Synthesis of (Indol-3-yl)methanesulfonamide and its 5-Methoxy Derivative

Abstract

Two methods for the synthesis of (indol-3-yl)methanesulfonamide were elaborated based on the 'switching off' the reactivity of the indole nucleus in the intermediates by using indoline or indoxyl compounds. (2,3-Dihydroindol-3-yl)methanesulfonic acid was the key compound used in the indole-indoline approach and (1-acetyl-3-hydroxy-2,3-dihydroindol-3-yl)-N-(tert-butyl)methanesulfonamide was the key intermediate when 1-acetylindoxyl was used as the starting compound. (1-Acetyl-3-hydroxy-2,3-dihydroindol-3-yl)-N-(tert-butyl)methanesulfonamide (15)A 2.5 M solution of BuLi (17 mL, 43 mmol) was slowly added to a stirred solution of i-Pr 2 NH (6.5 mL, 46 mmol) in anhyd THF (40 mL) at -78 °C in a stream of argon. The mixture was slowly warmed up to 0 °C and then cooled again to -78 °C. A solution of N-(tertbutyl)methanesulfonamide (14; 3.0 g, 20 mmol ) in THF (20 mL) was added at this temperature under stirring. Then the reaction mixture was slowly warmed up to -30 °C and stirred at this temperature for 30 min, cooled again to -78 °C and at this temperature a solution of 1-acetylindoxyl (13; 3.5 g, 20 mmol) in anhyd THF (50 mL) was quickly added. The mixture was stirred at -78 °C for 30 min, then warmed to 0 °C and poured into a water/ice/concd HCl mixture (300 mL:200 g:20 mL). The product was extracted with EtOAc, the extract was washed with H 2 O, dried, and evaporated. The residue was purified by column chromatography in CHCl 3 -MeOH (9:1). Compound 15 (0.3 g, 5%) was isolated as colorless crystals; mp 192-193°C; R f 0.52 (CHCl 3 -MeOH, 9: 1). 1 H NMR (CDCl 3 ): δ = 8.16 (d, 1 H, J = 7.

Synthesis and Biological Evaluation of Chalconesulfonamides: En Route to Proapoptotic Agents with Antiestrogenic Potency

“…The generation of nucleophilic reagents by ionization of C-H and N-H groups is a common method in organic synthesis. Metalation of methanesulfonamide derivatives allows for the synthesis of aliphatic sulfonamides with complex structures that are difficult to obtain with other methods [ 26 , 27 , 28 ]. Therefore, we use the metalation of methanesulfonamide as a useful approach to obtain the key intermediate 6 for the synthesis of the target compound 7 .…”