摘要
为更好地控制泊沙康唑原料药的质量,设计合成了2个潜在的工艺杂质,分别是4-[4-[4-[4-[[(3R,5R)-5-[2-氟-4-(1,2,4-三唑基)苯基]-5-(1,2,4-三唑-1-基甲基)氧杂戊环-3-基]甲氧基]苯基]哌嗪-1-基]苯基]-2-[(2S,3S)-2-羟基戊-3-基]-1,2,4-三唑-3-酮(有关物质A)和4-[4-[4-[4-[[(3R,5R)-5-(2,4-二氟苯基)-5-(1,3,4-三唑-1-基甲基)氧杂戊环-3-基]甲氧基]苯基]哌嗪-1-基]苯基]-2-[(2S,3S)-2-羟基戊-3-基]-1,2,4-三唑-3-酮(有关物质B)。文章首次报道了泊沙康唑潜在有关物质A和B的合成路线,且纯度均≥95.0%。其化学结构经NMR、HRMS确证与目标化合物的结构一致,可作为泊沙康唑质量研究的对照物。
In order to perform the quality control of posaconazole,the two process impurities were synthesized,namely 4-[4-[4-[4-[[(3R,5R)-5-[2-fluoro-4-(1H-1,2,4-triazol)phenyl]-5-(1H-1,2,4-triazol-1-ylmethy1)-3-furanyl]-methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(2S,2S)-2-hydroxy-3-pentyl]-1,2,4-triazol-3-one(the related substance A)-and 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,3,4-triazol-1-ylmethy1)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(2S,2S)-2-hydroxy-3-pentyl]-1,2,4-triazol-3-one(the related substance B).The synthesis routes of the related substance A and the related substance B were first reported.The structures of the products were confirmed by ~1H NMR and HRMS,which could be used as the references for quality control of posaconazole.
作者
蔡建光
林塘焕
张衡
陈延安
陈立茹
CAI Jianguang;LIN Tanghuan;ZHANG Heng;CHEN Yan'an;CHEN Liru(Zhejiang Hisun Pharmaceutical Co.,Ltd.,Taizhou 318000)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2022年第4期486-490,共5页
Chinese Journal of Pharmaceuticals
关键词
泊沙康唑
质量控制
有关物质
合成
posaconazole
quality control
related substance
synthesis
作者简介
蔡建光(1988-),男,硕士,从事药物合成研究。E-mail:jgcai@hisunpharm.com。
