A New And Green Synthesis Process For The Anti-Cancer Drug Icotinib

Icotinib(Conmana ? Icotinib Hydrochloride)is a new anti-cancer drug,researched by Betta Pharmaceuticals Co.Ltd.It was approved for the treatment of EGFR mutations in patients with NSCLC by CFDA in June 2011.There are more than 7,0000 patients used the drugs since listing,so it's need to produce more than 8 tons API and use more than 65 tons Phosphorus oxychloride.The research designs to construct green chemistry production process instead of using Phosphorus oxychloride,including the following three research works:1.A new and green synthesis process for icotinib,including design of new synthetic approaches,remove toxic reagent Phosphorus oxychloride,the determination of starting materials and organic solvent,optimization of process parameters,and accumulation of process data and comprehensive analysis.2.Establish the quality standard of the new synthesis process for the starting materials,intermediates and API.Combine lab test with pilot plant test,formulate a feasible quality standard for the starting materials and intermediates,establish the standard and analysis method which suitable for API produced by new process.3.Research on the consistency in quality for API.Depending on < Technical Guideline for Making Post Approval Changes to Chemical Drug Products>,the comprehensive study on the quality and validation work of API were conducted.The study compared the quality of API and Icotinib tablets.The consistency in quality for API which produced before the process and after is confirmed.