5-氯-2,4-二羟基吡啶的合成

目的:合成二氯嘧啶脱氢酶抑制剂5-氯-2,4-二羟基吡啶。方法:以丙二腈、原乙酸三甲酯、1,1-二甲氧基三甲胺为起始原料制备1,1-二氰基-4-(N,N-二甲基氨基)-2-甲氧基-1,3-丁二烯,经冰醋酸环合得2-羟基-4-甲氧基-3-氰基吡啶,再经硫酰氯氯化形成5-氯-4-甲氧基-3-氰基-2-(1H)-吡啶酮,经47%HBr水解得5-氯-2,4-二羟基吡啶。结果:合成了5-氯-2,4-二羟基吡啶,总收率为56%。结论:该工艺路线成本较低,反应条件温和,操作简便,容易实现工业化生产。

Studies on the synthesis of 5-chloro-2,4-dihydroxypyridine

Objective:To synthesize 5-chloro-2,4-dihydroxypyridine,a potent dihydropyrimidine dehydrogenase inhibitor.Methods: 5-chloro-2,4-dihydroxypyridine was synthesized by four steps from malononitrile,trimethyl orthoacetate and 1,1-dimethoxy-trimethylamine via condensation,cyclization,chlorination and hydrolysis reactions.Results: 5-chloro-2,4-dihydroxypyridine was synthesized in overall yield of 56.0%.Conclusion: The improved process has advantages of lower cost,mild reaction conditions,convenient work-up.It is suitable forindustrial production.