Synthesis Of Isoquinolinotriazole And Pyridopyrazine

Isoquinolinotriazole is an important organic compound.The related derivatives not only show some important pharmacological activities,but also have important applications in fluorescent materials and organic synthesis.In this paper,isoquinolinotriazole was synthesized by using a unique triazole and tetra-n-butylammonium fluoride(TBAF)as additive.The process contains Ts removing and intramolecularly cyclization.The optimal reaction conditions were TBAF(0.6 equiv,1 M in THF),toluene as solvent,100 ℃,10 min.In the process of substrate expansion,most of the products can obtain almost equivalent yield under mild conditions.When the reaction conditions are changed a little,the halogen substituted isoquinolinotriazole with great application value can be synthesized.The substitution of halogenated compounds by NBS and NIS is not the same,which shows the application value of this method.In the study of derivatization of isoquinolinotriazole,functional isoquinoline can be obtained by adding Bronsted acid,Rhodium and Copper to promote the denitrogenation of triazole.Through the control experiment,we verified that the trace water contained in the commercial TBAF reagent also participated in the reaction process,and finally confirmed that the reaction mechanism was that the final product was obtained through the removal of Ts protective group first,and then the nucleophilic addition reaction of carbon-carbon triple bond.In addition,pyridopyrazine skeleton exists in many natural products and drug molecules with important physiological activities.In this paper,4-oxo-substituted N-sulfonyl-1,2,3-triazoles and pyridine sulfur salts were used to synthesize various functional group substituted pyridinopyrazines without other additives.The optimal reaction conditions were:4-oxo-substituted N-sulfonyl-1,2,3-triazole(0.4 mmol),pyridine sulfide(0.2 mmol),ethylene glycol dimethyl ether as solvent,80 ℃,0.5–3 h.Through the extended study of the reaction substrate,the reaction showed good compatibility with a variety of functional groups,and the reaction yield was medium to good.Through the analysis of the reaction mechanism,this reaction involves a rare intramolecular addition elimination process in the reaction of pyridine sulfur salt,and finally produces a pyridopyrazine compound containing an exothione ester.In addition,the derivatization of the reaction products is in progress.