反应详情

N-(3-Cyanophenyl)-N′-(piperidin-4-yl)cycloheptylurea (2.07 g, 6.95 mmol) in tetrahydrofuran (100 ml) with triethylamine (7.64 mmol, 0.77 g, 1.1 ml) was cooled to 0° C. and a-toluenesulfonyl chloride (1.46 g, 7.64 mmol) in tetrahydrofuran (60 ml) was added dropwise. The reaction was allowed to cool to ambient temperature and was stirred for 18 h. The solvent was removed in vacuo and the residue patitioned between water and 5:1 ethyl acetate:acetone. The organic layer was washed with 1N HCl and 1N NaOH, then brine. It was dried (Na2SO4) and evaporated to give 2.63 g of crude product. Purification by medium pressure liquid chromatography on a silica gel column (350 g) gave N-(3-cyanophenyl)-N′-(1-((phenyl)methane)sulfonyl)piperidin-4-yl)cycloheptylurea (1.81 g, 4.0 mmol, 58%, mp 203-204° C.); HRMS (M+H)+ calc. 453.196038, found 453.198085.

1. customThe solvent was removed in vacuo
2. washThe organic layer was washed with 1N HCl and 1N NaOH
3. dry with materialIt was dried (Na2SO4)
4. customevaporated
5. customto give 2.63 g of crude product
6. customPurification by medium pressure liquid chromatography on a silica gel column (350 g)