{"title":"Multigram-scale synthesis of volasertib, an inhibitor of polo-like kinases in clinical evaluation","authors":"Kang Wang, Dong Zhao, Mingli Jin, Yuan Li, Lei Sun, Yanli Zhu, Chen Wang, Shuang Li, Yu Wang, Qianying Miao, Xiao Chen, Yanfang Zhao, Yunlei Hou","doi":"10.1007/s11696-024-03708-8","DOIUrl":null,"url":null,"abstract":"<div><p>This paper described the development of a practical, improved and efficient method for the multigram-scale synthesis of volasertib, an injectable bioavailable potent and selective inhibitor of PLK1. The key to this optimization was the design and development of a novel synthetic strategy, which involved the preparation of key intermediate 4-amino-<i>N</i>-{4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl}-3-methoxybenzamide (<b>W-5</b>) through nitro reduction sequence and (7<i>R</i>)-2-chloro-7-ethyl-7,8-dihydro-8-(1-methylethyl)-6(5<i>H</i>)-pteridinone (<b>W-11</b>) through reductive cyclization and <i>N</i>-methylation reaction. The developed process provided 46% overall yield, which enabled us to rapidly synthesize multi-gram quantities of volasertib in 99.42% purity.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":513,"journal":{"name":"Chemical Papers","volume":"78 17","pages":"8965 - 8977"},"PeriodicalIF":2.2000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Papers","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s11696-024-03708-8","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Engineering","Score":null,"Total":0}
引用次数: 0
Abstract
This paper described the development of a practical, improved and efficient method for the multigram-scale synthesis of volasertib, an injectable bioavailable potent and selective inhibitor of PLK1. The key to this optimization was the design and development of a novel synthetic strategy, which involved the preparation of key intermediate 4-amino-N-{4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl}-3-methoxybenzamide (W-5) through nitro reduction sequence and (7R)-2-chloro-7-ethyl-7,8-dihydro-8-(1-methylethyl)-6(5H)-pteridinone (W-11) through reductive cyclization and N-methylation reaction. The developed process provided 46% overall yield, which enabled us to rapidly synthesize multi-gram quantities of volasertib in 99.42% purity.
Chemical PapersChemical Engineering-General Chemical Engineering
CiteScore
3.30
自引率
4.50%
发文量
590
期刊介绍：
Chemical Papers is a peer-reviewed, international journal devoted to basic and applied chemical research. It has a broad scope covering the chemical sciences, but favors interdisciplinary research and studies that bring chemistry together with other disciplines.
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