Divergent Protocol for the Synthesis of Isoquinolino[1,2-b]quinazolinone and Isoquinolino[2,1-a]quinazolinone Derivatives

The development of robust and step-economic strategies to access structurally diverse drug-like compound collections remains a challenge. A distinct structural option that constitutes the core scaffold of many biologically significant molecules is the quinazolinone ring system. Several members of this family of privileged substructures have gained attention due to their diverse biological activities. In this context, the development of an efficient strategy for their access is needed. Herein, we report a divergent metal-free operation to access a diverse collection of C6-substituted pyrrolo [4 ',3 ',2 ':4,5 ] is oquinolino [1,2-b ] quinazolin-8 ( 6H)-one and pyrrolo [4 ',3 ',2 ':4,5 ] is oquinolino [2,1-a]-quinazolin-12(6H)-one architectures. The described cascade unites Friedel-Crafts and aza-Michael addition reactions. This operationally simple protocol enables a rapid access to these scaffolds and is compatible with a wide scope of starting materials. In addition, the cascade features a promising approach for the design of unique compound libraries for drug design and discovery programs.

Automated summary

The development of robust and step-economic strategies to access structurally diverse drug-like compound collections, specifically quinazolinone ring system, is still a challenge. To address this, a metal-free operation using Friedel-Crafts and aza-Michael addition reactions is reported, enabling rapid access to C6-substituted pyrroloquinazolinone and pyrroloquinazolinone architectures. This operationally simple protocol is compatible with a wide range of starting materials and offers a promising approach for the design of compound libraries for drug design and discovery programs.