Synthesis of 3-methyl and 7-methyl regio isomers of medorinone

Article abstract of DOI:10.1055/s-1991-26604

Reaction of 3-aminocrotononitrile (2) with methyl methacrylate (3) and methyl 2-propynolate (9) led to the formation of 1,4,5,6-tetrahydro-2,5-dimethyl-6-oxo-3-pyridinecarbonitrile (4) and 1,6-dihydro-2-methyl-6-oxo-3-pyridinecarbonitrile (10), respectively. Condensation of 4 with Bredereck's reagent [bis(dimethylamino)tert-butoxymethane], and that of 6-methoxy-2-methyl-3-pyridinecarbonitrile (12) with N,N-dimethylacetamide dimethyl acetal gave the corresponding enamines 5 and 13 which in turn were cyclized with hydrogen bromide to bromonaphthyridinones 6 and 14, respectively. Debromination of 6 followed by dehydrogenation gave 3-methyl-1,6-naphthyridin-2(1H)-one (8). Debromination of 14 with catalytic reduction gave 7-methyl-1,6-naphthyridin-2(1H)-one (15).