Synthesis of a 2,6,8,9-Tetrasubstituted Purine Library

Significance

ArgoGel-MB-CHO resin 1 was treated with amines 2 in the presence of Na(OAc)₃BH to give the resin-bound amines 3. Reaction of 3 with 4,6-dichloro-2-(methylthio)-5-nitropyrimidine 4, followed by treatment of the resulting 5 with amines 6 afforded 7. After the oxone-mediated oxidation of the methylthio group to the sulfone 8, the substitution with amines 9 was carried out at room temperature to give 10. Reduction of the nitro group by CrCl₂ gave 11, which underwent cyclization with orthoesters 12 to give the resin-bound purines 13. Cleavage of the polymer support provided 2,6,8,9-tetrasubstituted purines 14 in 18-98% purity.