Synthesis of 2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one derivatives using trifluoroacetimidoyl chlorides

•Synthesis of 2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-ones was developed.•Trifluoroacetimidoyl chlorides were used for the preparation of novel CF3-heterocycles.•2-Chloro-3-acetyl-quinolines reacted with imidoyl chlorides using NaH/THF.•The reaction is thought to occur through an enaminone intermediate not isolated.•CF3 substituted benzonaphthyridin-4(1H)-ones were obtained in moderate to good yields.

A simple protocol is described for the synthesis of 2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one derivatives. The reaction between diverse 2-chloro-3-acetyl-quinolines with trifluoroacetimidoyl chlorides using sodium hydride in THF at room temperature gives directly the title compounds without isolation of intermediates. Starting 2-chloro-3-acetyl-quinolines were easily prepared in two steps from readily available 2-chloro-3-formyl-quinolines.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide