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

Pavol Zlatoidský; Elisa Martinelli; Emil Svensson; Alexis Pruvost

doi:10.1055/s-0039-1689916

Synthesis, Table of Contents

Synthesis 2019; 51(18): 3491-3498
DOI: 10.1055/s-0039-1689916

paper

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

Pavol Zlatoidský∗

^aMedicinal Chemistry, Respiratory, Inflammation And Autoimmunity, iMED Biotech. Unit, AstraZeneca, 43183 Gothenburg, Sweden

,

Elisa Martinelli

^aMedicinal Chemistry, Respiratory, Inflammation And Autoimmunity, iMED Biotech. Unit, AstraZeneca, 43183 Gothenburg, Sweden

,

Emil Svensson

^bDepartment of Chemistry and Molecular Biology, University of Gothenburg, 41296 Gothenburg, Sweden

,

Alexis Pruvost

^cFaculte dé Pharmacie, Université de Lille, 59800 Lille, France Email: Pavol.Zlatoidsky@astrazeneca.com

› Author Affiliations

Abstract

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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

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References

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