Darolutamide结构片段5-乙酰基-1H-吡唑-3-羧酸的绿色合成工艺  

Green synthesis process of darolutamide structural fragment 5-acetyl-lH-pyrazole-3-carboxylic acid

作　　者：马卉芳 童悦 王荣繁 谢建伟 MA Hui-fang;TONG Yue;WANG Rong-fan;XIE Jian-wei(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：《化学研究与应用》2025年第2期505-512,共8页Chemical Research and Application

基　　金：广州华商学院校内导师制科研项目(2023HSDS37)资助。

摘　　要：以3-丁炔-2-醇为起始原料,经氧化、环化和水解三步反应,在百克级产物规模下,以大于70%的总收率和大于99%的纯度制备得到抗前列腺癌药darolutamide的重要结构片段5-乙酰基-1H-吡唑-3-羧酸。通过单因素实验对每步反应的关键参数均进行了优化,得到了一条快速、高效的合成工艺路线。在第一步氧化过程中,采用2-碘酰基苯甲酸(IBX)作为氧化剂,反应结束后,通过简单过滤即可回收2-碘苯甲酸用于IBX的再生产,滤液则直接用于下一步反应;第二步环化反应不需要添加任何催化剂即可获得很好的实验结果;三步反应及后处理中,只用到丙酮和乙醇两种有机溶剂,减少了污染并可有效控制生产成本。该方法具有原料安全易得、产物分离简单、反应收率和产物纯度高,具有良好的工业化前景。By using 3-butyne-2-ol as the starting material,5-acetyl-1H-pyrazole-3-carboxylic acid,as an important structural fragment of the anti-prostate cancer drug darolutamide,was prepared through three steps of oxidation,cyclization,and hydrolysis reactions with a total yield of over 70%and a purity of over 99%under the reaction scale of 100 g.The key parameters of each reaction step were optimized by single factor experiments and a fast and efficient synthesis process route was obtained.In the first step of oxidation process,2-iodoxybenzoic acid(IBX)was used as the oxidant.After the reaction was completed,2-iodobenzoic acid could be recovered through simple filtration for the reproduction of IBX,and the filtrate was used directly for the next step reaction.The second step of cyclization reaction didn't require the addition of any catalyst to obtain good experimental results.Moreover,only two organic solvents,acetone and ethanol,were used in the three-step reaction process,benefitting to reducing pollution and effectively controlling production costs.The present method had several advantages of safe and easy available raw materials,simple separation of the product,high yield and high product purity,which were all suitable for industrial production.

关 键 词：达罗他胺 5-乙酰基-1H-吡唑-3-羧酸 2-碘酰基苯甲酸 工艺改进 绿色制备工艺 

分 类 号：O626.2[理学—有机化学]