Efficient synthesis of 1,3,7-substituted xanthines by a safety-catch protection strategy

An efficient synthesis of selectively N-substituted xanthine derivatives is described. Cyclocondensation of a suitably protected aminoimidazole with methyl-2-phenylthioethyl carbamate, followed by oxidation of sulfur to the sulfone, provides access to an orthogonally 1,7-protected xanthine, which may then be regioselectively alkylated and deprotected under mild conditions.