Synthesis of Methylpyridine Derivatives. XXVII. Synthesis of 1, 3-Disubstituted-4-oxo-quinolizine and 2, 4-Disubstituted-1-oxo-benzo [c] quinolizine Derivatives

Abstract

Reaction of ethyl α-(dimethylaminomethylene)-2-pyridineacetate (I) with acetic anhydride gives ethyl 4-oxo-4H-quinolizine-1-carboxylate (Va). Similar reaction with acid anhydrides, such as propionic anhydride and n-butyric anhydride, affords the corresponding 3-substituted-quinolizine derivatives (Vc and Ve). Similarly, α-(dimethylaminomethylene)-2-pyridineacetonitrile (II) and quinolyl homologous (III and IV) react with acid anhydrides to give the corresponding 3-substituted-4-oxo-4H-quinolizine-1-carbonitrile (Vb, Vd and Vf), ethyl 2-substituted-1-oxo-1H-benzo [c] quinolizine-4-carboxylate (VIa, VIc and VIe) and 4-carbonitrile derivatives (VIb, VId, and VIf), respectively. I reacts with diethyl malonate to give diethyl 4-oxo-4H-quinolizine-1, 3-dicarboxylate (Vg). Similar reaction with esters, such as ethyl cyanoacetate, ethyl acetoacetate and ethyl 2-pyridineacetate, affords the corresponding 3-substituted-quinolizine derivatives (Vi, Vk, and Vm). II, III and IV react with esters to form quinolizine and benzoquinolizine derivatives (Vh, Vj, Vn, VIg, VIh, VIi, VIj, VIk, and VIl). Reaction of III with esters affords ethyl 2-(2'-quinolyl)-1-oxo-1H-benzo [c] quinolizine-4-carboxylate (VII), besides the expected product (VIg, VIi, VIk). Reaction of IV with ethyl acetoacetate gives ethyl 3-(2'-quinolyl)-6-methyl-2-pyridone-5-carboxylate (IX) as a main product (33%).