Investigation into a Tetrahydroquinazoline Scaffold

Abstract

AbstractA new 5,6,7,8‐tetrahydroquinazoline (i. e. 1,3‐diazanaphthalene) scaffold with four points of diversification RA−RD was prepared. The sequence started from nitroalkanes RCCH2NO2 (with RC = Me, Bu), ethyl acrylate and amidines RAC(NH)NH2 (with RA = 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 RB were introduced by nucleophilic substitution with alkyl amines RBNH2 (10 examples) or aryl thiols RBSH (two examples). Finally, the nitro group in the 6‐position was reduced and the primary amino function amidated with various carboxylic acids RDCO2H. Along this seven‐step sequence, eight examples of the fully decorated scaffold were prepared.