4-Amino-imidazo-, oxazolo-, and thiazoloquinolines are key structural scaffolds in the design of nucleoside base analogs for use as therapeutic agents. Current strategies for arriving at diverse substitutions at the C6–C9 positions of the thiazolo-and oxazoloquinolines, however, are limited due to difficulties in arriving at the thiazoloquinoline-5N-oxide intermediate using electron deficient aromatic systems. Here, we demonstrate a synthetic route to obtain substituted thiazoloquinolines with electron-withdrawing groups at the C7 position. The target compound, 4-amino-2-butyl-7-methoxycarbonylthiazolo[4,5-c]quinoline, is obtained in eight steps using a 7-bromo surrogate as a precursor to the successful generation of the N-oxide intermediate, and final transformation via Pd-mediated C7-acylation.
|Original language||English (US)|
|State||Published - Dec 2021|
Bibliographical noteFunding Information:
This work was in part supported by a research grant from Seagen, Inc., Bothell, WA, USA, to D.M.F. The NMR spectroscopy component of this research was supported by Grant 1S10OD021536 from the National Institute of General Medical Sciences. The contents of this publication are the sole responsibility of the authors and do not necessarily represent the official views of NIGMS.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- 1,3-dipolar cycloaddition
- Nitrogen heterocycles
- Pd-catalyzed car-bonylation