1,6- and 1,7-naphthyridines. II. Synthesis from acyclic precursors

✍ Scribed by M. Mercedes Blanco; Isabel A. Perillo; Celia B. Schapira

• Publisher: Journal of Heterocyclic Chemistry
• Year: 1999
• Tongue: English
• Weight: 370 KB
• Volume: 36
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570360425

✦ Synopsis

Abstract

A number of 8‐hydroxy‐6‐methyl‐1,6‐naphthyridin‐5(6__H__)‐one‐7‐carboxylic acid alkyl esters 3 and the isomeric 5‐hydroxy‐7‐methyl‐1,7‐naphthyridin‐8(7__H__)‐one‐6‐carboxylic acid alkyl esters 4 were synthesized from acyclic precursors obtained starting from quinolinic anhydride 5. Thus, methanolysis of 5 afforded the hemiester 6 which treated with oxalyl chloride and sarcosine ethyl ester gave 3‐(N‐ethoxycarbonylmethyl‐N‐methylcarbamoyl)pyridine‐2‐carboxylic acid methyl ester 8. Compound 8 was cyclized to naphthyridines 3a‐e with sodium alkoxides. The isomeric naphthyridines 4a‐c were obtained by cyclization of the open intermediary 2‐(N‐ethoxycarbonylmethyl‐N‐methylcarbamoyl)pyridine‐3‐carboxylic acid methyl ester 9 obtained by a route that involves treatment of 5 with sarcosine ethyl ester and esterification with diazomethane. Spectroscopic properties (^1^H nmr, uv, ir) of compounds 3 and 4 are discussed and confirmed the proposed structures.