Research On Synthesis Of Elvitegravir

Elvitegravir,developed by Gilead Sciences,Inc.,is the first quinolones HIV integrase inhibitors.It was approved by the FDA for HIV/AIDS infection in 2012.This thesis discussed the synthetic technology of elvitegravir,taking 2,4-difluorobenzoic acid as the starting material,after 9 steps of iodination,acylation,condensation,addition,cyclization,esterification,Negishi coupling,hydrolysis,and substitution,and the overall yield was 54.2%.The purity of elvitegravir was 99.9%by HPLC.The structure was identified by 1H-NMR,13C-NMR?DEPT-135?IR,MS.The Form was identified by XRPD and DSC.The important intermediates 3,7,and 12 were crystallized and detected by HPLC with the purity 99.0%,99.8%,99.7%,and the structure was identified by 1H-NMR,IR,MS.The synthetic method of compound?,compound 12 with one-pot synthesis was simple and safe.This route had the advantages of cheap raw material,low production cost,environment friendly,high purity and suitable for industrial production.