Research On The Synthetic Process Of Imatinib Base

Imatinib Base is an important drug for the treatment of chronic myeloid leukemia,so research on the synthetic process of Imatinib Base plays a significant role.The intelligent and service-oriented production will be the future of the chemical industry,so the research on rapid and convenient synthesis of drugs is very important.Microwave technology has been applied in the synthesis of many drugs,because of its high energy utilization and sensitivity,therefore,the study on microwave-assisted synthesis of Imatinib Base may have some positive effect.In this thesis,the imatinib base was obtained via nine steps with a total yield of 33%,employing compound 2-amino-4-nitrotoluene?p-methylbenzonitrile as the starting material.The specific route is as follows: the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine intermediate was obtained from 2-amino-4-nitrotoluene through the reaction with cyanamide to give guanidine intermediate,condensation,cyclization and reduction of the nitro group;the 4-(4-methylpiperazine)benzoyl chloride intermediate was acquired through benzylic bromination of the p-methylbenzonitrile,benzylic substitution with N-methylpiperazine,hydrolysis of the nitrile group,acylation of the acid;finally,the imatinib base was synthesized through the amidation reaction.It is worth mentioning that several improvements have been made in the reaction of the benzylic bromination,the reduction of the nitro group and the amidation reaction.Furthermore,the new microwave-assisted synthetic process of imatinib base was studied,which make Imatinib base product directly from 3-acetylpyridine via four steps with a total yield of 31%.The microwave technology was applied to the condensation,the cyclization,the reduction,and the amidation reaction.Additionally,the optimized conditions for each step have been explored.Nuclear Magnetic Resonance(NMR)and Liquid Chromatography-Mass Spectrometry(LC-MS)have been used to identify the structure and the purity of the corresponding compounds.