钯催化2,3-二氢咪唑并[2,1-b]噁唑类衍生物的合成  

Synthesis of 2,3-dihydroimidazo[2,1-b]oxazole derivatives by palladium catalysis

作　　者：任成 张加强 陈诚 陆群[1] REN Cheng;ZHANG Jiaqiang;CHEN Cheng;LU Qun(School of Life Science and Engineering,Southwest Jiaotong University,Sichuan,610031 P.R.China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031

出　　处：《华西药学杂志》2021年第2期113-117,共5页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81771692)。

摘　　要：目的建立一种高效、温和的钯催化构建2,3-二氢咪唑并[2,1-b]噁唑杂环的方法,并用于合成CGI-7341及PA-824关键中间体。方法通过条件筛选,以Pd2(dba)3为催化剂、John Phos为配体、Cs2CO3为碱、甲苯和四氢呋喃为溶剂、反应温度为90℃的最优反应条件,制备一系列2,3-二氢咪唑并[2,1-b]噁唑类衍生物。结果与讨论成功构筑了2,3-二氢咪唑并[2,1-b]噁唑杂环,并制备了一系列衍生物,有效地提高了CGI-7341及PA-824关键中间体的收率,为快速高效构建含硝基咪唑并噁唑类抗结核化合物奠定了基础。OBJECTIVE To develop an efficient and mild palladium-catalyzed method for the construction of 2,3-dihydroimidazo[2,1-b]oxazole heterocycles,and to synthesize of CGI-7341 and PA-824 key intermediate.METHODS A series of 2,3-dihydroimidazoles were prepared by using this catalytic system:Pd2(dba)3 as the catalyst,John Phos as the ligand,Cs2 CO3 as the base,toluene and tetrahydrofuran as solvents,and the reaction temperature at 90℃.RESULTS and CONCLUSION The 2,3-dihydroimidazo[2,1-b]oxazole heterocycle was successfully constructed,and a series of derivatives were prepared,which effectively improved the yield of key intermediates of CGI-7341 and PA-824.The current study has laid the foundation for the rapid and efficient construction of nitroimidazole-containing antituberculosis compounds.

关 键 词：钯催化 CGI-7341 PA-824 抗结核 硝基咪唑 噁唑杂环 耐多药结核病 广泛耐药性结核病 

分 类 号：R914[医药卫生—药物化学]