FTO抑制剂FB23衍生物的合成及晶体结构  

Synthesis and crystal structure of FB23 derivatives as FTO inhibitors

作　　者：唐文强 高艳蓉 李晓花[1,2] 党小琳 徐小娜[3] TANG Wen-qiang;GAO Yan-rong;LI Xiao-hua;DANG Xiao-lin;XU Xiao-na(School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis,Xianyang 712046,China;School of Pharmaceutical&Chemical Engineering,Xianyang Polyechnic Institute,Xianyang 712000,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西咸阳712046 [2]咸阳市分子影像与药物合成重点实验室,陕西咸阳712046 [3]咸阳职业技术学院医药化工学院,陕西咸阳712000

出　　处：《精细与专用化学品》2024年第9期36-39,共4页Fine and Specialty Chemicals

基　　金：陕西省教育厅2023年度一般专项科研计划项目(23JK0328);咸阳市分子影像与药物合成重点实验室项目(2021QXNL-PT-0008);陕西国际商贸学院“中药药效物质研究”创新团队资助项目(SSY18TD01)。

摘　　要：报道一种结构新颖的FB23衍生物——2-{[2,6-二氯-4-(3,5-二甲基异唑-4-基)苯基]氨基}-N-[2-(4-甲基哌嗪-1-基)乙基]苯甲酰胺(化合物1)的合成及晶体结构。以2-{[2,6-二氯-4-(3,5-二甲基异唑-4-基)苯基]氨基}苯甲酸(化合物2)和2-(4-甲基哌嗪-1-基)乙烷-1-胺(化合物3)为原料,通过酸胺缩合反应得到化合物1。优化并确定酸胺缩合反应的适宜条件为:N,N-二甲基甲酰胺为反应溶剂、物料比n(化合物3)∶n(化合物2)=1.1∶1、25℃反应3h,化合物1的收率达到89.7%(以化合物2计)。通过X-射线单晶衍射对产物的晶体结构进行表征,确定该晶体结构属于三斜晶系,P-1空间群,晶胞参数a=8.115(4)A,b=8.656(4)A,c=22.641(9)A,α=81.344(9)°,β=80.173(9)°,γ=65.833(8)°,体积V=1423.9(10)A^(3),单个晶胞中所含分子数Z=2,单个晶胞密度Dc=1.340g/cm^(3),衍射线波长μ=0.275mm-1,单胞中电子数目F(000)=608.0。The synthesis and crystal structure of a novel FB23 derivative 2-((2,6-dichloro-4-(3,5-dimethylisoxazol-4-yl)phenyl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)benzamide(compound 1)was reported.Using 2-((2,6-dichloro-4-(3,5-dimethylisoxazol-4-yl)phenyl)amino)benzoic acid(compound 2)and 2-(4-methylpiperazin-1-yl)ethan-1-amine(compound 3)as starting materials,the target compound(compound 1)was obtained by acid amine condensation reaction.The optimal conditions for the condensation reaction were optimized and determined as follows:N,N-Dimethylformamide as the reaction solvent,mole ratio n(compound 3)∶n(compound 2)=1.1∶1,the reaction was at 25℃for 3 h,under this reaction conditions,the yield of the product was 89.7%(calculated as compound 2).The crystal structure of the product was characterized by X-ray single crystal diffraction,and it was confirmed that the crystal structure belongs to the triclinic system,P-1 space group,cell parameters a=8.115(4)A,b=8.656(4)A,c=22.641(9)A,α=81.344(9)°,β=80.173(9)°,γ=65.833(8)°;Volume=1423.9(10)A^(3),number of molecules in single cell Z=2,single cell density D_(c)=1.340g/cm^(3),diffraction wavelengthμ=0.275mm^(-1),number of electrons in single cell F(000)=608.0.

关 键 词：FTO抑制剂 缩合反应 工艺优化 单晶结构 

分 类 号：TQ463[化学工程—制药化工]