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Synthesis 2019; 51(18): 3491-3498
DOI: 10.1055/s-0039-1689916
paper
© Georg Thieme Verlag Stuttgart · New York

A Facile Access to Novel (5+5) Annellated Heterocycles: Synthesis of a Furopyrrole, an Imidazoimidazole and a Pyrroloimidazole

Pavol Zlatoidský∗
a   Medicinal Chemistry, Respiratory, Inflammation And Autoimmunity, iMED Biotech. Unit, AstraZeneca, 43183 Gothenburg, Sweden
,
Elisa Martinelli
a   Medicinal Chemistry, Respiratory, Inflammation And Autoimmunity, iMED Biotech. Unit, AstraZeneca, 43183 Gothenburg, Sweden
,
Emil Svensson
b   Department of Chemistry and Molecular Biology, University of Gothenburg, 41296 Gothenburg, Sweden
,
Alexis Pruvost
c   Faculte dé Pharmacie, Université de Lille, 59800 Lille, France   Email: Pavol.Zlatoidsky@astrazeneca.com
› Author Affiliations
Further Information

Publication History

Received: 11 March 2019

Accepted after revision: 14 May 2019

Publication Date:
25 June 2019 (online)

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Abstract

We describe the synthesis of an ethyl 3-aryl-6H-furo[2,3-b]pyrrole-5-carboxylate 2, a 5-aryl-1H-imidazo[1,2-a]imidazole 3, and an ethyl-1-aryl-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylate 4 as new hinge-binding motifs for PI3K kinase inhibitors. A key reaction for the formation of 2 and 4 is the Hemmetsberger–Knittel cyclization of acryloazides. The core of 3 is accessible through reaction of an α-haloketone with 2-aminoimidazole.

Key words

Hemmetsberger–Knittel cyclization - PI3K kinase inhibitors - adeninomimetics - (5+5) annellated heterocycles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1689916.
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