One-pot, three-component sulfonimidamide synthesis exploiting the sulfinylamine reagent N -sulfinyltritylamine, TrNSO

Journal article

Sulfonimidamides are increasingly important molecules in medicinal chemistry and agrochemistry, but their preparation requires lengthy synthetic sequences, which has likely limited their use. We describe a one-pot de novo synthesis of sulfonimidamides from widely available organometallic reagents and amines. This convenient and efficient process uses a stable sulfinylamine reagent, N-sulfinyltritylamine (TrNSO), available in one step on 10 gram scale, as a linchpin. In contrast to classical approaches starting from thiols or their derivatives, our TrNSO-based approach facilitates the rapid assembly of the three reaction components into a variety of differentially substituted sulfonimidamides containing medicinally relevant moieties, including pyridines and indoles. Analogues of the sulfonamide-containing COX-2 inhibitor Celecoxib were prepared and evaluated.

Authors: Davies, T; Hall, A; Willis, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Angewandte Chemie
• Volume: 129
• Issue: 47
• Pages: 15133-15137
• Publication date: 2017-09-19
• DOI: 10.1002/ange.201708590
• EISSN: 1521-3757
• ISSN: 0044-8249
• Keywords: medicinal chemistry; one-pot synthesis; sulfinylamines; sulfonimidamides; sulfur functional groups