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【结 构 式】

【药物名称】

【化学名称】N-[6-(1H-Imidazol-4-yl)hexyl]naphthalene-2-sulfonamide

【CA登记号】195052-77-8

【 分 子 式 】C19H23N3O2S

【 分 子 量 】357.47806

【开发单位】James Black Foundation (Originator)

【药理作用】Histamine H3 Receptor Antagonists

合成路线1

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
Extended Information