Study On The Synthesis Of Novel 4H-Pyrido[1,2-a]pyrimidin-4-one Derivatives

The study of 4H-pyrido[1,2-a]pyrimidin-4-one and its derivatives began in the 1960s.Because of their various biological activities,good pharmacokinetic characteristics and low toxicity,a number of pharmaceutical companies have developed a number of listed drugs.For example,risperidone,palperidone and pilomperone,which have antipsychotic activity,and Evrysdi ^TMdrugs,which are used to treat Spinal Muscular Atrophy in patients with 2 months or more.Therefore,it is necessary to develop more direct and effective synthesis methods to construct 4H-pyrido[1,2-a]pyrimidin-4-ones substituted by different functional groups.The direct oxidative coupling reaction between C-H bonds can avoid the prefunctionalization of coupling substrates and unnecessary waste of raw materials,which fully embodies the principle of atomic economy.In this paper,novel 4H-pyrido[1,2-a]pyrimidin-4-one derivatives substituted by different functional groups were synthesized efficiently and controllably through C-H bond activation strategy.The research content mainly includes the following two parts,specifically as follows:In the first part,a novel Ag NO₃-catalyzed cross-dehydrogenation coupling reaction between 4H-pyrido[1,2-a]pyrimidin-4-ones and dialkyl phosphates was developed to construct C-P bond.The reaction used4H-pyrido[1,2-a]pyrimidin-4-ones and dialkyl phosphates as substrates,Ag NO₃as catalyst,acetonitrile as solvent,and reacted at 80℃for 12hours.AseriesofC3positionphosphorylated4H-pyrido[1,2-a]-pyrimidin-4-ones were obtained with yields of67%-91%.The reaction exhibited the advantages of high efficiency,high selectivity,and good functional group tolerance.Among them,the fluorescence of compound 3u was studied,which could be used as a fluorescent probe for the identification of Fe³⁺.In the second part,a novel NIS-catalyzed reaction with4H-pyrido[1,2-a]p-yrimidin-4-ones and diaryl diselenides was developed to construct the C-Se bond.A series of C3 position selenylated4H-pyrido[1,2-a]-pyrimidin-4-ones were obtained with yields of74%-97%.The reaction shown the advantages of mild condition,high yield,good selectivity,and avoiding the environmental pollution caused by the use of metal catalysts.At the same time,this method could be used in the reaction of 4H-pyrido[1,2-a]pyrimidin-4-one to construct C-S bond.