Research Towards The Improved Synthesis Of Nevirapine

As the first non-nucleoside reverse transcriptase inhibitor approved by FDA,nevirapine is widely used as an anti-AIDS drug.In consideration of its importance in treating AIDS,we did a detailed study on the synthetic process of this drug to reduce the costs of production.The first chapter presented current status of AIDS and summarized advances of the anti-AIDS drugs.Pharmacology and pharmacokinetics of Nevirapine were introduced and an overview of various synthetic routes for Nevirapine was given in this chapter.Through comprehensive analysis of these routes we integrated their advantages and designed an optimal route.The second chapter mainly studied the synthetic process optimized of Nevirapine.The second chapter mainly studied approaches to optimize the synthetic process of Nevirapine.(1)The feasibility of the designed synthetic strategies of the compound 3 was investigated.2-chloro-3-amino-4-methylpyridine was used as starting material to obtain compound 3 through the following three routes:(A)reacting with 2-Chloronicotinic acid ester;(B)reacting with 2-Chloronicotinic under the influence of DMAP/DCC system;(C)reacting with 2-Chloronicotinic under the influence of BTC/Et3 N system.Experimental results showed that routes A,B and C were all feasible to obtain the desired product.Meanwhile,the reaction conditions of routes A,B and C were repeatedly optimized,leading to 25%,33% and 71% yields respectively.(2)The feasibility of the designed synthetic strategies of Nevirapine was investigated.The starting material compound 3 transformed to compound 4 through the Cu I-Catalyzed Ullmann reaction with Cyclopropylamine.Then Nevirapine 1 was obtained through dehydrochlorination and cyclization of comound 4 by reacting with potassium tert-butoxide.After optimizing the reaction conditions,the total yield of this reaction reached 72%.In summary,through the experimental analysis and data comparison,we found a preferred synthetic route to obtain Nevirapine in 51% yield using 2-chloro-3-amino-4-methylpyridine as the original material.Compared with the original routes,the improved process was simpler,more environmentally friendly and could obtain higher yield.