Issue 39, 2021
From the journal:

Chemical Science

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes†

Kuno Schwärzer,a   Saroj K. Rout,a   Derya Bessinger,a   Fabio Lima,b   Cara E. Brocklehurst,b   Konstantin Karaghiosoff, ORCID logo a   Thomas Bein ORCID logo a  and  Paul Knochel ORCID logo *a  

* Corresponding authors

a Department Chemie, Ludwig-Maximilians-Universität München, Munich 81377, Germany
E-mail: Paul.Knochel@cup.uni-muenchen.de

b Global Discovery Chemistry, Novartis Institutes of BioMedical Research, Basel 4057, Switzerland

Abstract

We report the selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold using a Br/Mg-exchange, as well as regioselective magnesiations and zincations with TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl), followed by trapping reactions with various electrophiles. In addition, we report a fragmentation of the pyrazole ring, giving access to push–pull dyes with a proaromatic (1,3-dihydro-2H-imidazol-2-ylidene)malononitrile core. These functionalization methods were used in the synthesis of an isostere of the indolyl drug pruvanserin. Comparative assays between the original drug and the isostere showed that a substitution of the indole ring with a 1H-imidazo[1,2-b]pyrazole results in a significantly improved solubility in aqueous media.

Graphical abstract: Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

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Article information

DOI
https://doi.org/10.1039/D1SC04155J
Article type
Edge Article
Submitted
29 Jul 2021
Accepted
28 Aug 2021
First published
30 Aug 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 12993-13000

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Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

K. Schwärzer, S. K. Rout, D. Bessinger, F. Lima, C. E. Brocklehurst, K. Karaghiosoff, T. Bein and P. Knochel, Chem. Sci., 2021, 12, 12993 DOI: 10.1039/D1SC04155J

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