Synthesis Of 5,12 - Dihydroindolo [2,1 - B] Quinazoline Derivatives By Copper

The1,2,3,4-tetrahydropyrimido[1,2-a]indole and indolo[2,1-b]quinazoline skeletons exist in the core structures of several biologically active compounds. The known methods for synthesis of1,2,3,4-tetrahydro pyrimido[1,2-a]indole and indolo[2,1-b]quinazoline have suffered from limitations such as limited availability of starting materials, harsh reaction conditions, and poor overall yield of multi-step synthesis. It is highly desirable to develop an efficient synthetic method and expand the structure diversity for current medicinal chemistry needs.Over the past years, copper-catalyzed coupling reactions in C-C, C-heteroatom bond formation have achieved remarkable progress, especially, copper-catalyzed Ullmann-Type domino synthesis of heterocycles have become one of the hot research topics. The purpose of this thesis is to construct new types of heterocycles via copper-catalyzed Ullmann-Type domino coupling reactions.5,12-Dihydroindolo[2,1-b]quinazoline derivatives was selected as target molecules. N-(2-Bromobenzyl)-2-halogenaniline and activated methylene compounds were used as starting materials. A comprehensive study on the copper-catalyzed domino Ullmann-Type intermolecular C-C and intramolecular C-N coupling was carried out and a catalyst system using Cul as catalyst,rrans-4-OH-L-proline as ligand, DMSO as solvent was established. By heating in a sealed tube under argon atomosphere, the target products were obtained in good yields. Such a method is easily manipulated with relatively wide substance scopes. Mechanistic studies of the cascade reactions were also pursued, possible reaction mechanism was proposed. It’s nothworthy that in the cascade coupling reactions, nonactivated substrates were adoped. The copper-catalyzed Ullmann-Type reaction on nonactivated system was reported only in a few publications. The main research results were published on Org. Lett.