A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

Summary A series of functionalized benzimidazo[1,2-c]quinazoline derivatives was obtained in excellent yields under mild conditions through a CuI-catalyzed Ullmann N-arylation starting from easily available starting materials.


Introduction
Nitrogen-containing heterocycles are ubiquitous backbones in natural products, medicine and organic materials. In addition, they are also important ligands for catalytic reactions. Recently, the conjugation of different types of azaheterocycles in the same molecule has received considerable attention since the resulting ring-fused molecules often show unique organic optoelectronic properties and bioactive activities [1,2]. Among them, benzimidazo [1,2-c]quinazolines were intensively investigated and promising biological activities were observed, such as anticancer, antiviral, antimicrobial, anti-inflammatory and anticonvulsant [3][4][5]. Indeed, some of them are already used as antimicrobial agents and lipid peroxidation inhibitors [6].
reaction and provided the corresponding quinazolines 4 in high yields (Table 2, entries 2, 3 and 6). In addition changing the position of the fluoro substituent did not affect the yield of the products ( Table 2, entries 3-5).
To further expand the scope of the protocol, we attempted the synthesis of imine 3g starting from two different nitriles. The reaction of o-cyanoaniline (1a), benzonitrile (1g) and di-(obromophenyl)iodonium salt 2 in the presence of Cu(OTf) 2 gave the desired imine 3g together with imine 3a. After isolation of 3g it was further treated with 10 mol % of CuI in DMSO for 50 min to give product 4g in quantitative yield (Scheme 2).
It is worth mentioning that during the course of our study, we observed that products 4 were not stable to acid. For example, treatment of 4c with aqueous HCl solution led to ring-opening product 5 (Scheme 3). The structure of 5 was confirmed by X-ray diffraction analysis (Figure 1

Supporting Information
Supporting Information File 1 Full experimental procedures, characterization data, and NMR charts for compounds 3a-g and 4a-g.