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Micellar Buchwald-Hartwig coupling of aryl and heteroarylamines for the synthesis of DNA-encoded libraries

Lookup NU author(s): Professor Mike Waring

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Chemical Society, 2021.

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Abstract

DNA-encoded libraries are a very efficient means of identifying ligands for protein targets in high throughput. To fully maximise their use, it is essential to be able to carry out efficient reactions on DNA-conjugated substrates. Arylamines are privileged motifs in drug-like molecules and methods for their incorporation into DNA-encoded libraries is highly desirable. One of the preferred methods for their preparation, the Buchwald-Hartwig coupling, does not perform well on-DNA conjugates using current approaches. We report the application of our recently developed micellar technology for on-DNA chemistry to the Buchwald-Hartwig reaction. Optimisation of conditions led to a robust, high yielding method for the synthesis of DNA-conjugated aryl and heteroarylamines, which is broad in substrate scope for both the arylamine and the DNA-conjugated aryl halide and is fully compatible with DNA-encoding and decoding procedures. This method will enable the preparation of diverse, high fidelity libraries of biarylamines.

Publication metadata

Author(s): Graham JS, Hunter JH, Waring MJ

Publication type: Article

Publication status: Published

Journal: Journal of Organic Chemistry

Year: 2021

Volume: 86

Issue: 23

Pages: 17257-17264

Print publication date: 03/12/2021

Online publication date: 17/11/2021

Acceptance date: 03/11/2021

Date deposited: 03/11/2021

ISSN (print): 0022-3263

ISSN (electronic): 1520-6904

Publisher: American Chemical Society

URL: https://doi.org/10.1021/acs.joc.1c02325

DOI: 10.1021/acs.joc.1c02325

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