Unusual nucleophilic addition of Grignard reagents in the synthesis of 4-amino-pyrimidines

Ryan A. J. Tinson, David L. Hughes, Leanne Ward, G. Richard Stephenson

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Pyrimidines have always received considerable attention because of their importance in synthesis and elucidation of biochemical roles, in particular that of vitamin B1. Herein, we describe a reaction pathway in a Grignard reagent-based synthesis of substituted pyrimidines. A general synthesis of α-keto-2-methyl-4-amino pyrimidines and their C6-substituted analogues from 4-amino-5-cyano-2-methylpyrimidine is reported. The presence of the nitrile substituent in the starting material also results in an unusual reaction pathway leading to C6-substituted 1,2-dihydropyrimidines. Grignard reagents that give normal pyrimidine products under standard reaction conditions can be 14 switched to give dihydropyrimidines by holding the reaction at 0 °C before quenching.
Original languageEnglish
Pages (from-to)8937-8944
Number of pages8
JournalACS Omega
Issue number8
Early online date10 Aug 2018
Publication statusPublished - 31 Aug 2018


  • Pyrimidines
  • Regioselectivity

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