Cyclisation of 2-Chloro- N -(2-Pyridinyl)Nicotinamides to 5-Oxo-5,6-Dihydrodipyrido[1,2- a :3′,2′- e ]Pyrimidin-11-Ium Chlorides

Abstract

The ease of thermal cyclisation of 2-chloro-N-(R-2-pyridinyl)nicotinamides, (5: X = NH) to 5-oxo-5,6-dihydrodipyrido-[1,2-a:3′,2′-e]pyrimidin-11-ium chlorides in solution has been found to be in the order: (5: X = NH; R = 4-Me) > (5: X = NH; R = 5-Me) > (5: X = H; R = 6-Me) > (5: X =NH; R = 3-Me). This order reflects both steric and electronic effects of the methyl groups. The products of the cyclisations, which were monitored by NMR spectroscopy in DMSO-d₆, were generally characterised by NMR spectroscopy and, specifically for 9-Me-5-oxo-5,6-dihydrodipyrido[1,2-a:3′,2′-e]pyrimidin-11-ium chloride, by X-ray crystallography. The crystal structure of 2-chloro-N-(6-methyl-2-pyridinyl)nicotinamide is also reported. The ester and thioester analogues, 2-pyridinyl 2-chloronicotinate and S-(2-pyridinyl) 2-chloro-3-pyridinecarbothioate, do not undergo cyclisation under the same conditions used for the amides.