Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 3

Experiments to effect Sonogashira (Ph3P)2Cl2Pd–CuI-based coupling of 3-methylpentyn-3-ol at C-2 of a 2-iodo-6-thiopurine derivative, bound via the sulfur atom to a Merrifield resin failed. In contrast, the analogous reaction with Pd(dppe)Cl2 and trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium catalysts were successful (20–25%), indicating that (Ph3P)2Pd(0) loses its ligands irreversibly on contact with the resin bound purine. The coupling yield was improved considerably (58%) using a Merrifield resin in which a valeric acid linker is interposed between the purine and the resin.