Sodium hydride → N-Benzyl-2-hydroxy-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carboxamide hydrochloride

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Reaction Steps

Sodium hydride (0.033 g of 60% dispersion in paraffin, 0.84 mmol) was washed with hexane, dried in vacuo and suspended in N,N-dimethylformamide (1 mL). N-Benzyl-2-oxoindoline-5-carboxamide (0.110 g, 0.41 mmol) and 1-[(6-chloropyridin-3-yl)sulfonyl]-4-methylpiperazine (0.170 g, 0.62 mmol; described in: Thunus L. Annuale Pharmacetiques Francisies, 1977, 35, 197-203) were dissolved in N,N-dimethylformamide (5 mL) and added to the suspension of sodium hydride. The reaction mixture was stirred at room temperature for 10 min and subsequently heated for 1 h at 90° C. After cooling to room temperature, a saturated aqueous sodium hydrogen carbonate solution was added (4 mL). Silica gel (8 mL) was added and the solvent was removed in vacuo. The residue was purified on a silica gel column using a gradient of chloroform/methanol mixtures, (40:1 to 1:1 and 2% triethylamine), as the eluent. The base was dissolved in a mixture of chloroform (5 mL) and methanol (5 mL). Hydrogen chloride (3 mL, 1 M in diethyl ether) was added and stirring was continued for 10 min. The precipitate was washed with diethyl ether and dried in vacuo at 60° C. to give 0.035 g (16% yield) of the title compound: 1H NMR (D2O, 400 MHz) δ 7.79 (m, 1H), 7.42 (m, 4H), 7.37 (m, 1H), 7.24 (m, 1H), 7.14 (m, 2H), 6.80 (m, 1H), 6.68 (m, 1H), 4.50 (s, 2H), 3.77 (m, 2H), 3.60 (m, 2H), 3.22 (m, 2H), 2.91 (m, 5H); MS (ES) m/z 506 (M++1).

Provenance & Evidence