Tetrahydrofuran → HCID 57585129, compound

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Reaction Steps

To a 50 ml round-bottom flask equipped with a stir bar, was added 5-bromo-2-chloropyridin-3-amine (0.250 g, 1 mmol) while under inert atmosphere. The solid was dissolved in THF (10 ml, 122 mmol), then sodium bis(trimethylsilyl)amide (0.650 g, 3 mmol) was added to the mixture and allowed to stir 5 minutes. Then cyclohexanesulfonyl chloride (0.5 ml, 4 mmol) was added into the mixture. The mixture was allowed to stir overnight, while under inert atmosphere. The progress of the reaction was monitored by LC/MS, which showed product and a small amount of bis-sulfone material in the mixture. The mixture was diluted with DCM and water. The organic layer was extracted with DCM (3×25 ml). Combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was dissolved in methanol (5 ml), then potassium carbonate (0.250 g) was added to the mixture with stirring. After 20 minutes, the progress of the de-sulfonylation reaction was monitored by LC/MS, which showed mostly desired product. The mixture was filtered and concentrated in vacuo. The crude was purified by ISCO silica-gel chromatography, in a gradient of 1-15% ethyl acetate/hexanes. This gave N-(5-bromo-2-chloropyridin-3-yl)cyclohexanesulfonamide (0.140 g, 33% yield) as an off-white amorphous solid. MS (ESI pos. ion) m/z: 354 (MH+). Calc'd exact mass for C11H14BrClN2O2S: 353. 1H NMR (400 MHz, chloroform-d): 1.15-1.35 (m, 2H), 1.52-1.66 (m, 1H), 1.70 (d, J=4.52 Hz, 1H), 1.73 (s, 1H), 1.76-1.86 (m, 1H), 1.92 (d, J=11.54 Hz, 1H), 2.11-2.22 (m, 2H), 2.96-3.05 (m, 1H), 6.70 (s, 1H), 8.15-8.22 (m, 2H).

Provenance & Evidence