Study On The Synthesis Process Of Agomelatine

Agomelatine is an agonist of melatonin receptors and an antagonist of the serotonin 5-HT2 C receptor, It works in two ways, by stimulating the MT1 and MT2 receptors, which are normally activated by melatonin, and also by blocking the 5-HT2 C receptors, which are normally activated by the neurotransmitter 5-hydroxytryptamine(also called serotonin). Agomelatine was first authorised in the EU in February 2009. It is now marketed in all EU countries. It is believed to help relieve the symptoms of depression. It might also help to normalise the patient's sleep patterns.In this study, on the basis of analysis and assessment of several synthesis routes of agomelatine that had been reported, we designed an efficient, and productive process that consist of 4 steps. After laboratory experiment of the route we designed, we studied the temperature, time, solvent, and purification of each step. Critical control points were concluded. We combine the hydrogenation and acetylation steps into one step in step 3, so that we got the target compound in total yield 52.1%. The structure had been confirmed by UV, IR, NMR, MS. We also studied the relevant impurities which occurred in the process, and developed a robust quality control method.