Convenient procedure for the preparation of alkyl and aryl substituted N-(aminoalkylacyl)sulfonamides

✍ Scribed by James T. Drummond; Graham Johnson

• Publisher: Elsevier Science
• Year: 1988
• Tongue: French
• Weight: 210 KB
• Volume: 29
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)82009-2

✦ Synopsis

A convenient synthesis of N-(aminoalkylacyl)sulfonamides from CBZ potected glycine, B-alanine and GABA is described. During an investigation into the preparation of new pharmacologically active amino acid analogs we wished to explore the pharmacological properties of compounds which bore both an equiionizable carboxylic acid isostere and lipophilic substituents at this new acidic terminus. It appeared to us that one functionality which provided this combination of features was the N-acylsulfonamide group. Accordingly, we targeted the synthesis of a series of N-(aminoalkylacyl)sulfonamides. Investigation of the literature for routes by which to prepare these potentially useful compounds revealed a number of alternate procedures1'2'3'*. However, from our requirements of generality, ease of synthesis and the need to prepare a range of derivatives in amounts sufficient for pharmacological evaluation, these reported procedures were inadequate to our needs. Consequently, we sought to develop a simple and efficient route by which to prepare these novel structures. We wish to report here an effective route for the preparation of alkyl and arylsulfonyl substituted amino acid amides. Initially, we investigated the reaction of toluenesulfonamide with carbonyldiimidazole activated t-BOC protected glycine (Scheme). Following prolonged reflux, this procedure gave cleanly but rather slowly the desired N-acylsulfonamide (19) as a crystalline solid (Table ). Removal of the t-BOC group was achieved using standard trifluroacetic acid treatment.