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Buchwald-Hartwig amination of the chloro substituted benzobicyclo[3.2.1]octadiene skeleton

Aryl amines are very important compounds in organic synthesis because of their numerous roles in chemistry, pharmaceuticals, materials sciences and polymers [1]. Transition metal catalyzed C-N bond formation has become a prevailing and reliable method for the synthesis of a variety of aromatic amines under mild and convenient conditions [1-3]. Promising test results on cholinesterase inhibitory activity of previously described benzobicyclo[3.2.1]octadienes [4] prompted us to continue with the further functionalization of this basic skeleton. Novel benzobicyclo[3.2.1]octadiene benzylamines were prepared for the first time by Buchwald-Hartwig amination from the photoproduct obtained by highly efficient continuous flow-photochemistry setup [5]. The novel amino substituted benzobicyclo[3.2.1]octadienes are especially interesting because of their methano-bridged junction of the three aromatic units at defined geometries as this gives them potential as molecular clips with very promising ADME properties due to the amino functional group [6]. Also, new amino derivatives should have better ADME properties, especially logP values which determine that those compounds could possess good blood-brain barrier penetration capability and exhibit CNS activity. [1] P. Ruiz-Castillo, S. L. Buchwald, Chem. Rev. 116 (2016) 12564-12649. [2] a) Y. Q. Fang, R. Karisch, M. Lautens, J. Org. Chem. 72 (2007) 1341-1346. [3] M. Nirmala, J. Organometallic Chem. 831 (2017) 1-10. [4] Results in the process of publishing [5] A. Ratković, Ž. Marinić, I. Škorić, J. Mol. Struct. 1168 (2018) 165-174. [6] A. Ratković, V. Kelava, Ž. Marinić, I. Škorić, J. Mol. Struct. 1179 (2019) 597-607.

Buchwald-Hartwig amination, benzobicyclo[3.2.1]octadiene, substitution of chloro-derivative, ADME properties, cholinesterase inhibitory activity

Financial support for young scientists or advanced students by International Union of Pure and Applied Chemistry (IUPAC)