403661-82-5Relevant academic research and scientific papers
Cyclin-dependent kinase (CDK) inhibitors: Development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 3
Brun, Virginie,Legraverend, Michel,Grierson, David S.
, p. 8169 - 8171 (2001)
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.
Traceless solid-phase synthesis of 2,6,9-trisubstituted purines from resin bound 6-thiopurines
Brun, Virginie,Legraverend, Michel,Grierson, David S
, p. 7911 - 7923 (2007/10/03)
The preparation of 6-chloro-2-iodo-9-tetrahydropyranylpurine (2), was achieved in three high yield steps from 6-chloropurine. This derivative was then selectively substituted at C-6 by reaction with a benzylthiol to give 3, a versatile intermediate for the synthesis of 2,6,9-trisubstituted purines. Reaction of 3 in palladium-catalyzed cross-coupling reactions, (including Sonogashira coupling at room temperature), as well as nucleophilic substitutions with amines occurred selectively at C-2. The 6-thiobenzyl substituent was activated through oxidation to the corresponding sulfone and replaced by various benzyl or phenyl amines. This strategy was subsequently adapted to solid support, wherein 23 is connected to Merrifield resin via a 6-thiovaleric ester linker. The presence of the linker, in combination with the use of palladacycle type catalysts improved the yield of palladium(0)-catalyzed Suzuki and Sonogashira cross-coupling reactions. This strategy opens a new route to combinatorial chemistry library synthesis of trisubstituted purines on the solid support.
