Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

Abstract

1,2,4-Triazolo[4,3-a]pyrazines have previously been explored by the Open Source Malaria project as potent in vitro and in vivo antimalarial drug leads. With a view to generating a library of unique antimalarial 1,2,4-triazolo[4,3-a]pyrazines and exploring regiochemical preference for nucleophilic amines, we utilised the known synthetic 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (1) as a scaffold for aminations with 14 commercially available primary amines. Reacting scaffold 1 with excess primary amine at room temperature for 16 h generated the desired amine analogues in respectable yields (18–87%) and high purity (≥95%) following chromatography workup. The structures of the 1..