A Facile Synthesis of 6-Substituted 7-Arylthieno[2,3-b]pyrazines from 2-Chloropyrazine

Abstract

A series of 6,7-disubstituted thieno[2,3-b]pyrazines were prepared by two-or three-pot reaction sequences starting from commercially available 2-chloropyrazine.The reaction of 2-chloro-3-lithiopyrazine with N,Ndimethylbenzamides gave directly aryl(3-chloropyrazin-2-yl)methanones, which were treated successively with sodium sulfide, BrCH 2 EWG (EWG = CN, CO 2 t-Bu, COAr), and sodium hydride to give the corresponding 6-substituted 7-arylthieno[2,3-b]pyrazines.Similarly, 6-substituted 7-heterarylthieno[2,3-b]pyrazines were prepared from (3-chloropyrazin-2-yl)heterarylmethanones, derived by the reaction of 2-chloro-3-lithiopyrazine with heteraromatic aldehydes followed by the PCC oxidation.