【结 构 式】 |
【分子编号】27987 【品名】5-[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)hexyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide 【CA登记号】 |
【 分 子 式 】C19H24N4O4S 【 分 子 量 】404.49012 【元素组成】C 56.42% H 5.98% N 13.85% O 15.82% S 7.93% |
合成路线1
该中间体在本合成路线中的序号:(V)Lithiation of 1-(N-N-dimethylsulfamoyl)imidazole (I) followed by reaction with tert-butyldimethylsilyl chloride produced the 2-silyl protected imidazole (II). Further lithiation of (II) allowed the introduction of a bromohexyl group at position 5 upon treatment with 1,6-dibromohexane yielding (III). Bromide (III) was subsequently converted into primary amine (VI) through a Gabriel synthesis involving condensation with potassium phthalimide (IV) with concomitant desilylation, and then hydrazinolysis of the resulting alkylated phthalimide (V). Condensation of amine (VI) with naphthalene-2-sulfonyl chloride (VII) furnished sulfonamide (VIII). The sulfamoyl protecting group of (VIII) was finally removed by hydrolysis with HCl.
【1】 Tozer, M.J.; Kalindjian, B.; Pether, M.J.; Watt, G.F.; Shankley, N.P.; Harper, E.A.; From histamine to imidazolylalkyl-sulfonamides: The design of a novel series of histamine H3-receptor antagonists. Bioorg Med Chem Lett 1999, 9, 13, 1825. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 | |
(I) | 11036 | N,N-Dimethyl-1H-imidazole-1-sulfonamide | 78162-58-0 | C5H9N3O2S | 详情 | 详情 |
(II) | 11037 | 2-[tert-Butyl(dimethyl)silyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C11H23N3O2SSi | 详情 | 详情 | |
(III) | 27986 | 5-(6-bromohexyl)-2-[tert-butyl(dimethyl)silyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C17H34BrN3O2SSi | 详情 | 详情 | |
(IV) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 | |
(V) | 27987 | 5-[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)hexyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C19H24N4O4S | 详情 | 详情 | |
(VI) | 27988 | 5-(6-aminohexyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide | C11H22N4O2S | 详情 | 详情 | |
(VII) | 27989 | 2-naphthalenesulfonyl chloride | 93-11-8 | C10H7ClO2S | 详情 | 详情 |
(VIII) | 27990 | N,N-dimethyl-5-[6-[(2-naphthylsulfonyl)amino]hexyl]-1H-imidazole-1-sulfonamide | C21H28N4O4S2 | 详情 | 详情 |