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
高晨雪 1张鑫 1江璐 1李婷婷 1仝红娟2
作者信息
- 1. 陕西国际商贸学院 医药学院,陕西 咸阳 712046
- 2. 陕西国际商贸学院 医药学院,陕西 咸阳 712046;咸阳市分子影像与药物合成重点实验室,陕西 咸阳 712046
- 折叠
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 1H 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(PPh3)4 催化剂用量为n(Pd(PPh3)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%.
Abstract
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 1H 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(PPh3)4 catalyst n(Pd(PPh3)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Key words
Voxelotor/intermediate/Suzuki coupling reaction/condition optimization引用本文复制引用
基金项目
陕西省大学生创新创业训练计划(2023)(S202313123 015)
咸阳市分子影像与药物合成重点实验室项目(2021Q XNL-PT-0008)
出版年
2024
NETL
NSTL
维普
万方数据