One Pot Synthesis of Novel Cyanopyridones as an Intermediate of Bioactive Pyrido[2,3-d]Pyrimidines

Abstract

Synthesis, structural characterization, and biological activity studies of novel pyrido [2,3-d]pyrimidines (10a−h, 11a−h) are described. Cyclization of cynoacetamides (4, 5) with malonitrile (7) and aldehyde (6a−h) via Hantzsch pyridine synthesis afforded cyanopyridones (8a−h, 9a−h), which on cyclization with formic acid under microwave conditions led to the final product. All the reactions are significantly faster and the isolated yields are remarkably higher in microwave conditions compared to the conventionally heated reactions. The compounds were tested in vitro for their antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtillus, Staphylococcus aureus, and Micrococcus luteus and antifungal activity against Trichphyton longifusus, Candida albicans, Microsporum canis, Fusarium solani. Compounds 10b, 10e, 11b and 11e exhibited good antibacterial and antifungal activities compared with standards.

Synthesis and synthetic applications of cyanoacetamides

“…Elimination of ethanol yields the isolable pyridine-2,6-diones 210a-f (Scheme 87, The 6-amino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles 211a-h and 212a-h were prepared by reacting cyanoacetamides 3a and 3co with aldehydes 13 and malononitrile 20a via Michael addition reaction (Scheme 88, Table 38). 13…”

“…The reaction of compounds 3ez and 3fa with salicylaldehyde 13aa in acetic acid at reflux led to the synthesis of the corresponding chromene derivatives 302a and 302b in moderate yields (Scheme 139, Table 51 The 2-cyano-N-(pyrazol-4-yl)acetamide derivatives 3az1 and 3az2 underwent intramolecular cyclization under reflux in DMF containing anhydrous sodium acetate to give either 307a,b or their isomers 308a,b. Compounds 308a,b were assigned to be the formed products based on its 13…”

Impact of an aryl bulky group on a one-pot reaction of aldehyde with malononitrile and N-substituted 2-cyanoacetamide

“…We performed this reaction via a one-pot strategy, which has been reported in many reactions, [5][6][7][8] because it has certain advantages based on green chemistry concepts such as the reduction of chemical waste, workup procedure, purication process, and time, which make the reaction greener. 9 In the literature, the one-pot reaction of aryl aldehyde, malononitrile and N-substituted 2-cyanoacetamide is mostly reported to use piperidine [10][11][12] as a catalyst. Other bases, such as potassium carbonate 13 and triethylamine, 14 have also been reported.…”

Synthesis of novel bis(dihydropyridine) and terpyridine derivatives

“…MCRs offer the advantage of simplicity, selectivity, atom-economy and synthetic efficiency over conventional chemical reactions. [22][23][24][25][26] Although the synthesis of biologically interesting 1,2dihydropyridine-3,5-dicarbonitrile derivatives has been investigated in the past, [27][28][29][30][31] there is still demand for more concise and efficient elucidation of molecular structure. In connection with this finding and in continuation to our work on Michael addition, [32][33][34][35][36][37][38] multicomponent reactions, [35][36][37][39][40][41][42][43][44][45] as well as on the synthesis of bis-heterocycles, 41,[45][46][47][48][49][50][51][52][53][54] we report herein on the synthesis of novel bis(1,2-dihydropyridine-3,5dicarbonitriles) and terpyridines utilizing 2-cyanoacetamide derivatives as intermediates.…”