Application of Pd-Catalyzed Cross-Coupling Reactions in the Synthesis of 5,5-Dimethy1-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles that Inhibit ALK5 Kinase

0468499 - ÚEB 2017 RIV US eng J - Journal Article
Tenora, L. - Galeta, J. - Řezníčková, Eva - Kryštof, Vladimír - Potáček, M.
Application of Pd-Catalyzed Cross-Coupling Reactions in the Synthesis of 5,5-Dimethy1-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles that Inhibit ALK5 Kinase.
Journal of Organic Chemistry. Roč. 81, č. 23 (2016), s. 11841-11856. ISSN 0022-3263. E-ISSN 1520-6904
R&D Projects: GA ČR(CZ) GA15-15264S
Institutional support: RVO:61389030
Keywords : c-h functionalization * pyridine n-oxides * receptor-type-i * direct arylation * tgf-beta * galunisertib ly2157299 * domain inhibitors * bond activation * growth * withasomnine
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 4.849, year: 2016

C-H activation of position 3 of a substituted pyrazole ring catalyzed by palladium(II) was straightforward and convenient for arylated or heteroarylated 5,5-dimethyl-5,6dihydro-4H-pyrrolo[1,2-b]pyrazoles. Moreover, we introduced simple protection of the nitrogen in the pyridin-2-yl directing group, which otherwise does not allow a cross-coupling reaction, by transformation to the N-oxide. Selected final products were reasonably selective ALK5 kinase inhibitors.
Permanent Link: http://hdl.handle.net/11104/0266335