吡唑[1,5-a]并吡啶-3-羧酸衍生物合成方法的改进

以取代吡啶为原料,在羟胺-O-磺酸的作用下,得到取代的N-氨基吡啶的硫酸盐,再通过1,3-偶极环加成反应,与丙炔酸乙酯生成吡唑[1,5-a]并吡啶-3-羧酸乙酯衍生物,然后在质量分数30%的NaOH水溶液作用下水解成酸。 该方法将取代的N-氨基吡啶的硫酸盐直接投入到下步反应,省去传统方法中将硫酸盐转化为碘盐的步骤,解决了碘盐不易析出的问题,并将取代的N-氨基吡啶硫酸盐和丙炔酸乙酯分别用水和二甲基甲酰胺溶解后再混合,增加了原料和K₂CO₃在体系中的溶解性,提高了产率。 本文成功合成了6种化合物(4a~4f),产率为88%~93%,该方法条件温和,后处理简单,成本低,是适合大规模生产的新工艺。

Improved Synthesis of Pyrazolo[1,5-a]pyridine- 3-carboxylic Acid Derivatives

Pyrazolo[1,5-a]pyridine-3-carboxylate derivatives were obtained from 1,3-dipolar cycloaddition reaction with ethyl propionate and N-aminopyridine sulfates synthesized by the reactions of substituted pyridines and hydroxylamine-O-sulfonic acid. They were further treated with 30%NaOH aqueous solution to give corresponding substituted pyrazolo[1,5-a]pyridine-3-carboxylic acid derivatives. In this method, N-aminopyridine sulfates were directly put into the next reaction, which eliminated the step of converting sulfate into iodine salt in the traditional method and solved the problem that the iodine salt was difficult to precipitate. N-aminopyridine sulfate and ethyl propionate were dissolved in water and N,N-dimethylformamide, respectively, and then mixed to increase the solubility of reactants. Six compounds(4a~4f) were successfully synthesized with yields of 88%~93%. The method is mild, easy to process and low cost as a new process for mass production.