Quinazolines and Pyrimidines by Electrophilic Activation of Amides

Significance

A mild preparation of quinazoline and pyrimidine derivatives via a one-pot reaction of nitriles with amides under triflic anhydride activation is reported. The reaction requires 2-chloropyridine (A. G. Myers, N. J. Tom, M. E. Fraley, S. B. Cohen, D. J. Madar J. Am. Chem. Soc. 1997, 119, 6072-6094) which leads to the formation of a 2-chloropyridinium intermediate that may be detected by NMR and React-IR spectroscopy as previously shown by Charette et al. (Org. Lett. 2005, 7, 5401-5404). Reasonably broad substrate scope was surveyed which showed a preference for electron-rich N-aryl, heteroaryl, and vinyl amides. Aromatic and aliphatic nitriles participate effectively in the reaction. Even substrates bearing epimerizable stereogenic centers undergo reaction with no loss in optical activity.