Investigation into a Tetrahydroquinazoline Scaffold

A new 5,6,7,8‐tetrahydroquinazoline (i. e. 1,3‐diazanaphthalene) scaffold with four points of diversification R^A−R^D was prepared. The sequence started from nitroalkanes R^CCH₂NO₂ (with R^C = Me, Bu), ethyl acrylate and amidines R^AC(NH)NH₂ (with R^A = Ph, 4‐pyridyl) which were converted in a conjugate addition, Dieckmann condensation and pyrimidine ring formation. After transformation of the OH group in 4‐position to a chloro leaving group, residues R^B were introduced by nucleophilic substitution with alkyl amines R^BNH₂ (10 examples) or aryl thiols R^BSH (two examples). Finally, the nitro group in the 6‐position was reduced and the primary amino function amidated with various carboxylic acids R^DCO₂H. Along this seven‐step sequence, eight examples of the fully decorated scaffold were prepared.