Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 1

To validate a proposed solid support synthesis strategy for the construction of 2,6,9-trisubstituted purine based CDK inhibitors, the N-9 THP protected 6-benzylthio-2-iodopurine 11 was reacted with piperidine-2-methanol to give 12. Alternatively, intermediate 11 was converted to the C-2 acetylenyl substituted purine 16 in five steps, involving N-9 alkylation (Mitsunobu reaction), a Pd(0)–CuI-catalyzed acetylene coupling, selective activation of the 6-sulfur substituent and its displacement by ArCH2NH2.