Direct Metallation of Heteroaromatic Esters and Nitriles Using a Mixed Lithium-Cadmium Base. Subsequent Conversion to Dipyridopyrimidinones.
GheniaBentabed-Ababsa, SidatyCheikh Sid Ely, St_ephanieHesse,
EkhlassNassar,*,z FlorisChevallier, Tan Tai Nguyen, Aı¨chaDerdour, and Florence Mongin* J.Org. Chem. 2010,75, 839–847, American Chemical Society (USA)
Abstract:
All pyridine nitriles and esters were metalated at the position next to the directing group using 0.5 equiv of (TMP)3CdLi in tetrahydrofuran at room temperature for 2 h. Subsequent trapping with iodine afforded the iodo derivatives in yields ranging from 30 to 65%. The ethyl iodopyridinecarboxylates thus obtained were then involved in a one-pot palladium-catalyzed cross-coupling reaction/ cyclization using 2-aminopyridine to afford new polycyclic compounds containing a pyridopyrimidinone moiety, which were evaluated for their bactericidal and fungicidal activity. Some of the newly synthesized compounds were tested for their antitumor activity.
