BTK抑制剂BIIB068的多图谱合成

IF 2.1 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Chemical Papers Pub Date : 2023-07-18 DOI:10.1007/s11696-023-02951-9

Donghao Jia, Mingfang Gu, Xinyue Yu, Kunyang Yuan, Sixuan Wang, Mingzhang Guo, Ping Gong

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摘要

本文介绍了一种相对可行、经济、安全的多流程合成高效可逆BTK抑制剂BIIB068的方法。采用简单的亲核取代反应和氰基的绿色还原，经济地构建了2-氨基-4取代的嘧啶，突显了这一新工艺。所开发的方法提供了32%的总产率，HPLC纯度为99%。BIIB068的结构通过MS、IR、1H-NMR和13C-NMR得到了证实，一些中间体的结构也通过MS和1H-NMR得到了证实

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Multigram‑scale synthesis of BTK inhibitor BIIB068

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.

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来源期刊

Chemical Papers 化学-化学综合

CiteScore

3.90

自引率

4.50%

发文量

590

审稿时长

2.5 months

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.