One‐Pot, Three‐Component Sulfonimidamide Synthesis Exploiting the Sulfinylamine Reagent N‐Sulfinyltritylamine, TrNSO

• Published in: Angewandte Chemie International Edition 2017-11, Vol.56 (47), p.14937-14941
• Main Authors: Davies, Thomas Q., Hall, Adrian, Willis, Michael C.
• Format: Article
• Language: English
• Subjects: Amines; Celecoxib; Chemical synthesis; COX-2 inhibitors; Cyclooxygenase-2; Indoles; medicinal chemistry; one-pot synthesis; Pyridines; Reagents; sulfinylamines; sulfonimidamides; sulfur functional groups; Thiols
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201708590

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. Come and join us: The stable, readily prepared sulfinylamine reagent TrNSO is exploited as a linchpin to join organometallic reagents and amines to provide sulfonimidamides in a high yielding one‐pot process. Good variation of both reaction components is possible.