A General and Efficient Route to 6-Methyl-pyrazin-2-yl-amines : Alkylation of 2,6-Dichloropyrazine via Malonate Derivatives

We have developed a convenient two-stage process for the synthesis of 6-methylpyrazine-2-yl-amines from commercially available materials. The procedure involves the synthesis of (6-chloro-pyrazin-2-yl)-acetic acid via arylation of diethyl malonate and in situ hydrolysis/decarboxylation. A second decarboxylation takes place under the subsequent amination conditions allowing simple and efficient access to the intended pyrazines.