The first examples of amino acid derived α,β-unsaturated esters to Z-alkylidene oxindoles via 3-aza-Cope rearrangement using In(OTf) are reported.

No abstract

Nintedanib, a potent, oral, small‐molecule tyrosine kinase inhibitor, is known as a triple angiokinase inhibitor, inhibiting three major signaling pathways in angiogenesis. Here, we report full details of the alternative path toward the synthesis of nintedanib via novel intermediates. A key feature of our approach is the stereoselective intramolecular cyclization strategy that enables the concise conversion of β‐keto amide into a 3‐acyloxindole derivative, which is an important scaffold for nintedanib synthesis. Subsequent condensation of oxindole scaffold with synthesized amine derivative led to the drug nintedanib with good yields.