Dimethylformamide → N-[3-(2-chlorophenyl)-1-(piperidin-1-ylcarbonyl)propyl]-1H-indole-4-sulfonamide

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Reaction Steps

A solution of 1.1 g (3.4 mmol) of methyl 2-[(tert-butoxycarbonyl)amino]-4-(2-chlorophenyl)butanoate in 8 mL of 1:1 CH2Cl2/TFA is stirred for 1 h. The mixture is concentrated and 10 mL of DMF, 1.5 mL (8.5 mmol) of iPr2NEt, and 0.81 g (3.7 mmol) of indole-4-sulfonyl chloride are added. The mixture is stirred for 12 h, diluted with water, and extracted with EtOAc. The extract is washed with brine, dried over MgSO4, filtered and concentrated. The residue is purified by flash chromatography (0-100% EtOAc in hexanes) to provide 1.0 g (73%) of the sulfonamide. This material (0.48 g, 1.2 mmol) is then dissolved in 5 mL of dioxane and 2.9 mL (2.9 mmol) of 1 M NaOH. After starting material is consumed, the mixture is concentrated, redissolved in water, and extracted with CH2Cl2. The extract is discarded, and the pH of the aqueous solution is adjusted to 3 with 1 N HCl. The mixture is extracted with CH2Cl2/DMF. The extract is concentrated to provide 0.39 g (86%) of the acid 4-(2-chlorophenyl)-2-[(1H-indol-4-ylsulfonyl)amino]butanoic acid.

Provenance & Evidence