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Research On Synthesis Of Agomelatine

Posted on:2015-02-08Degree:MasterType:Thesis
Country:ChinaCandidate:Y F ZhuangFull Text:PDF
GTID:2251330425985326Subject:Pharmaceutical Engineering
Abstract/Summary:PDF Full Text Request
Agomelatine, an agonist of melatoninergic system receptors and the5-hydroxytryptamine2C (5-HT2c) receptor antagonist, is the first melatonergic antidepressant and effective in the treatment of depression. Moreover, it can also improve sleep parameters. A variety of synthetic methods of agomelatine were reported. There are advantages as well as disadvantages with these methods. Based on the analysis of the previous routes, we developed a new synthesis of agomelatine in this paper. In this new route,(7-methoxy-3,4-dihydro-l-naphthyl) acetonitrile was selected as the starting material, followed by dehydrogenation with2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to afford (7-methoxy-l-naphthyl) acetonit-rile in the yield of91%. Then, the obtained (7-methoxy-l-naphthyl) acetonitrile was subjected with potassium borohydride and Nickel chloride hexahydrate to give2-(7-methoxynaphth-1-yl) ethylamine in the yield of81%. Finally, agomelatine was obtained through acetylation reaction in the yield of93%and an overall yield of65%. Fewer steps, simple operation, mild reaction conditions, no use of special equipment, lower cost, and more suitable for industrial production make this new route more practical.The structures of the intermediates and products were confirmed by1H NMR and MS. Better technical parameters of synthesizing agomelatine were obtained from the discussion of factors of affecting the reactions above.
Keywords/Search Tags:antidepressant, melatonin, agomelatine, dehydrogenation, synthesis
PDF Full Text Request
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