Metal-catalyzed Amination And Acylation Of Quinazolin-4-one

Quinazolin-4-ketones are a class of important organic compounds,with a wide range of pharmacological and biological activities,such as:antibacterial,anti-cancer,antiviral.The direct amination and acylation products of quinazolin-4-one as raw materials have important application prospects in the fields of medicine and biopharmaceuticals.In this paper,by referring to relevant literatures,the amination and acylation of quinazoline-4-ketone with cheap metal catalysis were realized.Through a series of experimental studies,the reaction strategy was proved to be a kind of efficient,cheap and simple synthesis method.In the first chapter,the research progress of quinazoline-4-ketones is briefly reviewed.In the second chapter,fatty amines,quinazoline-4-ketones,hydroxy pyridines or pyrimidines are used as raw materials,DMF is used as solvent,copper acetylacetone is used as catalyst,DTBP is used as oxidant.The reaction is carried out at 100℃.After 10 hours,4-amino-quinazoline products can be obtained with a high yield.In this chapter,we synthesized 40 compounds and proposed the correct reaction mechanism.At the same time,we used this reaction system to synthesize an analog of the anticancer drug NVP-LDE225.#12In the third chapter,we take quinazoline-4-ketones,benzaldehyde or aliphatic aldehydes as raw materials,acetonitrile as solvent,ferric chloride as catalyst,TBHP as oxidant,and the reaction is reacted at 80℃ for 5 hours to obtain acylated products with a high yield.In this chapter,we synthesized a total of 29 compounds and conducted a series of control experiments to put forward the correct reaction mechanism.#12At the same time,the amination and acylation products of all quinazoline-4-ketones are determined by NMR,MS and IR spectra.The amination products 4c and 41 of quinazoline-4-ketones and the acylation products 3a and 5a of quinazoline-4-ketones are cultured in single crystal and determined by single crystal diffraction.