A FACILE AND NOVEL SYNTHESIS OF 1,6-NAPHTHYRIDIN-2(1H)-ONES

• Published in: Journal of heterocyclic chemistry Vol. 27; no. 7; pp. 2085 - 2091
• Main Authors: SINGH, B, LESHER, GY
• Format: Journal Article
• Language: English
• Published: TAMPA HETERO CORPORATION 01.11.1990
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; MILRINONE; POTENT CARDIAC BIPYRIDINE
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570270743

A new and convenient procedure for the synthesis of 1,6-naphthyridin-2(1H)-ones and their derivatives is described. In the first scheme 5-acetyl-6-[2-(dimethylamino)ethenyl]-1,2-dihydro-2-oxo-3-pyridinecarbonitrile (4) obtained by the reaction of N,N-dimethylformamide dimethyl acetal with 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (3) was cyclized to 1,2-dihydro-5-methyl-2-oxo-1,6-naphthyriridine-3-carbonitrile (5) by the action of ammonium acetate. Thermal decarboxylation of acid 7 obtained from the hydrolysis of nitrile 5 led to a mixture of 5-methyl-1,6-naphthyridin-2(1H)-one (8) and its dimer 9. Hydrazide 11 obtained from nitrile 5 in two steps was converted to 3-amino-5-methyl-1,6-naphthyridin-2(1H)-one (12) by the Curtius rearrangement. The amino group of 12 was readily replaced by treatment with aqueous sodium hydroxide to yield 3-hydroxy-5-methyl-1,6-naphthyridin-2(1H)-one (13). In the second scheme, Michael reaction of enamines of type 20 with methyl propiolate, followed by ring closure gave 5-acyl(aroyl)-6-methyl-2(1H)-pyridinones (21) which in turn were treated with Bredereck's reagent to produce 5-acyl(aroyl)-6-[2-(dimethyl-amino)ethenyl]-2(1H)-pyridinones (22). Treatment of 22 with ammonium acetate led to the formation of 1,6-naphthyridin-2(1H)-ones 23.