Study On Synthesis And Process Improvement Of Atypical Antipsychotic Drug SM-9018

SM-9018 is a serotonin antagonist and dopamine antagonist developed bySumitomo Pharmaceuticals for the potential treatment of schizophrenia and otherpsychoses. Its receptor binding profile and animal pharmacology resemble thoseof other atypical antipsychotic agents.First in my project, I succeed in obtaining desired productN-[4-{4-(1,2-benzisothiazol-3-yl)-1-piperaziny}butyl]cyclohexane-1,2-dicarboximide, monohydrochloride(SM-9018)according to the literature, whichhave been confirmed by ~1H-NMR spectra. For the purpose of large preparation,I'v improved the work-up operations, chromatographic separation is cancelled,instead of available operations in the factory , which has not much influence in theyield of target compound.Key reactions such as preparation of two amides and1-(1,2-benzisothiazol-3-yl)piperazine is paid much attention in. Particularly, Ihave investigated the reaction of 3-chloro-1,2-benzisothiazol with piperazine,discussing solvent factor and getting close result against to the literature. But thisis not a optimal date, I'd like to provide some reference in further research.