Fused Systems Based on 2‐Aminopyrimidines: Synthesis Combining Deprotolithiation‐in situ Zincation with N‐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 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.

From Quinoxaline, Pyrido[2,3-b]pyrazine and Pyrido[3,4-b]pyrazine to Pyrazino-Fused Carbazoles and Carbolines

“…It is possible to replace Zn(TMP) 2 by ZnCl 2 provided that there is no contact between LiTMP and ZnCl 2 in the absence of the aromatic compound [23,24]. Thus, Method B is limited to activated substrates for which deprotonation is favored over reaction between LiTMP and ZnCl 2 .…”

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

“…Hedidi et al reported the copper catalyzed synthesis of pyrido[2,3- e ]pyrimidines 297 (Hedidi et al, 2017 ). The attempts to obtain the target compounds via simple heating of the reagents 5a, 31, 101a , and 296 with Cs 2 CO 3 in DMF, as it had been reported in Niu et al ( 2014 ), were unsuccessful while application of the procedure reported by Gao et al ( 2014 ) allowed to fix their traces.…”

Trans‐Metal‐Trapping: Concealed Crossover Complexes En Route to Transmetallation?

“…Mongin has also used salt adduct ZnCl 2 ·TMEDA as at rap in reactions of LiTMP with diarylketones, whicht hen undergo iodolysis. [33] From NMR and IR spectroscopics tudies, it was concludedt hat ZnCl 2 ·TMEDA only operates after lithiation and intercepts theg enerated aryllithium.T he transmetallation product TMPZnCl·LiClwas ruled out as the base since it is incapable of deprotonation at low temperature.…”

“…Mongin has also used salt adduct ZnCl 2 ⋅TMEDA as a trap in reactions of LiTMP with diarylketones, which then undergo iodolysis . From NMR and IR spectroscopic studies, it was concluded that ZnCl 2 ⋅TMEDA only operates after lithiation and intercepts the generated aryllithium.…”