ORGN 221 |
| Sulfonamides are currently used as therapeutic agents. Several solid-phase routes have been reported for the synthesis of sulfonamides. Unfortunately, for the synthesis of sulfonamides, polymer-bound reagents attached to safety-catch linkers have not been developed extensively. Two novel safety-catch linkers were synthesized by reaction between 4-(5¢-formyl-2¢-hydroxyphenyl)benzoic acid (1a) and 4-(5¢-formyl-2¢-hydroxyphenyl)phenyl propionic acid (1b), respectively, with aminomethyl polystyrene resin (2) in the presence of 1-hydroxybenzotriazole and 1,3-diisopropylcarbodiimide to afford 3. The phenolic hydroxyl group in 3 was acetylated by acetic anhydride. The reductive amination of a polymer-bound aldehyde 4 by amines (e.g., 4-chloroaniline, benzyl amine, 4-methoxybenzyl amine, aniline, 4-chloroaniline) and sodium triacetoxyborohydride gave 5. Sulfonylation of resin-bound amine 5 with alkyl or arylsulfonyl chloride derivatives in the presence of base afforded the polymer-bound sulfonamides 6. The cleavage of resin 6 in TFA/DCM produced the desired pure sulfonamides (7, overall yield ~80-85%).
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Asymmetric Reactions and Syntheses, Metal-Mediated Reactions, Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Organic Chemistry |
