Synthesis of pyrimidine linked heterocyclic scaffolds by intramolecular cyclization and study of biological potential

Abstract

Synthesis of some interesting pyrimidine linked heterocyclic scaffolds by intramolecular cyclization has been worked out. Initially compound (4,6-dimethyl-pyrimidin-2-yl-amino)-acetic acid hydrazide has been prepared by reacting 2-amino-4,6-dimethyl pyrimidine with ethyl chloroacetate, followed by condensation with hydrazine hydrate. It has then been treated with N-aryl/alkyl isothiocyanates, followed by intramolecular cyclization using alkaline ethanolic solution of I₂ with KI, o-phosphoric acid and aqueous KOH to afford respective heterocyclic compounds with differently substituted pharmacophores viz. (5-aryl/alkyl-amino-[1,3,4]-oxadiazol-2-yl-methyl)-(4,6-dimethyl-pyrimidin-2-yl)-amines, (5-aryl/alkyl-amino-[1,3,4]-thiadiazol-2-yl-methyl)-(4,6-dimethyl-pyrimidin-2-yl)-amines and (4-aryl/alkyl-5-mercapto-[1,2,4]-triazol-3-yl-methyl)-(4,6-dimethyl-pyrimidin-2-yl)-amines. Developments during the synthesis have been monitored by TLC. Constitution of synthesized compounds have been delineated in accordance with equivalent weight, elemental assay,chemical transformation and IR, ¹H NMR and mass spectral investigations. Title compounds have been tested for their biological potential.