DYNO‐MILL‐Assisted Mechanochemistry: Design of Experiments Optimization for Sustainable Synthesis of Pyrrolo[3,4‐ c ]pyrazoles

We report a sustainable DYNO-MILL-assisted mechanochemical synthesis of pyrrolo[3,4-c]pyrazoles via (3 + 2) cycloaddition between in situ generated nitrile imines and maleimides. Design of experiments (DoE) optimization identified key milling parameters, enabling efficient product formation in up to 78% yield under solvent-minimized, catalyst-free conditions. The method provides broad substrate scope, operational simplicity, and scalability. Comparative green metrics analysis highlights reduced waste generation and improved sustainability relative to conventional solution-phase approaches.