Study On Synthesis Of Nevirapine Intermediate CAPIC

AIDS is a difficult problem in the world,Treatment is mainly based on imported drugs,and treatment costs have always been at a high level.Therefore,domestic drug research and development institutions and manufacturers,in order to reduce the economic burden of AIDS patients and achieve the industrialized production of therapeutic drugs,Nevirapine is one of the therapeutic drugs in the literature.However,Naiweilaping’s production method has high requirements for its raw materials,technology,and equipment,and industrial production technology is very difficult.The synthesis technology of its key intermediate 2-chloro-3-cyano-4-methylpyridine(CAPIC)is especially the focus and difficulty of research.In this paper,an experimental study on the synthesis of Naiweilaping’s key intermediates was carried out,and the process optimization of the Knoevenagel condensation and closed-loop reaction of 4,4-dimethoxy-2-butanone and malonitrile was emphasized.The effects of reaction solvent,reaction ratio,reaction temperature and catalyst were studied in the experiment.The results show that:(1)With toluene as the solvent and MgO/HMCM-22 as the catalyst,it is possible to achieve large-scale industrial production of this product;(2)In the Knoevenagel condensation reaction,the optimal ratio of 4,4-dimethoxy-2-butanone and malonitrile should be a 1:1 molar mass reaction,capable of 4,The conversion rate of 4-dimethoxyl-2-butanone was increased to the maximum,saving costs and increasing production;(3)In the closed reaction,when the temperature is controlled at 50 ℃,the reaction reaches 90 min,and the reaction product can reach the maximum yield;(4)The concentrated sulfuric acid as a catalyst in the closed reaction can make the reaction more rapid,and the yield of the product is the largest at the ratio of concentrated sulfuric acid to the mixture of 10:7;(5)Through this route for mid-test amplification,each production of 1kg of products is 236.32 yuan less than the original process route,and the economic benefits are significant.