Synthesis Of Multi - Target Receptor Tyrosine Kinase Inhibitor Malic Acid Sunitinib

Sunitinib(Sutent^TM, a multi-targeted receptor tyrosine kinase inhibitor, was developed by Pfizer. It was approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumour by the US Food and Drug Administration in January 2006.The relationship between vascularization and tumor and the research progress of angiogenesis inhibitors were reviewed. The research survey of novel small molecular multitargets receptor tyrosine kinases inhibitor Sunitinib was intruduced in detail in this thesis. Starting from methyl acetoacetate, Sunitinib was prepared by nitrosation and cyclization, followed by hydrolysis, decarboxylation, formylation, further hydrolysis, condensation with N,N-diethylethanediamine and condensation with 5-fluoroindolin-2-one. The total yield was 25%. （based on methyl acetoacetate）The process has advantages of simplified operation, high yield and purity, low cost and easy application and dissemination. The structure of the target molecule and some key intermediates were confirmed by ¹H-NMR and MS.