{"title":"Multigram‑scale synthesis of BTK inhibitor BIIB068","authors":"Donghao Jia, Mingfang Gu, Xinyue Yu, Kunyang Yuan, Sixuan Wang, Mingzhang Guo, Ping Gong","doi":"10.1007/s11696-023-02951-9","DOIUrl":null,"url":null,"abstract":"<div><p>This paper describes the development of a relatively feasible, economic, and safe method for the multigram-scale synthesis of <b>BIIB068,</b> an efficient reversible BTK inhibitor<b>.</b> The new process is highlighted by an economical construction of a 2-amino-4 substituted pyrimidine employing a simple nucleophilic substitution reaction and a green reduction of the cyano group. The developed process provided an overall yield of 32%, with an HPLC purity of 99%. The structure of <b>BIIB068</b> was confirmed by MS, IR, <sup>1</sup>H-NMR, and <sup>13</sup>C-NMR, and the structures of some intermediates were confirmed by MS and <sup>1</sup>H-NMR.</p><h3>Graphical abstract</h3>\n <figure><div><div><div><picture><img></picture></div></div></div></figure>\n </div>","PeriodicalId":55265,"journal":{"name":"Chemical Papers","volume":"77 11","pages":"6471 - 6481"},"PeriodicalIF":2.1000,"publicationDate":"2023-07-18","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/s11696-023-02951-9","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
This paper describes the development of a relatively feasible, economic, and safe method for the multigram-scale synthesis of BIIB068, an efficient reversible BTK inhibitor. The new process is highlighted by an economical construction of a 2-amino-4 substituted pyrimidine employing a simple nucleophilic substitution reaction and a green reduction of the cyano group. The developed process provided an overall yield of 32%, with an HPLC purity of 99%. The structure of BIIB068 was confirmed by MS, IR, 1H-NMR, and 13C-NMR, and the structures of some intermediates were confirmed by MS and 1H-NMR.
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
