Hexafluoroisopropanol mediated benign synthesis of 2H-pyrido[1,2-a]pyrimidin-2-ones by using a domino protocol

Abstract

Domino strategy has been used for the synthesis of 2H-pyrido[1,2-a]pyrimidin-2-ones. Four sequential reactions: aza-Michael addition, water elimination, intramolecular acyl substitution, and [1,3]-H shift were observed in this domino protocol. Hexafluoroisopropanol is used as a promotor and recyclable solvent in this cascade process. Availability of inexpensive 2-aminopyridines and wide variety of Michael acceptors such as commercially available acrylates and unactivated Baylis-Hillman adducts makes this methodology a huge reservoir of novel fused N-heterocycles as bioactive and potential therapeutic agents. The reaction mechanism has been proposed and rationalized by density functional theory calculation. Products are obtained up to 95% yield.

Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii

“…In our quest to develop novel methodologies to synthesize bioactive molecules [23,24,25,26], we have reported the synthesis of novel pyrazole derivatives as potent antimicrobial agents [27,28,29]. Based on our lead molecules and known pharmacological properties of coumarin derivatives, we designed the novel molecules hoping to produce potent antimicrobial agents (Figure 1).…”

Synthesis and Antimicrobial Studies of 4-[3-(3-Fluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic Acid and 4-[3-(4-Fluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic Acid as Potent Growth Inhibitors of Drug-Resistant Bacteria

“…In our pursuit to find novel small-molecule heterocycles, − we have reported the synthesis and antimicrobial activities of several pyrazole-derived hydrazones. − Based on our reported molecules, we designed and synthesized fluorine-substituted aldehydes to synthesize hydrazone derivatives for antimicrobial studies. Fluorine substitution has been extensively studied in drug discovery to enhance the biological activity and increase the chemical and metabolic stability of the resultant molecules .…”

Hexafluoroisopropanol-Mediated Domino Reaction for the Synthesis of Thiazolo-androstenones: Potent Anticancer Agents

“…In our quest to synthesize bioactive molecules − and to develop new domino reactions to synthesize heterocycles, , we planned the synthesis of thiazolino-androstanedione derivatives by using our recently reported methodology, the synthesis of thiazoline derivatives ( 2 ) by reacting thioamides with γ-bromoenones ( 1 ) . Reaction of 6β-bromoandrostenedione ( 3 ) with thiourea derivatives formed aminothiazoloandrostenone derivative ( 4 ) by an unexpected mechanism .…”