Synthesis Process Of Hydrochloric Acid Dronedarone And Compound SR35021

Along with the social modernization process accelerating, people are under moregreater social pressure than before, the number of cardiovascular disease in our country isalso in increasing constantly.it has become a common disease which occurs frequently.Atrial fibrillation(AF) is not only a clinical common arrhythmia, but also a importantindependent risk factor of apoplexy, with the extension of human life, the incidence is inconstant growth.Dronedarone is an anti-arrhythmic drug developped by France’s Sanofi-Aventiscompany, which was approved in July of2009by the FDA for the first time in the UnitedStates. It applys to atrial fibrillation and atrial flapping patients rhythm of the heart control,maintains sinus rhythm and slows down the ventricular heart rhythm. CompoundSR35021is an metabolite of dronedarone after oral administration of the drug as well as amain related substances during dronedarone synthesis. France’s Sanofi-Aventis companyin the Australian health supervision departments about the varieties of public asessmentmentioned in the report. Debutyldronedarone is the only specified impurity, the limition ofit is no more than0.2%, and its synthesis route had not been reported in the literature.Based on the research and improvement of the synthetic process, we determined a suitablesynthesis route for industrialized production of dronedarone and debutyldronedaroneTake4-methoxybenzoyl chloride and2-butyl-5-nitrobenzofuran as raw material,through the Friedel-Crafts, demethylation, etherification, reduction, mesylation andhydrochloric ether salt by hydrochloric acid dronedarone. The total yield was32.9%andthe purity that measured by HPLC is greater than95%.With the reference synthetic route of dronedarone, debutyldronedarone wassynthesized by Friedel-Crafts reaction from4-methoxybenzoyl chloride and2-butyl-5-nitrobenzofuran, followed by demethylation, etherification, reduction andmesylation to give N-[2--butyl-3-[4-(3-chloropropoxyl)benzoyl]benzofuran-5-yl]methylsulfonamide, which was subjected to iodonation and amination with n-butylamine. Thetotal yield was23.6%and the purity that measured by HPLC is greater than98.7%.The chemical structure of Hydrochloric acid dronedarone and Debutyldronedaronewere confirmed by1H NMR,13C NMR, IR and MS.