Kastrati, Agonist, Kremsmair, Alexander, Sunagatullina, Alisa S., Korotenko, Vasilii, Guersov, Yusuf C., Hess, Andreas, Rout, Saroj. K., Lima, Fabio, Brocklehurst, Cara, Karaghiosoff, Konstantin, Zipse, Hendrik and Knochel, Paul (2023) Calculation-Driven Regioselective Functionalization of the Imidazo[1,2-a]pyrazine Scaffold via Zinc and Magnesium Organometallic Intermediates. Chemical Science. ISSN 2041-65202041-6539

Abstract

Straightforward calculations such as determinations of pKa values and N-basicities have allowed the development of a set of organometallic reactions for the regioselective functionalization of the underexplored imidazo[1,2 a]pyrazine. Thus, regioselective metalations of 6 chloroimidazo[1,2-a]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl∙LiCl and TMP2Zn∙2MgCl2∙2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMP2Zn∙2MgCl2∙2LiCl as base for the first metalation allowed an alternative regioselective metalation. Nucleophilic additions at position 8 as well as selective Negishi cross-couplings complete the set of methods for selectively decorating this heterocycle of the future.

Item Type:	Article
Date Deposited:	20 Oct 2023 00:45
Last Modified:	20 Oct 2023 00:45
URI:	https://oak.novartis.com/id/eprint/50711