Solid Phase Synthesis Of Heterocyclic Compounds From Resin-bound Acylhydrazine Reagent

This thesis focuses on the solid phase synthesis of several kinds of heterocyclic compounds from the resin-bound acylhydrazine.The following are the main parts studied in detail:Firstly,the resin-bound acylhydrazine reagent was directly applied in solid phase organic synthesis of heterocyclic compounds:1.Dinucleophilic site exists in acylhydrazine,which can undergo tandem reaction with kinds of dielectrophilic reagents.We applied resin-bound acylhydrazine into solid phase organic synthesis of adenosine acceptor inhibitors,and got the pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidines derivatives in good yields and high purities.2.The resin-bound acylhydrazine was reacted with isocyanates to afford the aroylsemicarbazide resin.Then,the intramolecular cyclization of the resin was carried out in the presence of NaOH(aq.),providing the 1,2,4-triazol-3-one resin after acidified by HCl(aq.).After cleavaged by TFA/DCM,we got the desired compounds.3.Reaction of acylhydrazines resin with ketone afforded the corresponding support-bound acylhydrazones.After Hurd-Mori type cleavage accomplished using thionyl chloride,many kinds of 1,2,3-thiadiazoles derivatives were efficiently obtained in good yield and high purity via traceless cyclization cleavage of resin-bound acylhydrazones.Secondly,a novel resin-bound 4-amino-5-mercapto-1,2,4-triazole was prepared from acylhydrazines resin in optimal method.The facile and potent methods for solid phase synthesis of related fuse heterocyclic compounds were provided based on this resin. 1.The resin was reacted with halogenated ketone to afford the 1,2,4-triazolo-[3, 4-b]-[1,3,4]thiadiazine derivatives.2.Solid phase synthesis of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were completed by the reaction of this resin with carboxylic acid.The reaction conditions presented in this thesis were mild,and the desired products were efficiently obtained in good yield and high purity.This approach could be used to design and synthesize the diversity-oriented small molecule library in combinatorial chemistry.