克拉屈滨的合成工艺改进及其主要杂质研究

Improved synthesis of cladribine and research on its major impurity

目的:改进克拉屈滨的合成工艺,控制生成的主要杂质,提高收率与质量,获得良好的生产工艺。方法:以2-氯-6氨基嘌呤和2-脱氧-D-核糖为原料,对6步反应条件进行优化与改进,合成克拉屈滨,对克拉屈滨的主要杂质进行鉴别,研究其产生原因与控制方法。结果:产品质量及收率得到提高,质量符合USP35标准,收率达到30.2%,主要杂质的结构经MS,1HNMR,13CNMR确证为嘌呤二聚体核苷类似物。结论:优化后工艺收率高,产品质量好,操作简便,适合工业化生产。

Objective： To improve the synthesis of cladribine and investigate its major impurity. Methods：After the conditions of six-step process had been optimized and modified,cladribine was synthesized from 2-chloroadenine and 2-deoxy-D-ribose,and the major impurity of cladribine was studied. Results： The quality and yield of cladribine were improved. The quality met USP35 specifications,and the yield was up to 30. 2%. The major impurity was analogues of purine nucleoside dimmers,and the structure was identified by MS,1HNMR and13 CNMR. Conclusion： The improved process is easy to operate with high yield and quality,and suitable for industrial production.