Study On The Synthetic Process Of Imatinib Mesylate

Imatinib mesylate(Trade name: Gleevec),which is an inhibitor of Profein-fyrosihe Kinase,was developed by Novartis AG.The Food and Drug Administration(FDA)of United States has approved imatinib mesylate as the first-line drug for patients with chronic myeloid leukaemia(CML)of Philadelphia chromosome positive in accelerated phase,blast crisis,or after failure of interferon –a therapy on May,2001.Imatinib mesylate was also approved by FDA to treat gastrointestinal stromal tumor(GIST)on Jan,2002.Imatinib mesylate was deemed as blockbuster after three years on the market.This paper summarizes the action mechanism of new tumor drug of imatinib mesylate,clinical indications,synthetic route and preparation method of crystal form.The main purpose for this article is to solve pollution,difficult treatment for waste solvent and high cost for current process.The process of relative stability crystal ?-form was developed because the imatinib mesylate is a polycrystalline drug.The following synthetic route is designed.Imatinib mesylate was obtained through condensation,cyclization,hydrogenation and chlorination from 2-methyl-5-nitroanline as starting material in 55.5% overall yield.The reaction conditions were screened for each reaction and the optimal conditions such as reaction temperature,reaction time and addition ratio wereprovided.As well,the preparation method of crystal form was studied.Finally,? crystalform,available on the market,is successfullypreparedinacetoneand acetonitrileviadifferent solvents screening.Finally,the industrial manufacturing plan was established and confirmed based on process parameters,equipment selection and the engineering compatibility assessment between process and equipment.In addition,the quality and yields of imatinib mesylate reached the expected setting standard by conducting pilot production.