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Synthetic studies towards isomeric pyrazolopyrimidines as potential ATP synthesis inhibitors of Mycobacterium tuberculosis. Structural correction of reported N-(6-(2-(dimethylamino)ethoxy)-5-fluoropyridin-3-yl)-2-(4-fluorophenyl)-5-(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-7-amine

Peter J. Choi, Guo‐Liang Lu, Hamish S. Sutherland, Anna C. Giddens, Scott G. Franzblau, Christopher B. Cooper, William A. Denny, Brian D. Palmer

2021Tetrahedron Letters14 citationsDOIOpen Access PDF

Abstract

During our studies into preparing analogues of pyrazolopyrimidine as ATP synthesis inhibitors of Mycobacterium tuberculosis, a regiospecific condensation reaction between ethyl 4,4,4-trifluoroacetoacetate and 3-(4-fluorophenyl)-1H-pyrazol-5-amine was observed which was dependent on the specific reaction conditions employed. This work identifies optimized reaction conditions to access either the pyrazolo[3,4-β]pyridine or the pyrazolo[1,5-α]pyrimidine scaffold. This has led to the structural confirmation of the previously reported pyrazolopyrimidine 17b which was reported as pyrazolo[1,5-α]pyrimidine structure 2 which was corrected to pyrazolo[3,4-β]-pyrimidine 19.

Topics & Concepts

ChemistryPyrimidineMycobacterium tuberculosisPyridineStereochemistryTrifluoromethylCombinatorial chemistryMedicinal chemistryTuberculosisOrganic chemistryPathologyMedicineAlkylTuberculosis Research and EpidemiologyBiochemical and Molecular ResearchSynthesis and biological activity
Synthetic studies towards isomeric pyrazolopyrimidines as potential ATP synthesis inhibitors of Mycobacterium tuberculosis. Structural correction of reported N-(6-(2-(dimethylamino)ethoxy)-5-fluoropyridin-3-yl)-2-(4-fluorophenyl)-5-(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-7-amine | Litcius