反应详情

温度

50 °C

To a solution of 4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidine (440 mg, 1.7 mmol) in dry dimethylformamide (6 mL), under an argon atmosphere was added 1,1-dioxido-2-(4-bromobutyl)-5-chloro-1,2-benzisothiazol-3(2H)-one (615 mg, 1.74 mmol, prepared as shown in Example 22) followed by triethylamine (0.25 mL, 1.8 mmol). This solution was heated at 50° C. for four hours and then cooled to room temperature as water was added. The product was extracted, dried (Na2SO4) and evaporated. The residue was chromatographed on a column of silica gel eluting with a gradient of 0.5-2% methanol/chloroform containing 0.2% NH4OH to give 1,1-dioxido-2-(4-(4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one as a viscous oil. 1H NMR (400 MHz, CDCl3): d 8.02 (s, 1H), 7.84 (quartet, J=8 Hz, 2H), 7.30 (broad d, 1H), 7.05 (broad quintet, 2H), 6.98 (broad d, J=8 Hz, 1H), 4.40 (multiplet, 1H), 3.84 (t, J=7.1 Hz, 4H), 3.07 (broad d, J=11.1 Hz, 2H),2.43-2.47 (m, 4H),2.14 (broad t, J=11 Hz, 2H), 1.88-1.93 (quintet, 2H), 1.75-1.81 (multiplet, 4H), 1.62-1.66 (multiplet, 2H), 0.97 (t, J=7.3 Hz, 3H). This oil was converted to its hydrochloride salt and crystallized from methanol upon addition of diethyl ether to give a crystalline white solid, melting point 225-227° C.: Analysis calculated for C26H31ClN4O4S.HCl: C, 55.02; H, 5.68; N, 9.87; found: C, 54.76; H, 5.66; N, 9.80.

1. additionwas added
2. extractionThe product was extracted
3. dry with materialdried (Na2SO4)
4. customevaporated
5. customThe residue was chromatographed on a column of silica gel eluting with a gradient of 0.5-2% methanol/chloroform containing 0.2% NH4OH