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

Autor(es)

de Toledo, Ian ^[1] ; Grigolo, Thiago ^[1] ; Bennett, James M. ^[2] ; Elkins, Jonathan M. ^{[2, 3]} ; Pilli, Ronaldo A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Chem, Dept Organ Chem, UNICAMP, BR-13083970 Campinas, SP - Brazil

^[2] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium, Old Rd Campus Res Bldg, Roosevelt Dr, Oxford OX3 7DQ - England

^[3] Univ Estadual Campinas, Dept Genet & Evolucao, Inst Biol, Struct Genom Consortium, BR-13083886 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Organic Chemistry; v. 84, n. 21, p. 14187-14201, NOV 1 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/13104-5 - Planejamento e síntese de inibidores baseado em alvo biológico: o caso das quinases negligenciadas
• Beneficiário: Ronaldo Aloise Pilli
• Linha de fomento: Auxílio à Pesquisa - Regular