Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction,Organic Process Research & Development

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Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2019-11-27 , DOI: 10.1021/acs.oprd.9b00421
Patrick Cerfontaine ₁ , Frank Driessens ₁ , Marie-France Deltent ₁ , Sylvain Petit ₁

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Herein we describe the practical synthesis of a novel VLA-4 antagonist 1 as a potential treatment for multiple sclerosis. The key step is based on the Povarov reaction of an imine with an alkene to access a tetrahydroquinoline intermediate, leading to the corresponding quinoline core after an oxidative aromatization step. The development of the synthesis of 1 led to decreased complexity and the elimination of chromatographic purifications. These improvements were demonstrated at scale by the production of 32 kg of 1 in high yield with excellent purity.

中文翻译：

通过Povarov反应有效合成多公斤VLA-4拮抗剂

在这里，我们描述了新型VLA-4拮抗剂1的实用合成，作为多发性硬化症的潜在治疗方法。关键步骤基于亚胺与烯烃的Povarov反应，以进入四氢喹啉中间体，在氧化芳构化步骤后产生相应的喹啉核。1合成技术的发展导致降低了复杂性并消除了色谱纯化。通过以高收率生产32公斤1的纯度高的产品，证明了这些改进。

更新日期：2019-11-27

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