Fused Systems Based on 2‐Aminopyrimidines: Synthesis Combining Deprotolithiation‐in situ Zincation with <i>N</i>‐Arylation Reactions and Biological Properties

Abstract

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 p K a 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 (IC 50 : 0.61 µ m ) and CDK2/cyclin A (IC 50 : 2.0 µ m ) kinases.