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.