Syntheses of some highly substituted pyridines, 2,7-naphthyridines and 1H-pyrimido[4,5,6-i,j][2,7]naphthyridines

Abstract

2-Cyanomethyl-1,1,3,3-propenetetracarbonitrile is cyclised by halogen acids in acetone to 2-amino-4-cyanomethyl-6-halogeno-3,5-pyridinedicarbonitrile, although the 6-iodopyridine further reacts with acetone to give 2-amino-4-(1-cyano-4-hydroxy-2,4-dimethylpent-1-en-1-yl)-6-iodo-3,5-pyridinedicarbonitrile. The α-halogen atom of these pyridines has been replaced by a variety of nucleophiles. These 4-cyanomethyl-3,5-pyridinedicarbonitriles cyclise further in the presence of methoxide ion, to produce substituted 2,7-naphthyridine-4-carbonitriles. 2-Amino-6-chloro-4-cyanomethyl-3,5-pyridinedicarbonitrile on cyclisation gives 1,8-diamino-3,6-dimethoxy-2,7-naphthyridine-4-carbonitrile as the sole product, whereas 2-amino-6-p-anisidino-4-cyanomethyl-3,5-pyridinedicarbonitrile yields a mixture of 1,8-diamino-3-p-anisidino- and 3,8-diamino-1-p-anisidino-6-methoxy-2,7-naphthyridine-4-carbonitriles in the ratio 1 : 8. A mechanism to account for these alternative cyclisations is proposed.

1,8-Diamino-2,7-naphthyridines, on reaction with carbonyl derivatives such as orthoesters, aliphatic and aromatic aldehydes, alicyclic ketones, esters, and carboxylic acid anhydrides, yield derivatives of the novel pyrimido-[4,5,6-i,j][2,7]naphthyridine system, or, in the case of the reaction with phthalic anhydride, a derivative of the pentacyclic isoindolo[2,1-a]pyrimido[4,5,6-i,j][2,7]naphthyridine system.