Study On Synthesis Of 2-chloro-3-amino-4-methylpyridine

Nevirapine, firstly found by the Boehringer ?Ingelheim company in Germany, can be used to treat and control AIDS effectively. Considering it's importance on the treating to AIDS. we did detailed research on one important intermediate of this drug, 2-chloro-3-amino-4-methylpyridine,to realize the nationalized development of Nevirapine.In this paper we first did the overall and detailed review of the current status around the world especialy in China and recent developments in anti-AIDS drugs, and then did systematically summary of Nevirapine, the intermidiate 2-chloro-3-amino-4 -methylpyridine and many synthetic methods of 4,4-dimethoxy-2-butanon. In the princples of green environmental protection, lower costs and higher productivity, we summarized the best synthesis route and optimized every step upon the existing literature.(1) 4,4-dimethoxy-2-butanon was synthetized firstly. We obtained the best synthe -sis route through investigating the effect factors in every step, sodium formyl aceton was synthesized by methyl format and acetone and which ratio is 2.5:1.1:1.0 in 40℃, With sodium methoxide as catalyst, with methanol as solvent. 4,4-dimethoxy -2- butanon was synthesized by sodium formyl aceton and methanol which ratio is 1.0:1.3 in 30℃, with mesylate rescriptor as catalyst, The yield reached 75.9%.(2)Then 2-chloro-3-amino-4-methylpyridine was synthetized.The best synthesis route is:The preparation of 2-chloro-3-amino-4-methylpyridine starting from 4,4-dimethoxy-2-butanone and 2-cyanoacetamide, which reaction in 68℃,with Potassi-um hydroxide as catalyst, and get 2-hydroxyl-3 -cyano-4-methylpyridine; then chlorination by POCl3, get 2-chloro-3-cyano-4-methylpyridine; then hydrolysis by H2SO4, get 2-chloro-3-Amide-4-methylpyridine, last through Hoffman reaction and get the Target product 2-chloro-3-amino-4-methylpyridine. The yield reached 34.6%.In this paper we optimized the effect of proportions of raw materials, reaction time and temperature in every step, the total yield was greatly oimproved, which lay the foundation of the final synthesis of the target Nevirapine and comfirm the route that can be used in industrialization produce. And we also confirmed the structure of the compounds synthesized in every step by using the methods such as IR, MS, 1HNMR.