Functionalized 4-Aminoquinolines by Rearrangement of Pyrazole N-Heterocyclic Carbenes

摘要

The quinoline and pyrazole class of substances feature diverse biological activities and other interesting properties. From the viewpoint of the chemistry of pharmacologically active compounds, considerable attention is being paid to 4-aminoquinolines, especially because after decades of use Plasmodium falciparum genotypes resistant to the active antimalarial compound chloroquine have spread to almost all tropical regions of the world. As the use of alternative active compounds is similarly restricted because of adverse effects or resistance variation of the substitution of 4-aminoquino-lines still remains highly promising despite of the decoding of the genome of the pathogen in the meantime. Herein we present a useful thermal rearrangement to new substituted 4-aminoquinolines starting from pyrazolium-3-carboxylates that proceeds by an N-heterocyclic carbene (NHC) of pyrazole. Carbenes of pyrazole and its relative, indazole, have so far stood in the shadow of other NHCs. In 1997, Herrmann's group described the rhodium complex 2 of pyrazol-3-ylidene 1; there have also been reports on the catalytic activities of iridium, ruthenium,and palladium complexes of 1.