Synthesis of diverse nitrogen-enriched heterocyclic scaffolds using a suite of tunable one-pot multicomponent reactions.
Five elegant and switchable three-component reactions which enable access to a new series of nitrogen-containing heterocycles are reported. A novel one-step addition of an isocyanide to a hydrazine derived Schiff base affords unique six-membered pyridotriazine scaffolds (A and E). With slight modification of reaction conditions and replacement of the nucleophilic isocyanide moiety with different electrophiles (i.e., isocyanates, isothiocyanates, cyclic anhydrides, and acyl chlorides) five-membered triazolopyridine scaffolds (B, D, F, G) are generated in a single step. Furthermore, the use of phenyl hydrazine enables access to dihydroindazole-carboxamides, devoid of a bridge-head nitrogen (C). All protocols are robust and tolerate a diverse collection of reactants, and as such, it is expected that the new scaffolds and associated chemistry will garner high interest from medicinal chemists involved in either file enhancement or specific target-related drug discovery campaigns.
Department of Pharmacology and Toxicology, College of Pharmacy BIO5 Oro Valley, The University of Arizona , 1580 East Hanley Boulevard, Oro Valley, Arizona 85737, United States.
Guillermo
G
Martinez-Ariza
Muhammad
M
Ayaz
Federico
F
Medda
Christopher
C
Hulme
D055808:Drug Discovery; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry*; D017953:Isocyanates / Q000737:chemistry*; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D013237:Stereoisomerism
D006571:Heterocyclic Compounds; D006834:Hydrazines; D017953:Isocyanates; D009584:Nitrogen