Study Of Hydrochloric Acid Dronedarone Synthetic Process

With the rapid development of social modernization, the social pressure people bearing is growing, and the number of patients with cardiovascular disease is constantly increasing. Then, cardiovascular disease in recent years, has been listed as one of the top ten causes of death. Arrhythmia is common cardiovascular system disease. Atrial fibrillation (AF) is a common clinical arrhythmia, and is an important independent risk factors for stroke, the prevalence increase with the aging population, and has become the new public health problem. Now there is still not a safe and effective drug for the treatment of both high AF, so the study of antiarrhythmic drugs is much of our attention.Dronedarone is developed by Sanofi-Aventis as a new drug treatment of AF. Its chemical structure is similar with amiodarone, which is the standard drug treatment of atrial fibrillation with the same mechanism of action. They are both the potassium ion channel inhibitors, but dronedarone has fewer adverse reactions. Dronedarone is only anti-arrhythmic drug, which shows that it could significantly reduce atrial fibrillation/atrial flutter morbidity and mortality in patients with good market prospects.Through the synthesis process research and improvement, we identified a suitable synthetic route for industrial production of dronedarone. In this paper, we used the compound drone-5 as the starting material, via alkylation, reduction of nitro group, mesylation and salify to get dronedarone hydrochloride. And every step of the key routes were optimized. According to the process parameters chosen, the resulting dronedarone hydrochloride yield was stable, and quality met quality standards. Dronedarone hydrochloride chemical structure was confirmed by elemental analysis, UV absorption spectroscopy, infrared absorption spectroscopy, NMR and mass spectrometry.