特立氟胺烯醇酯的合成研究

Study on the Synthesis of Teriflunomide Enol Ester

在研究特立氟胺酯类前药过程中发现了一些异常现象:当特立氟胺与丁二酸酐反应时,在中性和弱碱性条件下生成酰胺交换产物,在强碱性条件下无产物生成;当特立氟胺与高活性的乙酰氯反应时,在弱碱性条件下也发生了类似的酰胺交换反应,而在强碱性条件下可得到乙酰烯醇酯产物,不过该酯化产物稳定性差。这表明,特立氟胺烯醇羟基上难以发生酯化反应,且酯化产物不稳定。本文对上述异常现象进行了分析讨论。

In process of studying the esterification of teriflunomide,some interesting phenomena were found under common esterification conditions.When teriflunomide reacted with the succinic anhydride under neutral or weak alkaline conditions,an unexpected product from exchanging of amide was obtained,while no products were formed under strong basic condition.When teriflunomide reacted with the reactive acyl chloride under weak alkaline condition,the similar unexpected amide exchange reaction was occurred,however,the corresponding enol ester could be yielded under strong basic conditions,but its stability was poor.These results showed that the esterification of the enol hydroxyl group in teriflunomide was difficult and its product was extremely unstable.The mentioned unexpected phenomena were analyzed and discussed.