4-羟基-2-(1H-吡唑-1-基)嘧啶-5-甲酸的合成工艺改进研究

Improvement of synthetic process of 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acid

目的对4-羟基-2-(1H-吡唑-1-基)嘧啶-5-甲酸的合成工艺条件进行优化。方法以1-脒基吡唑盐酸盐和乙氧基甲叉基丙二酸二乙酯为起始原料,在三乙胺催化下环合得到中间体4-羟基-2-(1H-吡唑-1-基)嘧啶-5-甲酸乙酯,再经过氢氧化锂在四氢呋喃–水混合溶剂中水解得到目标化合物。结果合成了目标化合物,经MS、1H-NMR确证了结构,质量分数为99.5%,本合成工艺的总收率为87%。结论该合成工艺具有操作简单、反应条件温和、成本低、产率和纯度较高等优点,适合工业化生产。

Objective To optimize the synthetic process of 4-hydroxy-2-(1 H-pyrazol-1-yl)-pyrimidine-5-carboxylic acid. Methods 1-Amidinopyrazole hydrochloride and diethylethoxymethylenemalonate were used as starting materials to obtain the intermediate ethyl 4-hydroxy-2-(1 H-pyrazol-1-yl)pyrimidine-5-carboxylate through cyclization catalyzed by triethylamine. The title compound was obtained via hydrolysis by lithium hydroxide in mixed solvent of water and tetrahydrofuran. Results The target compound was synthesized and characterized by MS and 1 H-NMR. And the purity was 99.5%, and the total yield of this route was 87%. Conclusion The synthetic process has the advantages of simple operations, mild reaction conditions, low cost, high yield and purity, and is more suitable for industrial production.