JNJ-40411813合成工艺研究  

Improved synthetic process of JNJ- 40411813

作　　者：焦慎超[1] 夏文静[1] 刘丹[1] 赵临襄[1] 周宇[2] 柳红[2] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]中国科学院上海药物研究所,上海201203

出　　处：《中国药物化学杂志》2015年第4期291-294,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21372235)

摘　　要：目的研究抗精神分裂症药物JNJ-40411813合成新方法。方法以4-溴吡啶-2(1H)-酮为起始原料,经烷烃化、偶合及卤代3步反应得到目标产物JNJ-40411813。结果与结论目标化合物的结构经1H-NMR、13C-NMR、LRMS和HRMS等确证。该合成路线反应步骤简短,操作简便,反应条件温和,适合工业化生产。JNJ-40411813 （ also known as ADX71149 ）, a mGluR2 PAM （ positive allosteric modulator） and on phase Ⅱ clinical trials, was developed by Janssen Pharmaceuticals and Addex Therapeutics. In this paper, a new synthetic route has been established based on the related patent. In the patent, there are security risks or residual palladium ions in industrial production because hydrogen, strong alkali sodium tert-butoxide and palladium acetate are used. Using 4-bromopyridin-2-one（4）, different from the patent＇s, as the starting mate- rial, JNJ-40411813 was synthesized through three steps, including hydrocarbons, coupling reaction and halo- genated. First, 4-bromo-l-butylpyridin-2-one was reacted with 1-bromobutane under certain conditions to give intermediate 3. Intermediate 3 was coupled with 4-phenylpiperidine under the condition of CuI to give intermediate 2, which was chlorinated under the condition of N-chlorosuccinimide to give the target compound JNJ-40411813. Its structure was confirmed by 1H-NMR, laC-NMR,MS and HRMS. The improved process has several advantages over the patent＇s, such as mild conditions and simple operations. It is more suitable for industrial production.

关 键 词：JNJ-40411813 代谢型谷氨酸受体2正变构调节剂 工艺改进 

分 类 号：R914.5[医药卫生—药物化学]