Synthesis of 2,4,8‐Trisubstituted 1,7‐Naphthyridines by the Reaction of 4‐(1‐Aryl‐2‐methoxyethenyl)‐3‐isocyanopyridines with Excess Organolithiums

Abstract

A convenient method for the synthesis of 2,4,8-trisubstituted 1,7-naphthyridines 6 by the reaction of (E)-4-(1-aryl-2-methoxyethenyl)-3-isocyanopyridines 4, which could be easily prepared from commercially available 3-aminopyridine via aroylation of lithium (4-lithiopyridin-3-yl)pivalamide with Nmethoxy-N-methylbenzamides, with excess organolithiums has been developed.

Synthesis of 2‐Aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones by Deprotective Cyclization of N‐{3‐[(2E)‐3‐Arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides in Water

“…Therefore, we embarked on the research on developing a novel and facile method for the preparation of 2,3‐dihydro‐1,8‐naphthyridin‐4(1 H )‐one derivatives. We previously reported that N ‐lithio‐ N ‐(4‐lithiopyridin‐3‐yl)‐2,2‐dimethylpropanamide reacted with N ‐methoxy‐ N ‐methylbenzamides to give N ‐(4‐aroylpyridin‐3‐yl)‐2,2‐dimethylpropanamide, from which 1,7‐naphthyridine and 3‐aryl‐3 H ‐pyrrolo[2,3‐ c ]pyridin‐3‐ol derivatives could be prepared. We envisioned the possibility of preparing N ‐{3‐[(2 E )‐3‐arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides 3 from N ‐lithio‐ N ‐(3‐lithiopyridin‐2‐yl)‐2,2‐dimethylpropanamide via reactions with (2 E )‐3‐arylprop‐2‐enals, followed by oxidation.…”