LITHIATION OF 2-ALKYL-3-AMINO-4(3H)-QUINAZOLINONES AND 2-ALKYL-3-(METHYLAMINO)-4(3H)-QUINAZOLINONES

3-Amino-2-methyl-4(3H)-quinazolinone has been doubly lithiated, on nit rogen and in the 2-methyl group, with n-butyllithium. The lithium reag ent thus obtained reacts with a variety of electrophiles (D2O, benzoph enone, cyclohexanone, cyclopentanone, acetophenone, benzaldehyde, tetr aisopropyl-thiuram disulfide (TITD)) to give the corresponding a-subst ituted derivatives in very good yields. Reactions of the dilithio reag ent with 2 molar equiv of methyl iodide or phenyl isocyanate give disu bstituted derivatives. Double Lithiation of the 2-ethyl and 2-propyl a nalogues have been achieved using LDA, and subsequent reactions with m ost electophiles are then similar. In the reaction of the dianion of t he 2-ethyl compound with TITD, deamination from position 3 takes place with the formation of the 2-substituted derivative. In reactions with prochiral ketones, the dianion of the 2-ethyl compound gives very hig h diastereoselectivity. Lithiation and subsequent reactions of 3-(meth ylamino) analogues take place in a similar manner, thus providing acce ss to a range of substituted 3-(methylamino)-2-alkyl-4(3H)-quinazolino nes by a general procedure. Lithiation of 3-(dimethylamino)-2-ethyl-4( 3H)-quinazolinone did not take place under similar conditions. Lithiat ion of 3-amino-2-unsubstituted-4(3H)-quinazolinone was also unsuccessf ul.