Study On Preparation Technology Of Dabigatran Etexilate Mesylate

Objective The aims of this paper was to investigate the synthetic process of Dabigatran etexilate mesylate,and to get a reasonable route for industrial production.Methods The existing Dabigatran etexilate mesylate process is carried out optimized.The final product was synthesized from 4-(methylamino)-3-nitrobenzoic acid through eight steps including acyl chlorination,acylation,reduction,cyclization,alcoholysis,ammonolysis,acylation and salifying.MS and 1H-NMR were used to confirm structures of Dabigatran etexilate mesylate and its intermediates,and the HPLC method was used to determine the purity of the final compound.Results The synthetic process of Dabigatran etexilate mesylate was studied and the final product was obtained with a high total yield of 43.4%.Structures of Dabigatran etexilate mesylate,as well as its intermediates,were confirmed by MS and 1H-NMR,and the purity of the final compound was 99.7% as determined by HPLC.Conclusions The optimized process has the advantages of mild reaction conditions,simple operations,etc.,which made it suitable on an industrial scale.