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Modular Synthesis of Di- and Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors.

ABSTRACT: A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH-imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted NH-imidazoles (23%-69%, three steps). This approach was also employed in the synthesis of known inhibitor GSK3037619A.

SUBMITTER: de Toledo I

PROVIDER: S-EPMC6829625 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Modular Synthesis of Di- and Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors.

de Toledo Ian I Grigolo Thiago A TA Bennett James M JM Elkins Jonathan M JM Pilli Ronaldo A RA

The Journal of organic chemistry 20190930 21

A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH-imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted ...[more]

PMID: 31460764

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