Affiliation:
1. Chemistry Process R&D Idorsia Pharmaceuticals Ltd. CH-4123 Allschwil Switzerland
2. Drug Discovery Chemistry Idorsia Pharmaceuticals Ltd. CH-4123 Allschwil Switzerland
Abstract
AbstractOxindoles are prevalent structures in natural products and pharmaceutically active molecules. To support structure–activity‐relationship (SAR) studies in a medicinal chemistry program, we developed a straightforward and scalable synthesis route to 1‐aminoethyl oxindole building blocks harboring various types of substituents. Our strategy relies on an intramolecular Buchwald–Hartwig amidation of a 2‐bromophenylacetic amide precursor. The cyclization substrates can be prepared from readily available benzaldehydes by ortho‐selective C(sp2)−H bromination followed by homologation to the corresponding phenylacetic acid derivatives. The process was optimized to allow for preparation of 246 g of one representative example.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Drug Discovery,Biochemistry,Catalysis