Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction
Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction
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DOI：
10.1021/acs.oprd.9b00421
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发表时间：
2020-05-15
影响因子：
3.4
通讯作者：
Petit，Sylvain
中科院分区：
文献类型：
--
作者：
Cerfontaine，Patrick;Driessens，Frank;Petit，Sylvain
在此，我们描述了一种新的VLA-4拮抗剂1作为多发性硬化症的潜在治疗的实际合成。关键步骤是基于亚胺与烯烃的Povarov反应以获得四氢喹啉中间体，在氧化芳构化步骤后得到相应的喹啉核。1的合成的发展导致复杂性降低和消除色谱纯化。这些改进通过以高收率和优异纯度生产32 kg 1在规模上得到证实。
Herein we describe the practical synthesis of a novel VLA-4 antagonist1as 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 of1led to decreased complexity and the elimination of chromatographic purifications. These improvements were demonstrated at scale by the production of 32 kg of1in high yield with excellent purity.