cs400926z_si_001.pdf (240.84 kB)
Synthesis of Pyridopyrimidines by Palladium-Catalyzed Isocyanide Insertion
journal contribution
posted on 2014-01-03, 00:00 authored by Verónica Estévez, Gitte Van Baelen, Babette H. Lentferink, Tjøstil Vlaar, Elwin Janssen, Bert U. W. Maes, Romano V. A. Orru, Eelco RuijterA new
synthetic approach to 4-aminopyrido[2,3-d]pyrimidines
and 4-aminopyrido[3,2-d]pyrimidines
based on palladium-catalyzed reaction of isocyanides with readily
available N-(bromopyridyl)amidines is reported. The
target heterocycles were obtained in generally good to excellent yield.
For the two regioisomeric pyrimidopyrimidines, we compared our approach
involving oxidative addition with the analogous C–H activation
protocol because both methods have been reported for the synthesis
of 4-aminoquinazolines. We found that the C–H activation protocol
does not allow one to obtain the target pyridopyrimidines, but the
imidoylative cross-coupling protocol provided a new entry to the synthesis
of these medicinally important scaffolds.