反应详情

温度

100 °C

A solution of (oxydi-2,1-phenylene)bis-(diphenylphosphine) (DPEphos) (43 mg, 0.08 mmol) and tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.02 mmol) in N-methylpyrrolidinone (10 ml) was stirred at room temperature for 5 minutes under nitrogen. 4-(Piperidine-1-sulfonyl)-benzenethiol (121 mg, 0.4 mmol), 2-(2,4-dichloro-benzenesulfonylamino)-5-iodo-isonicotinic acid pentyl ester (218 mg, 0.4 mmol) and potassium t-butoxide (90 mg, 0.8 mmol) were added and the reaction stirred overnight at 100° C. The solvent was removed under reduced pressure and the residue taken up in chloroform. The chloroform solution was washed with brine (25 ml), dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate 2/3 hexane as eluent to afford 2-(2,4-dichloro-benzenesulfonylamino)-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinic acid pentyl ester as a yellow foam (15 mg, 6%). 1H NMR (CDCl3): 10.82 (1H, s, NH); 8.17 (1H, s, Ar); 8.09 (1H, d, Ar); 7.61 (2 H, m, Ar); 7.57 (1H, s, Ar); 7.38 (4H, m, py and Ar); 4.22 (2H, t, OCH2); 2.90 (4H, m, 2×CH2N pip); 1.66 (2H, m, OCH2CH2); 1.54 (4H, m, 2×CH2 pip); 1.33 (4H, m OCH2CH2CH2CH2CH3); 1.19 (2H, m, CH2 pip); 0.88 (3H, t, CH2CH3). HPLC (Luna 2, Gradient 5): rt=7.82 minutes. LCMS rt=8.34 minutes, 673 (M+H)+.

1. customThe solvent was removed under reduced pressure
2. washThe chloroform solution was washed with brine (25 ml)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by flash column chromatography