Reactions of Alkyl (Z)-2-[(E)-2-Cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates with C- and N-Nucleophiles. The Synthesis of Fused 2H,5H-Pyran-2,5-diones, 4H-Pyrimidin-4-ones, and 1-Heteroaryl-1H-imidazole-4-carboxylates

Alkyl (Z)-2-[(E)-2-cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates (2) and (3) were transformed with C-and N-nucleophiles into alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-heteroarylpropenoates (10-13), 2H,5H-benzo-[b]pyran-2,5-diones (14) and (15), 2H,5H-pyrano[4,3-b]pyran-2,5dione (16), 2H,5H-pyrano[3,2-c]benzo[b]pyran-2,5-dione (17), alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-arylamino-(28-40), and 3-heteroarylaminopropenoates (41-43), pyrido[1,2-a]pyrimidin-4-ones (50-53), thiazolo[3,2-a]pyrimidin- 4-one (54), benzothiazolo[3,2-a]pyrimidin-4-one (55), and 1-heteroaryl-1H-imidazole-4-carboxylate (56).Compounds (28-43) exist in (2E, 2'E) form or as a mixture of (2E, 2'E) as a major and (2Z,2'E) form as a minor isomer.α-Amino acids and their derivatives play an important role in organic synthesis, 1-6 especially as building blocks for the preparation of many heterocyclic systems.Recently, several comprehensive reviews have been published describing the preparation of the following heterocyclic systems: pyranones and fused pyranones, 7 fused pyridinones, 8 fused pyrimidinones, 9 pyrroles, 10 pyrazoles, 11 imidazoles, 12 and 1,2,4- oxadiazoles. 13Quinolizines, pyridopyrimidines, benzopyrans, pyranopyrans and related fused systems are the basic structures of many alkaloids and their synthetic derivatives exhibiting various biological activity. 14-18 Since there has been no general method known for the preparation of those heterocyclic systems, in which an amino acid is incorporated or partially incorporated into the heterocyclic ring, we have prepared a series of 2-substituted 3-dimethylaminopropenoates, 2-[(2,2-disubstituted ethenyl)amino]-3-dimethylaminopropenoates and related compounds, stable masked 2-formylglycine derivatives, as versatile reagents for the preparation of various heterocyclic systems, 19 among others alkyl 3,4-disubstituted and alkyl 1-acyl-3,4-disubstituted pyrrole-2-carboxylates, 20,21 and dialkyl 3-aminopyrrole-2,4-dicarboxylates, 22 which have been further transformed into 5H-pyrrolo[3,2-d]pyrimidine derivatives, 23 and other systems, 24-30 including some natural products, such as aplysinopsins. 31 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. 28,32,33The substituents attached at 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. 19 Recently, alkyl(3) have been prepared from 2-pyridinylacetonitrile (1) in three steps (Scheme 1) and converted by heating in acetic acid into substituted 3-aminopyrrole-2-carboxylates and by treatment with aliphatic amines into 5H-pyrrolo[3,2-d]pyrimidin-4-ones. 34Scheme 1 2 (R = Me) 3 (R = Et) N COOR Me 2 N H H H CN N N CN 1 1.CH(OEt) 3 , acetonitrile, ZnCl 2 , ∆ 2. ROOCCH 2 NH 2 xHCl, Et 3 N, EtOH, rt (R=Me,Et) 3. tert-Butoxy-bis(dimethylamino)methane (Bredereck's reagent), toluene, ∆ In this paper we report the transformations of compounds (2) and (3), with C-and N-nucleophiles into βheteroaryl-, β-arylamino-and β-heteroarylamino-α,β-didehydro-α-amino acid derivatives, and various heterocyclic systems in which heteroaryl and cyano substituted ethenylamino groups are introduced into the newly formed ring.Compounds (2) and (3) were treated with barbituric (4) and thiobarbituric acid (5) in acetic acid at room temperature for 1.5 to 2 h to form the corresponding 2-[2-cyano-2-(2-pyridinyl)ethenyl]aminopyrimidinyl-propenoates (10-13) in 54-91% yield.By treatment with cyclohexane-1,3-diones (6) and (7) in acetic acid under reflux for several hours 5,6,7,8-tetrahydro-2H,5H-benzo[b]pyran-2,5-diones (14) and (15) were obtained in 27-48% yield.4-Hydroxy-6-methyl-2H-pyran-2-one (8) and 4-hydroxy-2H-ben-zo[b]pyran-2one (9) afforded 2H,5H-pyrano[4,3-b]pyran-2,5-dione (16) and 2H,5H-pyrano[3,2-c]ben-zo[b]pyran-2,5dione (17) derivatives in 47-58% yield.(Scheme 2).