Concise Synthesis of Versatile Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones

The synthesis of a series of imidazo[S,1-f][1,2,4]triazin-4(3H)-ones was developed from starting imidazoles in three linear steps. The synthetic sequence began with an electrophilic amination and thus a rigorous campaign to identify safe reagent and reaction conditions was performed to ensure safety for preparation of these versatile intermediates on large scales. Functionalizations at the key positions on these substrates were exemplified to demonstrate ability to perform late-stage diversification for efficient SAR discovery.