Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• for a practical synthesis of vernakalant. Keywords: APS-DMSO; imides; practical synthesis; radical-mediated; vernakalant; Introduction Cyclic imides are privileged pharmacophores and important building blocks for the synthesis of natural products, drugs, agrochemicals, advanced materials and

• elegant transformation (Tables 2–4), we planned to explore our imide forming protocol to the synthesis of the drug vernakalant (11). It was discovered by Cardiome/Astellas Pharma Inc. and later developed as a novel antiarrhythmic agent for the treatment of atrial fibrillation (cardiac arrhythmia leading

• to strokes) in collaboration with Merck & Co., Inc. Its intravenous formulation has been approved as a drug by the European agency (EMEA) under the trade name Brinavess (Cardiome/Merck) [64]. Few synthetic routes to vernakalant (11) and its intermediates have been reported in the literature [64]. Our