Chemical Transformation of Pyrazine Derivatives

Abstract

Pyrazine is a group of N-containing heterocycle compounds found in both nature and synthetic drugs. In fact, the existence of the pyrazine ring as a basic framework in many drug compounds indicates that these compounds are important in drug development/design. Pyrazine as medicinal compounds, especially as anticancer, contain amine or amide groups, while some functional groups, like bromo, methyl, methoxy, nitro, amino, and methylamino have antimigration and antiproliferative activities. Based on these considerations, various chemical transformations, consisting of nitration, acetylation, esterification, bromination, and amidation have been carried out on commercially available pyrazine based starting materials containing amine or amide groups. Those chemical transformation resulting in seven pyrazine derivatives that have the potential to be applied as anticancer, namely 3-hydroxy-6-nitropyrazine-2-carboxamide (1), 3-(acetylcarbamoyl)-5-bromopyrazine-2-yl acetate (2), methyl 3-aminopyrazine-2-carboxylate (3), 3-amino-N-phenylpyrazine-2-carboxamide (4), 3-amino-N-methylpyrazine-2-carboxamide (5), methyl 3-amino-6-bromopyrazine-2-carboxylate (6), and 3,5-dibromopyrazine-2-amine (7). The molecular structures of these compounds were elucidated based on the ¹H NMR, ¹³C NMR and Mass Spectral data.