Utility of 4,6-dichloro-2-(methylthio)-5-nitropyrimidine.: Part 2:: Solution phase synthesis of tetrasubstituted purines

A simple synthesis of tetrasubstituted purines is disclosed based on the solution phase elaboration of 4,6-dichloro-2-methylthio-5-nitropyrimidine. One-pot sequential C4 and C6 chloride substitution by secondary and primary amines yields 4.6-diamino-2-methylthio-5-nitropyrimidines. mCPBA-mediated oxidation of the methylthio moiety to the corresponding sulfone allows facile substitution at the 2-position. CrCl2 assisted reduction of the nitro group, followed by acid catalyzed orthoester cyclization, then provides novel tetrasubstituted purines not accessible by other methods. (C) 2003 Elsevier Ltd. All rights reserved.