Concise Xanthine Synthesis through a Double‐Amidination Reaction of a 6‐Chlorouracil with Amidines using Base‐Metal Catalysis

A new and concise route towards xanthines through a double‐amidination reaction is described; consecutive intermolecular C−Cl and intramolecular oxidative C−H amidination. N ‐uracil amidines are obtained through S N AE on a 6‐chlorouracil with amidines. Direct Cu‐catalyzed oxidative C−H amidination on these N ‐uracil amidines yields polysubstituted xanthines. Sustainable oxidants, t Bu 2 O 2 or O 2 , can be used in this oxidase‐type reaction. The protocol allows for the introduction of N 1, N 3, N 7, and C 8 substituents during the xanthine‐scaffold construction, thus avoiding post‐functionalization steps. Both 6‐chlorouracils and amidines are readily available commercially or through synthesis.