沃塞洛托中间体2-(1-异丙基-1H-吡唑-5-基)烟酸乙酯的合成  

Synthesis of Voxelotor intermediate ethyl 2-(1-isopropyl-1H-pyrazol-5-yl)nicotinate

作　　者：高晨雪 张鑫 江璐 李婷婷 仝红娟 GAO Chen-xue;ZHANG Xin;JIANG Lu;LI Ting-ting;TONG Hong-juan(School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis,Xianyang 712046,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

出　　处：《化学工程师》2024年第1期1-3,共3页Chemical Engineer

基　　金：2023年陕西省大学生创新创业训练计划项目(S202313123015);咸阳市分子影像与药物合成重点实验室项目(2021QXNL-PT-0008)。

摘　　要：本文报道沃塞洛托中间体2-(1-异丙基-1H-吡唑-5-基)烟酸乙酯(1)的合成方法。以2-氯烟酸乙酯(2)与1-异丙基吡唑-5-硼酸频哪醇酯(3)为原料,在Pd(PPh3)4催化作用下,发生Suzuki偶联反应得到产物(1)。产物结构经^(1)H NMR和MS表征。随后,对影响产物收率的因素进行了考察,确定适宜的反应条件为:物料比n_((3))∶n_((2))=1.2∶1、Pd(PPh_(3))_(4)催化剂用量为n_((Pd(PPh_(3))_(4)))∶n_((2))=0.04∶1、反应溶剂为二氧六环/水混合物、反应温度为100℃,在该反应条件下,产物收率达到75.7%。The synthesis of Voxelotor intermediate ethyl 2-(1-isopropyl-1H-pyrazol-5-yl)nicotinate(1)was reported.The Suzuki coupling reaction of ethyl 2-chloronicotinate(2)with 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(3)was catalyzed by Pd(PPh3)_(4).The structure of the product was characterized by ^(1)H NMR and MS.Subsequently,the factors affecting the yield of the product were investigated,the optimum reaction conditions were as follows:n_((3))∶n_((2))=1.2∶1,the dosage of Pd(PPh_(3))_(4) catalyst n_((Pd(PPh_(3))_(4)))∶n_((2))=0.04∶1,the reaction solvent was the mixture of dioxane and water,and the reaction temperature was 100℃,under this reaction conditions,the yield of product was up to 75.7%.

关 键 词：沃塞洛托 中间体 SUZUKI偶联反应 条件优化 

分 类 号：TQ463[化学工程—制药化工]