A facile, efficient and mild synthesis of 2, 6, 9-tri-substituted purines is presented, starting from commercially available 2-amino-6-chloropurine, which employs sequential N9 then N2 Mitsunobu reactions as key steps. Importantly, our synthetic approach to N2- functionalization of the purine nucleus obviates the harsh conditions required by the traditional nucleophilic aromatic substitution of a 2-halo group with primary amines. ...