The Research For The Synthesis Of Antidepressant Agomelatine

With the increasing work pressure and accelerated pace of modern life,depression has become a multiple mental disease, seriously harm to people’s physical and mental health and reducing the quality of people’s life.The novel antidepressant, Agomelatine, which chemical name is N-[2-(7-Methoxy-1-naphthalenyl)ethyl]acetamide, an agonist of melatonin MT1、MT2receptor and the 5-hydroxytryptamine2c(5-HT2c)receptor antagonist, is the first melatonergic antidepressant developed by Servier company of French. It has an unique pharmacological mechanism of Antidepressant, anxiolytic and regulate the sleep-wake cycle, with fast working, fewer adverse reactions, higher securi-ty, making a breakthrough in the treatment of depression.A new synthetic route which is more available and more economical was designed, based on a large number of relevant literature and given a scientific evaluation for the present synthesis methods of agomelatine reported by home and abroad. The route used industrial grade 1-amino-7- naphthol as starting material, by diazotization, Sandmeyer reaction to get 1-bromine-7-naphthol in the yield of 61.4%.With dimethylsulfate methylation to get 7- methoxy-1- bromo naphthalene in the yield of 91.2%. Then reacted with bromine acetonitrile to obtain the key intermediate of 7- methoxy-1-naphthyl acetonitrile in the yield of 55.8%. Finally, agomelatine was obtained through Sodium borohydride and acetylation reaction in the yield of 90.4%.This synthetic route broke through the patent restrictions, get rid of the present process which generally used expensive 7-methoxy-1-tetralone as starting material, prepared the key intermediate 7-methoxy-1- naphthylacetonitrile by DDQ or Pd-C. But this route directly reacted with bromine acetonitrile to get the key intermediates. The systhesis route which cost of economic, simple and feasible to make a certain industrial value.In this paper all the compound structure were confirmed by 1H-NMR and MS.