Study On Pd-catalyzed Arylation And Regioselective Cyanation Reaction Of Diaza-aromatic

In this thesis,Pd-catalyzed Suzuki cross-coupling reaction of 3-bromo-1H-indazol-5-amine with(hetero)arylboronic acids under microwave-assisted has been developed.The novel Pd-catalyzed decarboxylative cross-coupling reaction of pyridazine-3-carboxylic acids with aryl and heteroaryl-bromides for C-C bond formation has been successfully achieved.A series of 4-and 5-aryl/heteroarylpyrimindines derivatives was synthesised via Pd-catalyzed decarboxylative cross-coupling reaction of pyrimidinecarboxylate with aryl and heteroaryl-bromides.A general and reliable method for the synthesis of 5-substituted-3-pyridazine carbonitrile from 4-substituted pyridazine through a regioselective Reissert-type reaction was activated.1.Pd-Catalyzed Suzuki Cross-Coupling Reactions of 3-Bromo-1H-indazol-5-amine With Aryl(hetero)Boronic Acid Under Microwave-assistedHerein,a simple and efficient protocol to various 3-aryl-1H-indazol-5-amine derivatives through Pd-catalyzed Suzuki-Miyaura cross-coupling reaction of(NH)free 3-bromo-indazol-5-amine with arylboronic acids under microwave-assisted has been developed.The coupling reaction can be carried out under the conditions with dioxane/H2 O as solvent,5 mol % Pd(OAc)2 as catalyst,10 mol % Ru Phos as ligand and K3PO4 as base in good to excellent yields.The reaction system is applicable to a wide range of substrates and with high functional group tolerance(Scheme 1).Scheme 1 Pd-catalyzed suzuki cross-coupling reactions of 3-bromo-1H-indazol-5-amine 2.Arylation of Pyridazine via Pd-Catalyzed Decarboxylative Cross-Coupling Reactions of Pyridazine-3-carboxylic AcidA novel synthetic route to 3-aryl-and heteroaryl-pyridazines was discovered and developed via the Pd-catalyzed decarboxylative cross-coupling reaction of stable pyridazine-3-carboxylic acid with aryl-and heteroaryl-bromides using 5 mol % Pd(PPh3)4 as catalyst,1.0 equiv Cu2 O as additives,Li2CO3 as base,DMA as solvent.In addition,the substituted pyridazine-3-carboxylic acids was also suitable for this reaction.The method has broad functional group compatibility(such as alkyl,cyano,ester,ether,halide,ketones and aldehyde et al.)(Scheme 2).Scheme 2 Decarboxylative cross-coupling reactions of pyridazine-3-carboxylic acid3.Arylation of pyrimidines via Pd-Catalyzed Decarboxylative Cross-Coupling Reactions of Pyrimidine CarboxylateA novel method has been developed for the preparation of 4-aryl-and heteroaryl-pyrimidine through the Pd-catalyzed decarboxylative cross-coupling reactions of pyrimidine-4-carboxylate with aryl-and heteroaryl-bromides.The cross-coupling reactions is also efficient to the pyrimidine-5-carboxylate by using 5 mol % Pd(PPh3)4 as catalyst,0.5 equiv Cu2 O as additives,DMA as solvent.Moreover,a wide range of substituted aryl-and heteroaryl-bromides can fit this system as well,The notable advantage of the protocol is simple and good functional group tolerance(Scheme 3).Scheme 3 Decarboxylative Cross-Coupling Reactions of Pyrimidine Carboxylate4.Preparation of 5-Substituted-3-pyridazine Carbonitrile via Regioselective Reissert-type reactionA facile and efficient protocol for one-pot two-step synthesis of 5-substituted-3-pyridazine carbonitrile derivatives via regionselective Reissert-type reaction has been developed.This methodology provides a novelty route to 5-substituted-3-pyridazine carbonitrile by employing 4-substituted pyridazine as material,TMSCN as cyanating reagent,Ts Cl as acylation reagent,Al Cl3 as catalyst,DBU as base and THF as solvent.The corresponding products were obtained in good selectivity(Scheme 4).Scheme 4 Synthesis of 5-substituted-3-pyridazine carbonitrile...