Enamines derived from the reactions of 2-amino-3-(o-bromobenzyloxy)pyridine with esters of acetoacetic and β-aminocrotonic acids. Enamines as intermediates in the formation of 4H-pyrido[1,2-a]pyrimidin-4-ones

Two stable crystalline enamines, 10 and 11 , have been isolated from the reactions of 2-amino-3-(o-bromobenzyloxy)pyridine, 4 , with esters of acetoacetic or β-aminocrotonic acids. The formation of 10 and 11 occurred in the absence of a solvent or in diethylbenzene at 100–175°, and was always accompanied by the formation of the cyclized derivative, 9-(o-bromobenzyloxy)-2-methylpyrido[1,2-a]pyrimidin-4-one, 12. Molecular models, ir, and pmr spectra were employed to establish the structure of the enamines and to demonstrate that in solution, 10 and 11 existed as six-membered chelate structures, with intramolecular hydrogen bonding between the NH proton and the ester carbonyl oxygen atom. The thermal cyclization of 10 and 11 to 12 occurred under a variety of conditions: (a) in diethylbenzene at 170–175°, (b) fusion at 175–180° under atmospheric pressure, or (c) heating at 175–180°/1 mm, thus suggesting that an enamine is the intermediate in cyclization reactions that lead to the formation of pyrido [1,2-a]pyrimidin-4-ones.