Fused Systems Based on 2-Aminopyrimidines: Synthesis Combining Deprotolithiation-in situ Zincation with N-Arylation Reactions and Biological Properties.

Various aromatic ketones were first functionalized next to the carbonyl function by deprotolithiation in the presence of a zinc salt followed by iodolysis. The outcome of the reactions was analyzed, and in particular their regioselectivity in the light of the calculated pKa values. Various halogenated ketones were next involved in copper-catalyzed twofold C-N bond formation to obtain fused systems based on 2-aminopyrimidines. Besides a potential antibacterial effect, 2-aminobenzothiopyrano[4,3,2-de]quinazoline was shown to inhibit PIM1 (IC50: 0.61 μM) and CDK2/cyclin A (IC50: 2.0 μM) kinases. [ABSTRACT FROM AUTHOR]