Department of Discovery Chemistry , MRL, Merck & Co., Inc. , Boston , Massachusetts 02115 , United States.
Org Lett. 2020 Jan 17;22(2):410-416. doi: 10.1021/acs.orglett.9b04117. Epub 2019 Dec 27.
Continuous flow has been used widely in process chemistry and academic settings for various applications. However, initial reaction discovery has generally remained "batch-exclusive" despite the existence of efficient, reproducible flow systems. We hereby disclose a workflow to bridge the gap between early medicinal chemistry efforts and process-scale development, showcased by the discovery and optimization of a metallaphotoredox-catalyzed cross-coupling between benzylic chlorides and aryl bromides, followed by two library syntheses of complex drug-like compounds.
连续流在工艺化学和学术领域得到了广泛应用，适用于各种不同的用途。然而，尽管已经存在高效、可重现的流动系统，最初的反应发现仍然普遍是“分批进行”的。在此，我们公开了一种工作流程，旨在弥合早期药物化学工作与工艺规模开发之间的差距，以苯甲酰氯和芳基溴化物之间的金属光氧化还原催化交叉偶联的发现和优化为例，并随后进行了两个复杂类似药物化合物库的合成。
