New Synthesis of Nintedanib, its Key Starting Materials and Key Synthetic Intermediates and their uses thereof

• Robust and scalable process for large-scale synthesis
• Simple 2–4 step convergent approach using tandem/domino reactions
• Fewer reagents, with improved yield (CDRI: 35–51% vs. known: 30–35%)

• A simple, scalable, and stereoselective Pd-catalyzed Heck/Buchwald–Hartwig cascade enables efficient synthesis of 3-(aminoalkylidene)oxindoles with broad functional group tolerance.
• Developed an efficient multigram synthesis of nintedanib (99% HPLC purity) using commercially available materials via two synthetic routes.
• The process uses optimized conditions, avoids column chromatography and hazardous Pd/C hydrogenation steps found in earlier methods.

• Uses eco-friendly solvents like toluene and dioxane
• Cost-effective and mild reaction conditions
• No column chromatography needed