Green synthesis of structural analogs of favipiravir†

A series of 3-hydroxy-5-arylpyrazine-2-carboxamides, structural analogs of favipiravir, have been successfully synthesized using a green and sustainable method through a one-pot condensation reaction of arylglyoxals 1a–i and 2-aminopropanediamide 2 in an alkaline solution under heating conditions. The reaction is temperature-sensitive; when conducted at 80 °C, 5-aryl substituted pyrazine derivatives were predominantly obtained. In reactions with arylglyoxals 1a, 1d, 1h, and 1i, temperatures exceeding 80 °C produced a mixture of two regioisomeric pyrazine derivatives with significant efficiency. This method is highly desirable due to its short reaction time, simple purification of products, and the use of water as an eco-friendly solvent.