用于高效制备代谢型谷氨酸受体负变构调节剂（NAMs）的流动与间歇模式工艺的组合
A Combination of Flow and Batch Mode Processes for the Efficient Preparation of mGlu Receptor Negative Allosteric Modulators (NAMs).
作者信息
Dhanya Raveendra Panickar, Herath Ananda, Sheffler Douglas J, Cosford Nicholas D P
机构信息
Cancer Metabolism and Signaling Networks Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
出版信息
Tetrahedron. 2018 Jun 21;74(25):3165-3170. doi: 10.1016/j.tet.2018.03.068. Epub 2018 Mar 30.
Abstract
Benzodiazepinones are privileged scaffolds with activity against multiple therapeutically relevant biological targets. In support of our ongoing studies around allosteric modulators of metabotropic glutamate receptors (mGlus) we required the multigram synthesis of a β-ketoester key intermediate. We report the continuous flow synthesis of -butyl 3-(2-cyanopyridin-4-yl)-3-oxopropanoate and its transformation to potent mGlu negative allosteric modulators (NAMs) in batch mode.
摘要
苯二氮卓酮是一类具有针对多种治疗相关生物靶点活性的优势骨架。为支持我们正在进行的关于代谢型谷氨酸受体（mGlus）变构调节剂的研究，我们需要多克规模合成一种β-酮酯关键中间体。我们报道了3-(2-氰基吡啶-4-基)-3-氧代丙酸丁酯的连续流合成及其在间歇模式下转化为强效的mGlu负变构调节剂（NAMs）。
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