Dimethyl Sulfoxide → 2-Chloro-4-((2-furylmethyl)amino)-5-((4-(nitrooxy)piperidyl)carbonyl)benzenesulfonamide

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Reaction Steps

To a mixture of furosemide (331 mg, 1 mmol) and nitrooxy-4-piperidyl, nitric acid salt (prepared as described in U.S. application Ser. No. 60/505,921, Example 16a) (209 mg, 1 mmol) in ethyl acetate (25 mL) and methylsulfoxide (10 mL) was added triethyl amine (0.125 mL) and the reaction mixture was stirred at room temperature for 10 minutes. To the resulting mixture were added successively EDAC (0.192 g, 1 mmol) followed by DMAP (0.122 g, 1 mmol). The resulting solution was then stirred under nitrogen atmosphere at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water, aqueous NaHCO3, water, brine, dried over sodium sulfate, filtered, and the organic extracts were evaporated. The product was purified by column chromatography over silica gel using 5% methanol in dichloromethane to give the title compound (390 mg, 85% yield) as colorless thick oil. 1H NMR (CDCl3) δ 7.74(s, 1H), 7.47 (s, 1H), 6.83 (s, 1 H), 6.25-6.15 (m, 3H), 5.31 (s, 2H), 5.18 (m, 1H), 4.34 (d, J=5.2 Hz, 2H), 3.74-3.64 (m, 2 H), 3.53-3.52 (m, 2H), 2.02 (m, 2H), 1.79 (m, 2H); LRMS (APIMS) m/z 459 (MH+), 441 (M−H2O).

Provenance & Evidence