达罗他胺中间体2-氯-4(1 H-吡唑-3-基)苯甲腈的合成工艺  

Synthesis Process of Darolutamide Intermediate 2-Chloro-4-(1H-pyrazole-3-yl)benzonitrile

作　　者：马卉芳 童悦 王荣繁 谢建伟 MA Huifang;TONG Yue;WANG Rongfan;XIE Jianwei(School of Medicine&Health Sciences,Guangzhou Huashang College,Guangzhou 511300,China;College of Chemistry and Bioengineering,Hunan University of Science and Engineering,Yongzhou 425199,China)

机构地区：[1]广州华商学院健康医学院,广东广州511300 [2]湖南科技学院化学与生物工程学院,湖南永州425199

出　　处：《合成化学》2024年第7期657-663,共7页Chinese Journal of Synthetic Chemistry

基　　金：广州华商学院校内导师制科研项目(2023HSDS37)。

摘　　要：2-氯-4(1H-吡唑-3-基)苯甲腈是抗前列腺癌新药达罗他胺的重要中间体片段。本文以4-溴-2-氯苯甲腈和1-(2-四氢吡喃基)-1 H-吡唑-5-硼酸频哪酯为原料,经Suzuki偶联和水解脱保护两步反应,在50 g反应规模时,以大于95%的总收率和大于99%的纯度得到2-氯-4(1H-吡唑-3-基)苯甲腈。该反应原料安全易得,产物分离简单,反应收率和产物纯度高,特别是第一步Suzuki偶联反应母液可循环套用,节约了Pd催化剂和生产成本,适合工业化生产。2-Chloro-4-(1H-pyrazole-3-yl)benzonitrile is an important intermediate fragment of the novel anti-prostate cancer drug darolutamide.In this paper,4-bromo-2-chlorobenzonitrile and 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole were chosen as the raw materials.Through Suzuki coupling and hydrolysis deprotection reactions,2-chloro-4-(1H-pyrazole-3-yl)benzonitrile was obtained with a total yield of over 95% and a purity of over 99% at the reaction scale of 50 g.The reaction has several advantages of safe and easy available raw materials,simple separation of the product,high yield and high product purity,especially the mother liquor of the Suzuki coupling reaction in the first step can be recycled,saving Pd catalyst and production costs,which are all suitable for industrial production.

关 键 词：达罗他胺中间体 2-氯-4(1H-吡唑-3-基)苯甲腈 SUZUKI偶联 工艺改进 合成 

分 类 号：O621.3[理学—有机化学] R914.5[理学—化学]