Synthesis of Aminonicotinonitriles and Diaminopyridines through Base-Catalyzed Ring Transformation of 2H-Pyran-2-ones

Abstract

An efficient and convenient synthesis of 2-amino-6-aryl-4-methylsulfanylnicotinonitriles (2), 2-amino-6-aryl-4-substituted-aminonicotinonitriles (4), and 2-amino-6-aryl-4-substituted-aminopyridines (6) has been delineated and illustrated through base-catalyzed ring transformation of 6-aryl-3-cyano-4-methylsulfanyl/substituted-amino-2H-pyran-2-ones (1, 3, and 5) with cyanamide and ammonium carbonate separately.

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

“…In both cases a subsequent oxidation step is usually required to convert the initially formed dihydropyridine intermediate into the desired aromatic pyridine. Some additional but much less common methods utilising cycloadditions of electron-rich oxazoles and acrylates [17–18] tri- and tetrazines with alkenes/alkynes [19] or pyrones with nitriles [20] have been used successfully to access specifically functionalised pyridines which are difficult to prepare by the more direct condensation routes.…”

New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage

“…amino-2-oxo-2 H -pyran-3-carbonitriles 1 was obtained by amination25 of 6-aryl-4-methylthio-2-oxo-2 H -pyran-3-carbonitriles by various secondary amines in refluxing ethanol (Fig. 1)262728. Synthesis of highly functionalized benzo[ h ]quinolines was carried out by stirring an equimolar mixture of 6-aryl-4- sec.…”

Base mediated regioselective synthesis of highly functionalized conjugated enones

“…Path a was proposed because use of malononitrile as a carbanion source provides 3-amino-5-sec.amino-[1,1'-biaryl]-2,4-dicarbonitriles as per earlier report. 22 In order to get 3'-amino-5'-sec.amino-1,2'-terphenyl-4'-carbonitriles, we have performed the reaction under nitrogen atmosphere, but failed and isolated mixture of two isomeric compounds which act as intermediate precursor for oxidative decyanation. In order to isolate the proposed intermediate, we have stirred the mixture of 2-oxo-4-piperidin-1-yl-6-thiophen-2-yl-2H-pyran-3-carbonitrile and benzylcyanide in DMSO in presence of KOH at room temperature under nitrogen atmosphere and isolated mixture of two isomeric compounds characterized as (2E,5Z)-2-phenyl-5-(piperidin-1-yl)-3-(thiophen-2-yl)hepta-2,5-dienedinitrile and (2E,4E)-2-phenyl-5-(piperidin-1-yl)-3-(thiophen-2-yl)hepta-2,4-dienedinitrile (Scheme 5).…”