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A 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. The availability of inexpensive 2-aminopyridines and a 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 calculations. Products are obtained in up to 95% yield.

An efficient synthesis of novel 2,3-dihydro-4H-pyrido[1,2-a]pyrimidin-4-ones has been reported. Inexpensive and readily available substrates, environmentally benign reaction condition, and product formation up to quantitative yield are the key features of this methodology. Products are formed by the aza-Michael addition followed by intramolecular acyl substitution in a domino process. The polar nature and strong hydrogen bond donor capability of 1,1,1,3,3,3-hexafluoropropan-2-ol is pivotal in this cascade protocol.