Study On The New Synthetic Route Of The Adjunct Of Severe Depression And The Anti-schizophrenia Epiperazole

Depression is a common mental illness.According to statistics from the World Health Organization,the number of people with depression in the world has exceeded 350 million.Depression has also surpassed cancer and become the second disease in the world.Major depression(MDD)is a severe manifestation of depression.The work and life of patients with severe depression are greatly affected.They cannot normally live and socialize,and even have a suicidal tendency.The suicide rate is as high as 15%.In China,only 2%of patients with depression have been treated systematically,but 200,000 patients chose to commit suicide,causing great harm to the social economy and population.Therefore,depression has become the second largest burden disease in China.Schizophrenia is another common mental disease in the world.The number of patients worldwide exceeds 23 million.The lifetime morbidity rate can be as high as 8‰ or even higher,and the recurrence rate is very high.The early mortality rate of patients is 2～3 of the general population Times.Schizophrenia seriously affects the work and life of patients,and is even closely related to disability.Therefore,schizophrenia patients are easily discriminated in society and human rights are easily violated.Schizophrenia can be treated with drugs and psychology,but 10%to 30%of patients still have ineffective treatment.The pathogenesis of depression and schizophrenia is very complicated,and there are many hypotheses,which are generally considered to be related to genetic inheritance,gender,neurohormone secretion,psychological and social environment,immunity,and intestinal microbes.Different antipsychotic drugs need to be developed for different pathogenesis.Brexpiprazole is an antipsychotic drug after aripiprazole prescribed by Otsuka Pharmaceutical.It seems to have a better treatment effect for the negative symptoms of schizophrenia,and it can also be used for adjuvant treatment of MDD,and the effect is quick.Therefore,epiperazole can be used as an adjunct to major depression and anti-schizophrenic drugs.This article summarizes the different synthesis routes of brexpiprazole in the original Otsuka patent and the currently published patents,comparing 7-hydroxyquinolin-2(1H)-one and benzo[b]thiophene compounds as The key intermediate is the pros and cons of the synthetic route of epiperazole,and finally the benzo[b]thiophene compound with more commercial research value is selected as the key intermediate.I also consulted a large number of documents and patents,studied the synthetic routes of different benzo[b]thiophene derivatives,and finally selected thiophene as the starting material,first synthesized the compound 4-hydroxybenzo[b]thiophene,and then 4-hydroxy Benzo[b]thiophene is the key intermediate to synthesize the final product epiperazole through coupling and other reactions.In this study,a new synthetic route of epiperazole was developed,which has the advantages of cheap raw materials and easy operation of the reaction steps.It has the potential to further expand the development and has good potential commercial value.