REGIOSPECIFIC ELECTROPHILIC SUBSTITUTION OF AMINOQUINAZOLINONES - DIRECTED LITHIATION OF 3-(PIVALOYLAMINO)-2-METHYLQUINAZOLIN-4(3H)-ONES AND 3-(ACETYLAMINO)-2-METHYLQUINAZOLIN-4(3H)-ONES

The 2-methyl group in 3-(pivaloylamino)- and in 3-(acetylamino)-2-methylquinazolin-4(3H)-ones has been lithiated with butyllithium. The lithium reagents thus obtained react with a variety of electrophiles (benzophenone, methyl iodide, D2O, cyclohexanone, acetophenone, phenyl isocyanate) to give the corresponding substituted derivatives in very good yields. The amide group has been cleaved in good yield under basic conditions for one model case to provide convenient access to 3-amino-2-ethylquinazolin-4(3H)-one. The NMR spectra of the 2-substituted 3-acylaminoquinazolin-4(3H)-ones show diastereotopism of the CH2 group at position 2.