Palladium‐Catalysed Amination of Electron‐Deficient or Relatively Electron‐Rich Benzo[<i>b</i>]thienyl Bromides − Preliminary Studies of Antimicrobial Activity and SARs

Abstract

Abstract Several diarylamines in the benzo[ b ]thiophene series were prepared in good to high yields by palladium‐catalysed amination of ethyl 3‐bromobenzo[ b ]thiophene‐2‐carboxylate with anilines and 5‐aminoindole in the presence of Pd(OAc) 2 , BINAP and Cs 2 CO 3 in toluene. The presence of the ester group at the 2‐position of the benzo[ b ]thiophene moiety increases the yields and lowers the heating times relative to the reactions performed with 3‐bromobenzo[ b ]thiophene. When aminopyridines were used instead of anilines, the ligand and the solvent need to be changed to XANTHPHOS and dioxane in the amination reaction. With 2‐aminopyridine a one‐pot C−N coupling and intramolecular cyclization involving the nitrogen atom of the pyridine ring occurred, with loss of ethanol, giving an interesting fluorescent tetracyclic heteroaromatic compound. The antimicrobial activity, the minimal inhibitory concentrations (MICs) and the structure‐activity relationships (SARs) were evaluated. A selectivity with low MICs was observed against Bacillus Cereus , and good results were also obtained against Candida albicans . The acids obtained by hydrolysis of the ester group, as non‐proteinogenic α,β‐unsaturated β‐amino acids, can be incorporated into peptide chains to induce conformational constraints. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)