磷酸芦可替尼有关杂质的合成

Synthesis of Impurities Related to Luteinib Phosphate

根据磷酸芦可替尼原料药合成方法,分析了其合成过程中可能产生的潜在工艺杂质,并进行合成。以6-氯-7-氮杂嘌呤为起始原料经取代反应、偶联反应、水解反应分别进行了3个潜在杂质的合成,经高效液相色谱检测纯度均大于97.0%。合成方法具有制备过程简单、所得杂质纯度高等特点,化合物采用核磁共振氢谱碳谱,以及液质联用仪[2]进行了化学结构确证,结构确证数据与目标化合物相符,可以作为磷酸芦可替尼杂质对照品进行未知杂质的分析和鉴定。

Based on the synthesis method of the raw material of rutinib phosphate,potential process impurities that may occur during the synthesis process were analyzed and synthesized.Three potential impurities were synthesized using 6-chloro-7-azepurine as the starting material through substitution reaction,coupling reaction,and hydrolysis reaction.The purity was detected by high performance liquid chromatography to be greater than 97.0%.The synthesis method has the characteristics of simple preparation process and high impurity purity.The chemical structure of the compound was confirmed by nuclear magnetic resonance hydrogen spectrum and carbon spectrum,as well as liquid chromatography-mass spectrometry.The structural confirmation data is consistent with the target compound,and it can be used as a reference substance for the analysis and identification of unknown impurities in phosphorutinib.