Direct C-H arylation of purine on solid phase and its use for chemical libraries synthesis
Barbora Vanková1, Viktor Krchnák, Miroslav Soural
1Department of Organic Chemistry, Faculty of Science, Institute of Molecular and Translational Medicine, University of Palacký, Olomouc, Czech Republic.
Abstract:
C(8)-H direct arylation of purine derivatives immobilized on Wang resin is described. The purine skeleton was immobilized via C(6)-regioselective substitution of 2,6-dichloropurine with polymer-supported amines. After N(9)-alkylation with two different alkyl iodides and C(2) substitution with two selected amines, reaction conditions for C(8)-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.
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