Application of Biocatalytic Reductive Amination for the Synthesis of a Key Intermediate to a CDK 2/4/6 Inhibitor,Organic Process Research & Development

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Application of Biocatalytic Reductive Amination for the Synthesis of a Key Intermediate to a CDK 2/4/6 Inhibitor
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2021-09-03 , DOI: 10.1021/acs.oprd.1c00255
Shengquan Duan ₁ , Daniel W. Widlicka ₁ , Michael P. Burns ₁ , Rajesh Kumar ₁ , Ian Hotham ₁ , Jean-Nicolas Desrosiers ₁ , Paul Bowles ₁ , Kris N. Jones ₁ , Lindsay D. Nicholson ₁ , Michele T. Buetti-Weekly ₁ , Lu Han ₁ , Jeremy Steflik ₁ , Eric Hansen ₁ , Cheryl M. Hayward ₁ , Holly Strohmeyer ₁ , Sébastien Monfette ₁ , Scott C. Sutton ₁ , Christopher Morris ₁

Affiliation

Biocatalytic reductive amination catalyzed by engineered imine reductase (RedAms) is a new and powerful tool for the synthesis of substituted chiral amines. Herein, we describe a streamlined synthesis of compound 3, a key intermediate to a CDK 2/4/6 inhibitor 1, relying on the enzymatic reductive amination of a hydroxyketone to introduce the chiral secondary amine with high diastereoselectivity. The improved synthesis of the hydroxyketone precursor by a titanium-catalyzed reductive cyclization and the process development for two S_NAr reactions en route to 3 are also presented.

中文翻译：

生物催化还原胺化在 CDK 2/4/6 抑制剂关键中间体合成中的应用

工程亚胺还原酶（RedAms）催化的生物催化还原胺化是合成取代手性胺的一种新的强大工具。在此，我们描述了化合物 3 的流线型合成，化合物3是 CDK 2/4/6 抑制剂1的关键中间体，依靠羟基酮的酶还原胺化来引入具有高非对映选择性的手性仲胺。_{还介绍了通过钛催化还原环化改进的羟基酮前体合成和两个 S N} Ar 反应过程中的工艺开发3。

更新日期：2021-09-03

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