富马酸沃诺拉赞关键杂质2-氨基-5-(2-氟苯基)呋喃-3-腈的晶体结构研究  

Crystal Structure of 2-Amino-5-(2-fluorophenyl)furan-3-carbonitrile,a Key Impurity of Vonoprazan Fumarate

作　　者：牟红 齐阳历 巩艳青 陈晓文[2] 李建其[2] MOU Hong;QI Yangli;GONG Yanqing;CHEN Xiaowen;LI Jianqi(School of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620;Novel Technology Center of Pharmaceutical Chemistry,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203;Analysis and Testing Center,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]上海工程技术大学化学化工学院,上海201620 [2]中国医药工业研究总院上海医药工业研究院化学制药新技术中心,上海201203 [3]中国医药工业研究总院上海医药工业研究院分析测试中心,上海201203

出　　处：《中国医药工业杂志》2021年第10期1323-1328,共6页Chinese Journal of Pharmaceuticals

摘　　要：2-氨基-5-(2-氟苯基)呋喃-3-腈为钾离子竞争性酸阻滞剂富马酸沃诺拉赞合成中的关键工艺杂质,其结构中含碱性基团,但不易被酸洗去除。本研究采用溶剂挥发法培养得到2-氨基-5-(2-氟苯基)呋喃-3-腈的单晶,运用X射线单晶衍射技术对其立体结构进行解析。结果表明,该化合物晶态下分子间存在氢键作用,相邻分子间凭借一对氢键形成类二聚体结构,以范德华力和氢键维系其在空间的稳定排列,使结构中氨基氮原子的离子化能力降低,碱性下降,这可能是以简单酸洗方式难以去除该杂质的原因。2-Amino-5-(2-fluorophenyl)furan-3-carbonitrile is a key process impurity in the synthesis of vonoprazan fumarate as a potassium competitive acid blocker.Its structure contains basic groups,but it is not easy to be removed by acid washing.In this study,a single crystal of 2-amino-5-(2-fluorophenyl)furan-3-carbonitrile was cultivated by solvent evaporation method,and characterized by X-ray single crystal diffraction.The results showed that hydrogen bonds were presented in the crystalline state,two adjacent molecules formed quasi-dimer via a pair of hydrogen bonds between them,and the stable arrangement in space was maintained by van der Waals forces and hydrogen bonds.Therefore,the ionization ability of N atoms of amino group in the structure was reduced,and the alkalinity was decreased,which explained the possible reason why it was difficult for the impurity to be removed by simple washing with the acidic solution.

关 键 词：沃诺拉赞 工艺杂质 晶体培养 X射线单晶衍射 氢键 

分 类 号：R975.2[医药卫生—药品]