Regioselective synthesis of multiply halogenated azaxanthones

Four multiply halogenated azaxanthones 3, 4b, 5, and 6 were synthesized as novel core building blocks of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors. Each of these heterocycles requires a specific synthetic strategy to control not only the aza-positions, but also the regiochemistry of the fully differentiated and highly reactive halogen substituents.