An Efficient Synthesis of Dibenzo[c,f]-2,7-naphthyridine Ring System through Design of Experiments

The dibenzo[ c, f ]-2,7-naphthyridine ring system was found to be of biological interest, but had limited synthetic accessibility. The initial compound of interest, 10,11-dimethoxy-4-methyldibenzo[ c, f ]-2,7-naphthyridine-3,6-diamine, was obtained in <25% yield by reacting 4-chloro-6,7-dimethoxy-quinoline-3-carbonitrile with 2-methyl-benzene-1,3-diamine. A reliable high-yielding procedure was identified through the use of design of experiments (DOE). The effects of stoichiometry of reagents, catalyst, and temperature were explored in this study. The DOE optimization suggested temperatures higher than the boiling point of our solvent. Hence, microwave heating was used, resulting in 80% yield of the desired product.