2-(benzylsulfanyl)-6-chloro-9-isopropylpurine, a valuable intermediate in the synthesis of diaminopurine cyclin dependent kinase inhibitors

D Taddei, A M Z Slawin, J D Woollins

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9 Citations (Scopus)

Abstract

The synthetic potential of a novel precursor of 2,6-diaminopurine CDK inhibitors, 2-(benzylsulfanyl)-6-chloro-9-isopropylpurine, is described. The Traube purine synthesis was chosen to prepare the required 2-(benzylsulfanyl)hypoxanthine intermediate. Attempts to prepare its purin-6-yl methanesulfonic ester analogue failed. Conversion to the 6-chloropurine derivative enabled the introduction of arylamines in the presence of catalytic amounts of acid. Further chemical variety was introduced on the purine through a regioselective Mitsunobu N-9 alkylation. Oxidative cleavage of the 2(benzylsulfanyl) leaving group with an aliphatic amine was implemented as previously reported. Purvalanol A, a potent CDK inhibitor, was synthesised using this methodology. The template and intermediates were fully characterised by modern spectroscopic techniques and single-crystal X-ray diffraction. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).

Original languageEnglish
Pages (from-to)939-947
Number of pages9
JournalEuropean Journal of Organic Chemistry
DOIs
Publication statusPublished - 25 Feb 2005

Keywords

  • antitumor agents
  • enzymes
  • inhibitors
  • nitrogen heterocycles
  • template synthesis
  • SOLID-PHASE SYNTHESIS
  • IN-VITRO EVALUATION
  • 2,6,9-TRISUBSTITUTED PURINES
  • CELL-CYCLE
  • DERIVATIVES
  • DESIGN
  • POTENT

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