Three-Step Synthesis of 3-Aminoindole-2-carboxylate-Conjugated 2-Amino-6-chloropyrimidines and Their Anticancer Activity

Abstract The synthesis of novel indolo-pyrimidine derivatives is of considerable interest due to the combined pharmacological benefits of indole and pyrimidine cores, particularly for anticancer applications. In this study, we report an efficient three-step synthesis of a novel series of 3-amino-1-(2-amino-6-chloropyrimidin-4-yl)-1H-indole-2-carboxylate derivatives, employing specific bases and solvents, in high yields. The synthetic route proceeds through key intermediates: 2-aminopyrimidine-benzonitriles and 2-aminopyrimidine-glycinates, culminating in the formation of 2-aminopyrimidine-indole hybrids. Biological evaluation of the products against three human cancer cell lines and one normal cell line revealed moderate anticancer activity and minimal toxicity, highlighting their potential as promising leads for further anticancer drug development.