The Preparation Of Levamlodipine Besylate And Its Tablet

Amlodipine is a kind of new drug in the treatment of cardiovascular disease developed by Pfizer. As a typical kind of the third generation 1,4-dihydropyridines calcium antagonists, amlodipine has been sold in many countries and areas in the world. It is very popular and one of the best-selling drugs to date because of it curative effect, consistant action and good safety.There are two steroisomers of Amlodipine, S-(-)-Amlodipine and R-(+)-Amlodipine. S-(-)-Amlodipine exhibts a effective action in the theatment of hypertension, and the R-(+)-isomer shows no effection or side effection. Therefore, Levamlodipine Besylate has a better therapeutic effect than racimic mixture and became the first chiral drug for the theatment of hypertension in the world.According to the literature, we studied the synthesis of Amlodipine using phthalic anhydride as starting material and then do the reaction such as protection of amino group, formation of ether group, amination, condensation, cycloaddition, deproection, ect. After that, Levamlodipine was prepared by chiral separation and diastereomeric salt formation. It needs to point out that the choice of the solvent has important influence on resolution. In our studies, we found a NMP solvent which showed the good resolution results. The target compound has been identified with IR,1H-NMR and optical purity conform to quality in the pharmacopoeia. With our optimization, the processes of chiral separation become more efficient and are suitable for large-scale production. We also did the prelimary studies on the process of levamolidipine bysylate tablets, which will help us to do the preparation for the industrial production.