Fused Systems Based on 2‐Aminopyrimidines: Synthesis Combining Deprotolithiation‐in situ Zincation with N‐Arylation Reactions and Biological Properties. Issue 39 (20th October 2017)

• Record Type: Journal Article
• Authors: 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; Bentabed‐Ababsa, Ghenia; Mongin, Florence
• Is Part Of: European journal of organic chemistry. Issue 39(2017)
• Page Start: 5903
• Page End: 5915
• Publication Date: 2017-10-20
• Subjects: Synthetic methods -- Ketones -- Pyrimidines -- Copper -- C–N bond formation -- Biological activity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201701004
• Languages: English
• ISSNs: 1434-193X

Abstract

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 (IC50 : 0.61 µm ) and CDK2/cyclin A (IC50 : 2.0 µm ) kinases. Abstract : Aromatic ketones were functionalized by deprotolithiation in the presence of zinc salt followed by iodolysis. Reactions were analyzed relative to calculated p K a s. Copper‐catalyzed C–N bond formation with iodo derivatives gave fused systems based on 2‐aminopyrimidines. 2‐Aminobenzothiopyrano[4, 3, 2‐ de ]quinazoline has antibacterial effect, and inhibits PIM1 (IC50 0.61 µm ) and CDK2/cyclin A (IC50 2.0 µm ) kinases.