New Scalable Synthetic Routes to ELQ-300, ELQ-316, and Other Antiparasitic Quinolones

26 Sep 2021

Sovitj Pou, Rozalia A. Dodean, Lisa Frueh, Katherine M. Liebman, Rory T. Gallagher, Haihong Jin, Robert T. Jacobs, Aaron Nilsen, David R. Stuart, J. Stone Doggett, Michael K. Riscoe, Rolf W. Winter

American Chemical Society

Doi: 10.1021/acs.oprd.1c00099

Photo: Gerasimov_iStock

The endochin-like quinolone (ELQ) compound class may yield effective, safe treatments for a range of important human and animal afflictions. However, to access the public health potential of this compound series, a synthetic route needed to be devised, which would lower costs and be amenable to large-scale production. In the new synthetic route described here, a substituted β-keto ester, formed by an Ullmann reaction and subsequent acylation, is reacted with an aniline via a Conrad–Limpach reaction to produce 3-substituted 4(1H)-quinolones such as ELQ-300 and ELQ-316. This synthetic route, the first described to be truly amenable to industrial-scale production, is relatively short (five reaction steps), does not require palladium, chromatographic separation, or protecting group chemistry, and may be performed without high vacuum distillation.

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