Direct Mechanochemical Amination of [1,2,4]Triazolo[1,5-a]pyrimidin-7-ones via C–O Bond Activation

A novel, solvent-free method for the direct amination of [1,2,4]triazolo[1,5-a]pyrimidin-7-ones has been developed via mechanochemical ball milling. Utilizing a Ph3P–I2 system as a C–O bond activator, this one-pot protocol efficiently overcomes the poor solubility of these substrates in conventional solvents. Optimization revealed that chloro(trimethyl)silane (TMSCl) is essential for achieving high yields by sequestering trace water. The reaction scope is broad, providing access to 32 derivatives in 54–87% yield from both aromatic and aliphatic amines, with good tolerance for functional groups such as CF3, Br, Cl, and F.