Quinazoline ring systems, functionalizing

Amidines 14 are cyclized to quinazolines 15 in lithium alkylamide or dialkylamide mediated reactions in which the construction of the quinazoline ring system and introduction of the amino substituent occur in the same reaction. Mechanistically, each fluorine of the trifluo-romethyl substituent of the amidine is displaced by a series of internal nucleophilic processes and the resulting quinazoline contains the amino function of the lithium reagent incorporated at the C4 position. The cyclization method is suitable for the synthesis of sterically congested quinazolin-4-amines and in syntheses of derivatives for which the corresponding chloroquinaz-olines are not readily available. ... 

The synthesis of several commercially available and biologically significant quinazolines and quinazolinones are illustrated below. In most cases, the quinazoline or quinazolinone ring system is constructed from acyclic precursors and then functionalized accordingly. 

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