反应详情

To a solution of 3-(2,4-dichloro-5-methylphenylsulfonylamino)-6-chloropyridazine (by reaction of 3-amino-6-chloropyridazine and 2,4-dichloro-5-methylphenylsulfonyl chloride (100 mg, 0.28 mmol) in 1-methyl-2-pyrrolidinone (1 mL) was added 4-(N-piperidinylsulfonyl)thiophenol (80 mg, 0.31 mmol), potassium tert-butoxide (37 mg, 0.33 mmol), tris(dibenzylideneacetone)dipalladium (0) (25 mg, 27 μmol) and (oxydi-2,1-phenylene)bis-(diphenylphosphine) (30 mg, 56 μmol). The mixture was stirred using a vortex stirrer until homogeneous, sealed under nitrogen, and microwaved at 120° C. for 5 minutes using powerMAX™. The reaction mixture was then added to ethyl acetate (50 mL), extracted with sodium bicarbonate (sat., aq., 3×25 mL), dried over magnesium sulphate, and concentrated under reduced pressure to a dark brown oil. Flash chromatography (SiO2, ethyl acetate:cyclohexane 1:2) afforded a pale yellow solid (32 mg, 20%). 1H NMR (CDCl3): 7.98 & 7.39 (2×1 H, 2×s, A-ring CH's), 7.73 & 7.5 (2×2 H, 2×d, 2×J 10 Hz, Ar CH's of C-ring), 7.15 & 7.08 (2×1 H, 2×d, 2×J 12 Hz, B-ring CH's), 2.99-2.92 (4H, m, CH2NCH2), 2.32 (3H, s, CH3), 1.65-1.53 (4 H, m, CH2CH2CH2CH2CH2), 1.43-1.30 (2 H, m, CH2CH2CH2CH2CH2). Hplc (Luna 2, Gradient 5): rt=6.38 minutes. LC/MS rt=7.15 minutes, 573/575 (MH+).

1. customsealed under nitrogen
2. custommicrowaved at 120° C. for 5 minutes
3. extractionextracted with sodium bicarbonate (sat., aq., 3×25 mL)
4. dry with materialdried over magnesium sulphate
5. concentrationconcentrated under reduced pressure to a dark brown oil