ABSTRACT In this paper, we developed a straightforward protocol for catalyst‐free (3 + 2) cycloaddition between quinazoline‐derived azomethine imines and arylidene pyrazolones to provide a series of spiropyrazolone‐fused pyrazolo1,5‐ c quinazolines with yields ranging from moderate to good. These products possess three contiguous stereocenters, including a quaternary carbon center, and exhibit excellent regio‐ and diastereoselectivity (up to > 25:1 dr). Moreover, this approach entails the utilization of readily accessible starting materials, encompasses a wide range of substrates, operates under mild reaction conditions, and offers the advantages of simple operational procedures and 100% atom economy. Additionally, the novel privileged structures incorporating spiropyrazolone and pyrazolo1,5‐ c quinazoline motifs demonstrate potential to be MEP1B inhibitors through a molecular docking study. The structural framework and relative configuration of the representative product were conclusively determined through single‐crystal x‐ray diffraction analysis.
Wang et al. (Tue,) studied this question.