Study On The Double Michael Addition Reaction Of Dihydropyrrolo[2,3-d] Pyrimidin-6-ones And Dienones To Construct Spirocyclic Pyrrolopyrimidines With High Stereoselectivity

Pyrrolopyrimidine heterocyclic compounds^[1],as the basic skeleton of many drug molecules and natural products,they have biological activities such as antiviral,bactericidal,and anticancer.And it has a significant effect on many drug-resistant diseases,of which small molecule inhibitors are the most used,but drugs with pyrrolopyrimidine skeletons are not clinically extensive enough,so the development of new pyrrolopyrimidine skeletons The lead compound has broad application prospects.Dienone compounds are often used as effective organic synthesis building blocks to achieve a variety of different synthetic transformations.Dienone compounds are rich in types and can be widely involved in various organic synthesis tasks.Therefore,this article chooses Dienone compounds are used for structural transformation and modification of pyrrolopyrimidine compounds.The reaction process is Michael addition reaction.Michael reaction is a very important type of organic reaction,which is often used for carbon chain growth and synthesis.Compounds with various functional groups,but in the Michael addition reaction,relatively expensive catalysts are often used,and the reaction conditions are relatively harsh,so the development of mild and low-cost experimental methods has become a major goal of exploration.The later experiments were carried out under heterogeneous conditions,so a phase transfer catalyst was designed and used to promote the reaction.A cheap and easily available phase transfer catalyst and alkali were added to the reaction.There was no need to heat during the reaction,and a very high yield was obtained.Yield,this convenient and efficient method makes the synthesis of this type of pyrrolopyrimidine compounds have certain practical significance.Based on the previous research of the research group,this paper uses different kinds of benzaldehyde as raw materials to synthesize a series of 1,4-diene-3-ketone derivatives.In addition,it is designed to use 4-chloro-5,7-dihydro-6H-pyrrole And[2,3-d]pyrimidin-6-one is the starting material for the reaction,and4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ketone is active on the 5-carbon Methylene can be used as a Michael addition donor,and（1E,4E）-1,5-diarylpentan-1,4-diene-3-ketone undergoes two Michael additions to form a spiro compound.During this period,how to use alkali and phase transfer catalyst to efficiently catalyze 4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ketone and（1E,4E）-1,5-diarylpentan-1,4-di-en-3-ketone The Michael addition of,5-diarylpentan-1,4-diene-3-ketone,and the base,phase transfer catalyst,reaction time and solvent were screened on the reaction conditions,and the optimal conditions were finally determined.After that,the scope of application of substrates was expanded.The synthesized new target compounds were not reported in the literature,and¹HNMR,¹³CNMR,IR,MS and single crystal diffraction were used for structural confirmation.After synthesizing a series of dienone derivatives,explore the synthesis of new pyrrolopyrimi Dine skeleton compounds and design4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidine-ketone.The structure of 6-ketone was modified,a chlorine-containing group was introduced on the heterocyclic ring containing two nitrogens,and a benzyl group was introduced on the nitrogen atom of the pyrrole ring,which expanded the application range of pyrrolopyrimidine skeleton compounds and adopted a series of methods to synthesize 7-benzyl-2,4-dichloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ketone,and to characterize its structure.（1E,4E）-1,5-diarylpentan-1,4-diene-3-ketone for Michael addition,the conditions used are4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]-ketone.The reaction conditions of pyrimidin-6-one and dienone finally obtained a new spirocyclic pyrrolopyrimidine compound with a yield of 90%.Thus,a new class of spirocyclic pyrrolopyrimidine compounds was synthesized.