4-[3-Dimethylamino-1-(2-dimethylaminovinyl]prop-2-enylidene]-2-phenyl-1,3-oxazol-5(4H)-one and 5-[3-Dimethylamino-1-(2-dimethylaminovinyl)prop-2-enylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one in the Synthesis of 1,4-Dihydropyridine Derivatives

4-{3-Dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-2phenyl-1,3-oxazol-5(4H)-one (3) and 5-{3-dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-3-methyl-2-thioxo-1,3-thiazolidin-4-one (15) were prepared from 4-(1-methylethylidene)-2-phenyl-1,3-oxazol-5(4H)-one (2) and 5-(1-methylethylidene)-2-thioxo-1,3-thiazolidin-4-one (11), respectively.Treatment of compounds (3) and (15) with primary amines afforded 1,4-dihydropyridine derivatives (5) and (16) in 19-94% yields.Reactions of oxazolones (5) with hydrazine hydrate gave the corresponding imidazolones (6), while upon base-or acid-catalysed methanolysis of 5 methyl (benzoylamino)(1-substituted pyridin-4(1H)-ylidene)acetates (7) were obtained.Catalytic hydrogenation of 7a furnished α-(piperidin-4-yl)glycine derivative (8) and/or α-(pyridin-2-yl)glycine derivative (9).The interest in dihydropyridines is due to the unique ability of these compounds to act as NAD(P)H analogues of 1,4-dihydronicotinamide. 1 They are most extensively studied as calcium antagonists, 2 however, they also exhibit hepatoprotective, 3 antitumor, 4 antidiabetic, 5 bronchodilating, 6 and other pharma-cological activities 7-9 (Figure 1). Figure 1.Examples of Pharmacologically Important 1,4-Dihydropyridine Derivatives.H N Me Me NO 2 MeOOC COOMe Nifedipine (calcium channel blocker) H N Me Me O Cl Cl Clopidol (antiparasitic) N O COOH N Ciprofloxacin (antibiotic) HN F1][12][13] The most widely used method is Hantzsch-type cyclocondensation reaction 11,12 (Scheme 1). Scheme 1.Hantzch Three-Component Synthesis of 1,4-Dihydropyridines.