Symmetric 4,6-Dialkyl/arylamino-5-nitropyrimidines: Theoretical Explanation of Why Aminolysis of Alkoxy Groups Is Favoured over Chlorine Aminolysis in Nitro-Activated Pyrimidines.

Abstract

A new synthetic route to obtain symmetric disubstituted alkyl/arylaminopyrimidines under mild conditions is presented, which can be used to generate new purine libraries for drug discovery. We investigated the unexpected reaction of 6-alkoxy-4-chloro-5-nitropyrimidines with primary amines, which produced disubstituted dialkyl/arylamine pyrimidines instead of the expected 6-alkoxy-4-alkylamine-5-nitropyrimidines. To clarify this reaction, a computational study of the reaction mechanism was carried out and it was found that the Meisenheimer complex may play a key role in this reaction.