Research On The Synthesis Of Amisulpride And It’s Related Substance

With the rapid development of modern society, people are taking more and moresocial pressure, which leads to the increasing number of mental patients in China. Thereexists probably around7‰Patients with schizophrenia in China which is a commonpsychiatric disease. Amisulpride, a recently developed new generation of atypicalantipsychotics, then can be selected to act on dopamine DA2and DA3. Compared with thetraditional antipsychotics, amisulpride reveals an obvious treatment for patients withpositive and negative symptoms, due to its advantages of lower extra pyramidalside-effects and not raising the blood glucose.Through contrastive analysis of the synthetic route reported in the existing literatureand considering the feasibility in the industrialized production enlargement, the presentstudy determined to adopt a new synthetic route, which was synthesized from4-aminosalicylic acid by methylation, thiocyanation, ethylation, oxidation and hydrolysis reactionsto give4-amino-5-(ethylsulfonyl)-2-methoxybenzoic acid that was subjected tocondensation with (1-ethylpyrrolidin-2-yl) methanamine in the presence of triethylamineand ethyl chloroformate. Effect of reactant ratio, reaction temperature and time on all thereactions was examined in the optimization of each step. Methylation and introduction ofethylthio were mainly investigated in the present study. Simple and convenient fortreatment, the improved technological operation was suitable for industry. Additionally, asthe target compound and its intermediates being confirmed by1H NMR, MS and IR, thetotal yield amounted to44%. Moreover, to perform the quality control of Amisulpride,synthesis study was conducted on the related substances contained in Europeanpharmacopoeia.The target compound was also confirmed through1H-NMR and13C-NMR.