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Upstream product

• 23443-10-9 pyrido[1,2-a]pyrimidin-4-one 
• 402-43-7 p-trifluoromethylphenyl bromide 
• 1198413-23-8 3-chloro-4H-pyrido[1,2-a]pyrimidin-4-one 
• 128796-39-4 4-trifluoromethylphenylboronic acid 

Relevant academic research and scientific papers

Pd-Catalyzed Ag(I)-Promoted C3-Arylation of Pyrido[1,2-a]pyrimidin-4-ones with Bromo/Iodo-Arenes

A regioselective Ag(I)-promoted Pd-catalyzed C3-H activation-arylation of pyrido[1,2-a]pyrimidin-4-ones with bromo/iodo-(hetero)arenes under aqueous conditions has been developed. It affords an efficient access to pharmaceutically important versatile 3-aryl-pyrido[1,2-a]pyrimidin-4-ones. Interestingly, the arylation undergoes via a pathway with an unusual feature involving the formation of cationic arylpalladium species promoted by halo-sequestering Ag salts enabling concerted C3-palladation-deprotonation, as explored by relevant experiments and spectroscopic studies. The present approach is step economical, good yielding, and compatible with various functionalities and applicable to a wide range of starting materials.

Scaffold-hopping of bioactive flavonoids: Discovery of aryl-pyridopyrimidinones as potent anticancer agents that inhibit catalytic role of topoisomerase IIα

A strategy of scaffold-hopping of bioactive natural products, flavones and isoflavones, leading to target-based discovery of potent anticancer agents has been reported for the first time. Scaffold-hopped flavones, 2-aryl-4H-pyrido[1,2-a]pyrimidin-4-ones and the scaffold-hopped isoflavones, 3-aryl-pyrido[1,2-a]pyrimidin-4-ones were synthesized via Pd-catalyzed activation–arylation methods. Most of the compounds were found to exhibit pronounced human topoisomerase IIα (hTopoIIα) inhibitory activities and several compounds were found to be more potent than etoposide (a hTopoIIα-inhibiting anticancer drug). These classes of compounds were found to be hTopoIIα-selective catalytic inhibitors while not interfering with topoisomerase I and interacted with DNA plausibly in groove domain. Cytotoxicities against various cancer cells, low toxicity in normal cells, and apoptotic effects were observed. Interestingly, compared to parent flavones/isoflavones, their scaffold-hopped analogs bearing alike functionalities showed significant/enhanced hTopoIIα-inhibitory and cytotoxic properties, indicating the importance of a natural product-based scaffold-hopping strategy in the drug discovery.

Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-ones

The palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-one with (het)arylboronic acids allow easy access to (het)aryl and vinyl derivatives of this bicycle in good to excellent yields, even from chloro derivatives. The sequence of reactivity of the halogen in the different positions of the ring system was also investigated. 6-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one could be prepared by thermal cyclization of isopropylidene (6-phenylpyrid-2-ylamino)methylenemalonate, together with a small amount of 7-phenyl-1,4-dihydro-1,8-naphthyridin-4-one.