Synthesis of Axitinib

Axitinib,an inhibitor of vascular endothelial growth factor(VEGF) under investigation as an oncology drug,was developed by Pfizer and was approved by FDA in January 2012 with the trade name Inlyta.Based on the synthetic method of axitinib in one patent,we optimized and improved the existing process.For example,we used 2-mercapto-benzoic acid methyl ester in the coupling reaction instead of 2-mercaptobenzoic acid methyl amide to improve the yield and avoid using column chromatography in the reaction.In summary,In our designing route,axitinib was synthesized from 6-nitro-1 H-indazole by iodination,THP protection,Heck reaction,reduction,and then coupled with 2-mercapto-benzoic acid methyl ester,deprotection and ammonolysis with an overall yield of about 33.4%,which is higher than that of the reference(23.2%).The structures of axitinib and intermediates were confirmed by 1H-NMR and MS.