An Alternative Synthetic Route to Rilzabrutinib via an E-Configured Cyanoacrylic Acid Intermediate
文献类型：期刊论文
| 作者 | Wei, Daibao1; Guo, Jinbo4; Zhu, Fuqiang2; Bonku, Emmanuel Mintah1; Sun, Changliang2; Yang, Peng4; Qin, Hongjian2; Shen, Jingshan1,3 |
| 刊名 | JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2025-10-24 |
| 卷号 | 90期号:42页码:15065-15073 |
| ISSN号 | 0022-3263 |
| DOI | 10.1021/acs.joc.5c02058 |
| 英文摘要 | In this manuscript, an alternative route of synthesis for making rilzabrutinib via amide formation was described. The two segments for the amide formation are pyrazolopyrimidine-piperidine 20 and E-cyanoacrylic acid 21. The yield of 20 from Mitsunobu reaction was doubled compared with the existing route, and the Knoevenagel-derived 21 exhibited exclusive E-configuration. This route, in contrast to Sanofi's medicinal chemistry route, avoids Z/E isomer separation, achieves a 20-fold increase in overall yield, and improves sustainability through transition-metal-free catalysis and chromatography-free intermediates purification. |
| WOS关键词 | KINASE INHIBITOR ; DISCOVERY ; POTENT ; AMIDE |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[XDA12050411] ; Special Foundation of Chinese Academy of Sciences for strategic pilot technology[18431907100] ; Science and Technology Commission of Shanghai Municipality |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001591560300001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321672]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Qin, Hongjian; Shen, Jingshan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Topharman Shanghai Co Ltd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wei, Daibao,Guo, Jinbo,Zhu, Fuqiang,et al. An Alternative Synthetic Route to Rilzabrutinib via an E-Configured Cyanoacrylic Acid Intermediate[J]. JOURNAL OF ORGANIC CHEMISTRY,2025,90(42):15065-15073. |
| APA | Wei, Daibao.,Guo, Jinbo.,Zhu, Fuqiang.,Bonku, Emmanuel Mintah.,Sun, Changliang.,...&Shen, Jingshan.(2025).An Alternative Synthetic Route to Rilzabrutinib via an E-Configured Cyanoacrylic Acid Intermediate.JOURNAL OF ORGANIC CHEMISTRY,90(42),15065-15073. |
| MLA | Wei, Daibao,et al."An Alternative Synthetic Route to Rilzabrutinib via an E-Configured Cyanoacrylic Acid Intermediate".JOURNAL OF ORGANIC CHEMISTRY 90.42(2025):15065-15073. |
入库方式： OAI收割
来源：上海药物研究所
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