ChemInform Abstract: Reactions of Alkyl (Z)‐2‐[(E)‐2‐Ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl] amino‐3‐dimethylaminopropenoates with C‐ and N‐Nucleophiles. The Synthesis of Fused Pyranones, Pyridinones and Pyrimidinones.

Abstract

Alkyl 2-[2-ethoxycarbonyl-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates 3 and 4 were transformed with C-and N-nucleophiles into β-heteroaryl-α,β-didehydro-α-amino acid derivatives 13-16, substituted 3-amino-4H-quinolizin-4-one 17, 2H,5H-benzo [b]pyran-2,5-dione 18 and 19, 2H,5H-pyrano [4,3-b]pyran-2,5-dione 20, 2H,5H-pyrano[3,2-c] Quinolizines, pyridopyrimidines, benzopyrans, pyranopyrans and related fused systems are the basic structures of many naturally occurring alkaloids and their synthetic derivatives exhibiting various biological activity [1][2][3][4][5].Recently, alkyl 2-substituted 3-(dimethylamino)propenoates and their cyclic analogs have been shown to be versatile and efficient reagents for the preparation of various heterocyclic systems [6], including some natural products, such as aplysinopsins and analogs [7]. This methodology has opened also an easy access to substituted 4H-quinolizin-4-ones, pyridopyrimidines and other heterocyclic systems with an amino group in 3 position of the newly formed heterocyclic system [8][9][10]. The substituents attached at the 2,2-disubstituted ethenyl group of the substituted amino group are ester groups or a combinations of an ester and an acyl, two acyl, an ester and an amino, an ester and a cyano, two cyano, or an ester and a phenyl group [6].In this communication we report the transformations of 2-[2-ethoxycarbonyl-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates 3 and 4, prepared from ethyl 2-pyridinylacetate (1) in two steps (Scheme 1) [11], with Cand N-nucleophiles in order to introduce a heteroaryl substituted ethenylamino group into the newly formed heterocyclic system.amino-3-dimethylaminoprope-noates 3 and 4 were treated with barbituric acid (5) or its 1,3-dimethyl derivative (6) in acetic acid at room temperature for 3-5 hours or at 80°C for 0.5-2.5 hours to form the corresponding 2-[2-ethoxycarbonyl-2-(2-pyridinyl)ethenyl]amino-3-(4-hydroxy-2,6-dioxo-5-pyridinyl)propenoates 13-15 in 65-94% yield, and with indole (7) at room temperature for 6 days the corresponding 3-(3-indolyl)propenoate 16 in low yield. By treatment of 3 or 4 with other C-nucleophiles in acetic acid at room temperature, 80-100 °C or by refluxing for several hours the cyclic products, such as fused pyranones, pyridinones, pyrimidinones, and N-heteroaryl substituted imidazoles were obtained. In this respect, 3 and/or 4 were transformed with 2-pyridinylacetonitrile (8)