Modification Of Antiviral Arbidol On 6-Position

6-bromo-4-((dimethylamino)methyl)-5-hydroxy-1-methyl-2-((phenylthio)methyl)-1 H-in dole-3-carboxylic acid ethyl ester hydrochloride, also named arbidol, is an important non-nucleoside class of antiviral drug. Referring to the literature method, ethyl acetoacetate and benzoquinone were chosed as an starting material to synthesize arbidol via amination, Nenitzescu cylization, O-acylation reaction, bromination and Suzuki coupling reaction. In this study,6-position of Arbidol was structural modified and the synthetic conditions were optimized.The synthetic conditions were optimized such as the O-acylation reaction, bromination reaction, and Suzuki coupling reaction. The Suzuki coupling reaction between intermediate 4 and arylboronic acids was investigated. The results showed that the Suzuki coupling reaction occured on the benzyl bromide preferentially.Fifteen new target compounds (6a-6o) were obtained, which has the best antiviral compound 5 as the starting material, and introduced different kinds of aryl groups to its 6-position by the Suzuki coupling reaction. Their structures were characterized by'H NMR, 13C NMR and HRMS. The substrate scope was investigated with-CH3,-OCH3 as electron-donating functional group and-F,-Cl as electron-withdrawing group. While when there is-OH,-COCH3,-Br group in the structure, it is difficult to get the target molecule.