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Fused Systems Based on 2‐Aminopyrimidines: Synthesis Combining Deprotolithiation‐in situ Zincation with N ‐Arylation Reactions and Biological Properties
Author(s) -
Hedidi Madani,
Maillard Julien,
Erb William,
Lassagne Frédéric,
Halauko Yury S.,
Ivashkevich Oleg A.,
Matulis Vadim E.,
Roisnel Thierry,
Dorcet Vincent,
Hamzé Monzer,
Fajloun Ziad,
Baratte Blandine,
Ruchaud Sandrine,
Bach Stéphane,
BentabedAbabsa Ghenia,
Mongin Florence
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201701004
Subject(s) - regioselectivity , chemistry , zinc , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , catalysis
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.