Hydrochloric Acid → 861238-35-9

Participants

Reaction Steps

To a solution of (E)-3-[1-(2,4-dichloro-benzyl)-5-fluoro-3-methyl-1H-indol-7-yl]-acrylic acid (10.0 g, 26.4 mmol) in dichloromethane (100 mL) was added EDCI (7.9 g, 41.2 mmol), HOBt hydrate (0.71 g, 5.3 mmol), and diisopropylethylamine (10.6 g, 81.8 mmol), and the mixture was stirred for 20 mm. To the reaction was added 4,5-dichlorothiophene-2-sulfonamide (6.43 g, 27.2 mmol), and the mixture was stirred at room temperature for 15 mm, then at reflux for 16 h. The reaction was cooled to room temperature then diluted with 25 mL water followed by 25 mL 2 M HCl. The mixture was stirred for 5 mm, then the phases were split. The organic phase was diluted with 25 mL of 2 M HCl and stirred, which induced precipitation of the product. The temperature was reduced to 0° C., and stirring was continued for 1 h. The product was collected via vacuum filtration, washed with water (3×25 mL) and heptanes (2×25 mL), then vacuum dried at 60° C. to afford 9.3 g (60% yield) of the title compound. The product could be further purified via recrystallization from ethanol: 1H-NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 5.53 (s, 2H), 6.12 (d, 1H, J=8.4 Hz), 6.21 (d, 1H, J=15.4 Hz), 7.04 (dd, 1H, J=10.0, 2.4 Hz), 7.22 (dd, 1H, J=8.4, 2.0 Hz), 7.37 (s, 1H), 7.38 (d, 1H, J=2.0 Hz), 7.46 (dd, 1H, J=9.2, 2.4 Hz), 7.74 (d, 1H, J=15.4 Hz), 7.90 (s, 1H).

Provenance & Evidence