Scheme 3. Preparation of Sulfonimide Derivatives of 2′-Des-methyl Sulindac Sulfide.
Syntheses were performed on a parallel synthesis apparatus using a straightforward one-pot, two-step CDI carbodiimide coupling reaction (route A).67 Alternatively, the two-step sulfonamide couplings could be accomplished with oxalyl chloride as the carboxylic acid activator, according to a disclosed procedure, as established for compound 21c (route B).65,86,87 Reagents and conditions: (Route A): (a1) CDI/DCM, 0–5 °C, 2 h; (b1) alkyl-/arylsulfonamide, DBU, RT, overnight. (Route B): (a2) oxalyl chloride/DCM, RT, overnight; (b2) alkyl-/arylsulfonamide, 1,2-DCE, pyridine, RT, overnight.