Copper-Catalyzed Synthesis Of Nitrogen Heterocyclic Compound

Indole and quinazoline derivatives are two kinds of important nitrogen-containing heterocyclic compounds, The cores of them are privileged structural motifs found in both designed medicinal agents and in natural products. Nevertheless the classical synthetic methods of these compounds has some disadvantages. For example, the used starting materials often are not readily available and difficult to prepare, inefficient, and so on. Therefore, based on the development of efficient synthetic methods is very necessary. Based on the copper-catalyzed Ullmann coupling reactions, we developed two new kinds of synthetic methods of these compounds.1:A simple and efficient copper-catalyzed method was developed for the synthesis of 2-amino-lH-indole-3-carboxylate derivatives via cascade reactions of substituted N-(2-halophenyl)-2,2,2-trifluoroacetamide with alkyl 2-cyanoacetate or malononitrile under mild conditions, and the method is of wide practical application. The protocol uses 10 mol% CuI as catalysts,20 mol%L-proline as the ligand, K2CO3 as base and DMSO:H2O(1:1) as solvent. The corresponding indole derivatives containing amino and carboxylate groups were obtained in good yields. And they are biologically active molecules and important intermediates for the construction of medicinal molecules. It will provide an opportunity for the construction of useful molecules.2:An efficient copper-catalyzed method was developed for synthesis of 4-aminoquinazoline and 2,4-diaminoquinazoline derivatives via reactions of substituted 2-bromobenzonitriles with amidines or guanidine. The protocol uses 10 mol% CuI as catalyst,20 mol %DMEDA as ligand and DMF as solvent. And the method is of economical and practical advantages. It will provide an opportunity for the construction of diverse and useful molecules in organic chemistry and medicinal chemistry.