[摘要]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。

    [关键词] 5-氯-2,4-二羟基吡啶；抗癌药；药物合成

    [中图分类号]R605 [文献标识码]A [文章编号]1673-7210(2007)06(b)-014-02

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

    SHA Mei，XU Wei，YU Yu-yan，ZHANG Shu-ling

    (Department of Pharmacy，Fujian College of Traditional Chinese Medicine, Fuzhou 350108,China)

    [Abstract] 0bjective: 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 ......