Direct C–H Arylation of Purine on Solid Phase and Its Use for Chemical Libraries Synthesis

C8–H direct arylation of purine derivatives immobilized on Wang resin is described. The purine skeleton was immobilized via C6-regioselective substitution of 2,6-dichloropurine with polymer-supported amines. After N9-alkylation with two different alkyl iodides and C2 substitution with two selected amines, reaction conditions for C8–H arylation were developed and optimized. Various aryl bromides and aryl iodides were used for the reaction affording the target 2,6,8,9-tetrasubstituted purines in very good purity. The same reaction conditions were also applied for the synthesis of 2,6,8-trisubstituted purines, however, yields were lower. The methodology is applicable for high throughput synthesis of chemical libraries comprised of purine scaffold.