Anti Tumor Drug Gefitinib(GEFITINIB) Study On The Synthesis Technology

Gefitinib(Irresa○R) is a kind of tyrosine kinase inhibitor of selective epidermal growth factor receptor, which was developed by Astra Zeneca. As the first protease inhibitors for the treatment of lung cancer, the medicine can be used for the treatment of the patients that previously received chemotherapy or are unsuitable for chemotherapy for locally advanced or metastatic non-small cell lung cancer(NSCLC) with good prospects. Accordingly, the study on the synthetic method of Gefitinib is of great importance.This study conducted a comprehensive analysis of the synthetic routes of Gefitinib that have been reported in the domestic and foreign literature, and summarize the advantages and disadvantages of each synthesis process. Combined with our company’s advantages, we chosed the inexpensive, readily available 4,5-dimethoxy-2-nitrobenzoic acid as the starting material. By using demethylation, esterification, side-chain alkylation, reduction, cyclization, chlorination, we firstly synthesized 3-chloro-4-fluoro aniline, which finally with,then, Gefitinib is prepared. This route avoids the use of the expensive materials of isovanillin or 6,7-dimethoxy-4-hydroxy-quinazoline, moreover, there is no hydroxyl protection or separation.The route can reduce the environmental pollution and simplified the conventional processes. A total of seven steps throughout the synthetic route, the total yield is more than 50%. The final product and the intermediates were fully characterized by 1H nuclear(NMR) and mass spectrum(MS), which confirmed that the obtained products are the expected medicines.