反应详情

4-Methylpiperazine-1-sulfonyl chloride hydrochloride (227 mg, 0.966 mmol) was added at room temperature to a solution of 1-(4-fluorophenyl)-3-(piperidin-4-yloxy)urea hydrochloride (140 mg, 0.483 mmol) and K2CO3 (200 mg, 1.45 mmol) in H2O-dioxane (1:1, 4 ml), and the whole was stirred at room temperature for 18 hours. The reaction was quenched with K2CO3 (200 mg) in H2O (10 ml), extracted with ethyl acetate (20 ml×3). The combined organic layer was washed with brine (10 ml), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (chloroform/methanol: 90/10) to give 1-(4-fluorophenyl)-3-(1-(4-methylpiperazin-1-ylsulfonyl)piperidin-4-yloxy)urea (139 mg, 69%) as pale yellow amorphous: LCMS: 416 [M+1]+. 1H NMR (DMSO-d6) δ: 1.72 (m, 2H), 1.93 (m, 2H), 2.19 (s, 3H), 2.35 (m, 4H), 3.01-3.13 (m, 6H), 3.45 (m, 2H), 3.85 (m, 1H), 7.11 (m, 2H), 7.55 (m, 2H), 8.68 (s, 1H), 9.45 (s, 1H).

1. customThe reaction was quenched with K2CO3 (200 mg) in H2O (10 ml)
2. extractionextracted with ethyl acetate (20 ml×3)
3. washThe combined organic layer was washed with brine (10 ml)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (chloroform/methanol: 90/10)