Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1841-1852 |
Number of pages | 12 |
Journal | Organic Process Research and Development |
Volume | 25 |
Issue number | 8 |
DOIs | |
State | Published - Aug 20 2021 |
Keywords
- Conrad-Limpach reaction
- ELQ-300
- ELQ-316
- Ullmann reaction
- antimalarial
- antiparasitic
- practical synthesis
- process development
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry