6,8-Dibromo-4-chloroquinoline-3-carbaldehyde as a synthon in the development of novel 1,6,8-triaryl-1H-pyrazolo[4,3-c]quinolines

2-Amino-3,5-dibromoacetophenone undergoes Vilsmeier reaction with a phosphoryl chloride-dimethylformamide mixture to afford 6,8-dibromo-4-chloroquinoline-3-carbaldehyde. The latter was reacted with arylhydrazine hydrochlorides in ethanol in the presence of triethylamine to afford the corresponding arylhydrazone derivatives. These hydrazones were, in turn, cyclized with ethanolic KOH (5% in ethanol) to afford the corresponding 1-aryl-6,8-dibromo-1H-pyrazolo[4,3-c]quinolines. Suzuki-Miyaura cross-coupling of these 1-aryl-6,8-dibromo-1H-pyrazolo[4,3-c]quinolines with arylboronic acids afforded novel 1,6,8-triaryl-1H-pyrolo[4,3-c]quinolines.

Reagents and conditions: (i) KOH, EtOH, heat, 3 h; (ii) Ar′B(OH)2, PdCl2(PPh3)2, PCy3, K2CO3, DMF-water (3/1, v/v), heat, 3 h.