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 o r 6-chloropurines 3-5 with Merrifield-Cl or -SH resins (DMF, 70 degreesC, b ase). S-Oxidation of resins 1c and reaction of the desired sulfone with p-m ethoxybenzyl a mine to give 6, proved effective for release of the purine f rom the resin and simultaneous C-6 substitution. Reaction of resin le 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 thes e intermediates, followed by reaction with Ar CH-NH, gave the 2,6,9-trisubs tituted purines 10-14 in 42-60% yields. (C) 2001 Elsevier Science Ltd. All rights reserved.