| The quinazoline skeleton is widely present in various alkaloids and organic molecules with biopharmacological activity.It has been used in the field of anti-malarial parasites and antibacterial.In recent decades,targeted therapeutic drugs have become more and more popular.Individual quinazoline derivatives have become targeted drugs for anti-tumor.It is precisely because of their superior backbone and biological activity that they have become the research target.The functional groups of quinazoline were modified,different substituents and other skeletons were introduced,and the quinazoline derivative library was expanded to pave the way for subsequent screening of biologically active substances.On the other hand,the 1,3-dipolar active and quinazoline compounds have nitrogen-directed groups,which can carry out high stereoselective cycloaddition,and can also introduce different groups on the 2-aryl group through C-H activation.For example,halogen,alkyl,alkoxy and the like.In this thesis,quinazoline-3-oxide and 2-arylquinazolinone are used as raw materials.Through the 1,3-dipolar [3 + 2] cycloaddition or metal-catalyzed coupling,etc.Quinazoline and quinazolinone ring expansion(five-membered heterocycle and seven-membered heterocyclic ring),azide was introduced at the C4 position of quinazoline,and a series of quinazoline derivative structures were constructed.The research content is specifically divided into the following three parts:(1)Isoxazolo [2,3-c] quinoline was synthesized from 1,3-dipolar [3+2] cycloaddition using quinazoline-3-oxide and methyl 3-methoxyacrylate Oxazoline.The reaction does not require a catalyst,the temperature is moderate,and it has an efficient stereoselectivity.(2)Using 2-o-bromoarylquinazoline and o-bromophenol as raw materials,under the catalysis of cuprous,tandem C-O(S)/ C-N can effectively synthesize dibenzoxazaquinazolinone.The reaction substrate has good adaptability and high yield.(3)Using 2-arylquinazolinone as the raw material and sodium azide as the azide reagent,the synthesis of 4-azidoquinazoline was developed.Can be carried out under mild conditions to obtain a series of azide-containing quinazoline derivatives. |
