4-Amino-2-butyl-7-methoxycarbonylthiazolo[4,5-c]quinoline

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.

Automated summary

The study presents a synthetic route to obtain substituted thiazoloquinolines with electron-withdrawing groups at the C7 position, addressing limitations in current strategies for diverse substitutions at the C6-C9 positions of thiazolo- and oxazoloquinolines.