Exploring the Synthetic Reactivity of Brominated 2‐Aminopyrazines

The 2‐amino‐3,5‐dibromopyrazine ( 1 ) ring has been prepared from 2‐aminopyrazine using NBS in quantitative yields. Several reactions have been carried out to replace bromine with aromatic rings, alkynes, amines, or phenols. In all cases, the bromine atom at position 3 of the substituted pyrazine has been substituted regioselectively. The high regioselectivity indicates that the carbon at position 3 of 2‐amino‐3,5‐dibromopyrazine has a more electrophilic character than that at position 5. Alkynylation using Sonogashira reaction conditions allows mono‐ and di‐substitution in high yields. Monoarylation was obtained under Suzuki–Miyaura reaction conditions in acceptable yields. It has also been found that the selective amination of position 3 of piperazine 1 can be obtained under cross‐coupling conditions and also through an aromatic nucleophilic substitution (S N Ar).