Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 2

Purine bound resins 1a–c were obtained by the reaction of 6-thiopurines 2 or 6-chloropurines 3–5 with Merrifield-Cl or -SH resins (DMF, 70°C, base). S-Oxidation of resins 1c and reaction of the desired sulfone with p-methoxybenzylamine to give 6, proved effective for release of the purine from the resin and simultaneous C-6 substitution. Reaction of resin 1c with pyrrolidine and pyrrolidine-2-methanol prior to S-oxidation led to the C-2 amine substituted resin bound purines 8 and 9. Activation of sulfur in these intermediates, followed by reaction with Ar–CH2–NH2 gave the 2,6,9-trisubstituted purines 10–14 in 42–60% yields.