Ru-catalyzed C-H annulation: accessing quinazolinone-BCP hybrids from stable precursors.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Catalysis

Background:

• Quinazolinones are privileged scaffolds in medicinal chemistry.
• Bicyclo[1.1.1]pentanes (BCPs) are valuable building blocks for drug discovery.
• Efficient methods for combining these motifs are needed.

Purpose of the Study:

• To develop a novel synthetic route to quinazolinone-BCP hybrids.
• To explore the utility of ruthenium-catalyzed C-H annulation for this purpose.
• To enable late-stage functionalization and diversification of drug-like molecules.

Main Methods:

• Ruthenium-catalyzed C-H annulation reaction.
• Utilized benzimidates and bench-stable BCP-dioxazolone reagents.
• Optimized reaction conditions for efficiency and scalability.

Main Results:

• Achieved efficient synthesis of quinazolinone-BCP hybrids.
• Demonstrated broad substrate scope and mild reaction conditions.
• Confirmed scalability of the developed synthetic strategy.

Conclusions:

• The developed ruthenium-catalyzed annulation is a powerful tool for synthesizing quinazolinone-BCP hybrids.
• This strategy facilitates structural diversification of drug-like molecules.
• The method is suitable for late-stage functionalization in drug discovery programs.