New Scalable Synthetic Routes to ELQ-300, ELQ-316, and Other Antiparasitic Quinolones
Organic Process Research & Development
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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Pou, S., Dodean, R. A., Frueh, L., Liebman, K. M., Gallagher, R. T., Jin, H., Jacobs, R. T., Nilsen, A., Stuart, D. R., Doggett, J. S., Riscoe, M. K., & Winter, R. W. (2021). New Scalable Synthetic Routes to ELQ-300 , ELQ-316 , and Other Antiparasitic Quinolones. Organic Process Research & Development, 25(8), 1841–1852. https://doi.org/10.1021/acs.oprd.1c00099