1-Alkyl- and (±)-1,2-dialkyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones by a tandem Michael-SNAr annulation reaction

Richard A Bunce; Scott T Squires; Baskar Nammalwar

doi:10.1021/jo3018632

1-Alkyl- and (±)-1,2-dialkyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones by a tandem Michael-SNAr annulation reaction

J Org Chem. 2013 Mar 1;78(5):2144-8. doi: 10.1021/jo3018632. Epub 2012 Nov 12.

Authors

Richard A Bunce¹, Scott T Squires, Baskar Nammalwar

Affiliation

¹ Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078-3071, United States. rab@okstate.edu

PMID: 23113469
DOI: 10.1021/jo3018632

Abstract

A tandem Michael-S(N)Ar annulation reaction has been developed for the synthesis of 1-alkyl and (±)-1,2-dialkyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones. Treatment of 1-(2-chloropyridin-3-yl)prop-2-en-1-one (R = H) or (E or Z)-1-(2-chloropyridin-3-yl)but-2-en-1-one (R = CH3) with R'NH2 in DMF at 50 °C for 24 h provides 2,3-dihydro-1,8-naphthyridin-4(1H)-ones in 65-85% yields. Mechanistic studies suggest that the reaction sequence is initiated by Michael addition to the side chain enone.