9‐Hydroxy‐2‐methyl‐4H‐pyrido[1,2‐α] pyrimidin‐4‐one and its derivatives

2‐Amino‐3‐( o ‐bromobenzyloxy)pyridine ( 1 ) and ethyl acetoacetate gave 9‐( o ‐bromobenzyl‐oxy)‐2‐methyl‐4 H ‐pyrido[1,2‐α]pyrimidin‐4‐one ( 2 ) in 2% yield. When 1 and methyl β‐amino‐crotonate ( 3 ) were reacted, benzyl ether cleavage occurred and the products were 9‐hydroxy‐2‐methyl‐4 H ‐pyrido[1,2‐α]pyrimidin‐4‐one ( 4 ) and its ammonium salt ( 5 ). These observations led to an alternative synthesis in which 2‐amino‐3‐pyridinol ( 6 ) and either 3 or methyl acetoacetate, ( 8 ) in diethylbenzene at 185° gave 4 in 86 and 87% yields, respectively, and the anion of 4 and o ‐bromobenzyl bromide gave 2 in 61% yield. Even in diethylbenzene at 185°, 1 and 8 gave only trace amounts of 2 . Thus, o ‐bromobenzylation of the 3‐hydroxyl group in 6 markedly decreased the reactivity of the amino group in 6 toward reactions with acetoacetic esters.