雷西纳德的合成工艺研究  

Study on Synthesis Process of Lesinurad

作　　者：陈娇 苏文琴[1] 陈年根[1] 王跃梅 CHEN Jiao;SU Wen-qin;CHEN Nian-gen;WANG Yue-mei(School of Pharmacy,Hainan Medical University,Hainan Haikou 571199,China)

机构地区：[1]海南医学院药学院,海南海口571199

出　　处：《广州化工》2023年第2期102-104,共3页GuangZhou Chemical Industry

摘　　要：以1-环丙基萘-4-基异硫氰酸酯为起始原料,经亲核取代和环合、威廉姆逊反应、溴代和水解制得治疗痛风的药物的雷西纳德。中间体3的环合碱为碳酸钠,纯化溶剂为异丙醇。中间体4经甲苯纯化后,纯度可满足后续步骤的自由基反应。通过控制反应条件和精制条件,中间体5的纯度大大提高。采用氢氧化锂甲醇反应系统及丙酮精制,API的质量符合质量标准草案要求。整个合成步骤的收率为50.4%,HPLC检测纯度大于99.3%。与现有技术相比,本制备方法克服了文献所报道的制备工艺的缺点,特别是获得关键步骤溴代反应的关键参数。To study the preparation process of Lesinurad,a drug which was used in the treatment of arthrolithiasis,Lesinurad was synthesized from 1-cyclopropyl-4-isothiocyanatonaphthalene as the start material via nucleophilic substitution and cyclization,williamson reaction,bromination and hydrolysis.In the first step,the cyclic base of intermediate 3 was sodium carbonate and the purification solvent was isopropyl alcohol,and in the second step,the purity of intermediate 4 after purification by toluene could satisfy the free radical reaction in the following steps.In the third step,by controlling reaction conditions and refining conditions,the purity of intermediate 5 was greatly improved.In the last step,using lithium hydroxide methanol reaction system and acetone refining,API quality met the requirements of draft quality standard.The overall yield was 50.4%and HPLC purity was not less than 99.3%.The synthesis process of Lesinurad was completed and optimized,some drawbacks in the literatures were improved,and the key paramet-er of the bromination reaction was successfully obtained after repeated studies and experiments.

关 键 词：雷西纳德 合成 工艺优化 

分 类 号：R914[医药卫生—药物化学]