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【结 构 式】 
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【药物名称】 【化学名称】4-[3-(4-Ethynylphenoxy)propyl]-1H-imidazole maleate 【CA登记号】184027-09-6, 184027-08-5 (free base) 【 分 子 式 】C18H18N2O5 【 分 子 量 】342.35456 |
【开发单位】Bioprojet (Originator), INSERM (Originator) 【药理作用】Antiepileptic Drugs, Antinarcoleptic Drugs, Antipsychotic Drugs, Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, Sleep Disorders, Treatment of, Histamine H3 Receptor Antagonists |
合成路线1
4-Iodophenol (I) was protected as the trimethylsilyl ether (II) with Me3SiCl and then coupled with (trimethylsilyl)acetylene (III) using palladium catalyst and CuI to afford the O-desilylated ethynylphenol (IV). This was condensed under Mitsunobu conditions with N-Boc-imidazolylpropanol (VI), prepared from imidazolylpropanol (V) and Boc2O, to afford ether (VII). Deprotection of the Boc group of (VII) with methanolic hydrazine at r.t. yielded a mixture of (VIII) and the fully desilylated analogue (IX), which was isolated by column chromatography and finally crystallized as the maleate salt from EtOH-Et2O.
| 【1】 Krause, M.; Ligneau, X.; Stark, H.; Garbarg, M.; Schwartz, J.C.; Schunack, W.; 4-Alkynylphenyl imidazolylpropyl ethers as selective histamine H3-receptor antagonists with high oral central nervous system activity. J Med Chem 1998, 41, 21, 4171. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22242 | 4-iodophenol | 540-38-5 | C6H5IO | 详情 | 详情 |
| (II) | 22243 | (4-iodophenoxy)(trimethyl)silane; 4-iodophenyl trimethylsilyl ether | C9H13IOSi | 详情 | 详情 | |
| (III) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (IV) | 22245 | 4-[2-(trimethylsilyl)ethynyl]phenol | C11H14OSi | 详情 | 详情 | |
| (V) | 21245 | 3-(1H-imidazol-4-yl)-1-propanol | C6H10N2O | 详情 | 详情 | |
| (VI) | 22247 | tert-butyl 4-(3-hydroxypropyl)-1H-imidazole-1-carboxylate | C11H18N2O3 | 详情 | 详情 | |
| (VII) | 22248 | tert-butyl 4-(3-[4-[2-(trimethylsilyl)ethynyl]phenoxy]propyl)-1H-imidazole-1-carboxylate | C22H30N2O3Si | 详情 | 详情 | |
| (VIII) | 22249 | 4-(3-[4-[2-(trimethylsilyl)ethynyl]phenoxy]propyl)-1H-imidazole; 3-(1H-imidazol-4-yl)propyl 4-[2-(trimethylsilyl)ethynyl]phenyl ether | C17H22N2OSi | 详情 | 详情 | |
| (IX) | 22250 | 4-ethynylphenyl 3-(1H-imidazol-4-yl)propyl ether; 4-[3-(4-ethynylphenoxy)propyl]-1H-imidazole | C14H14N2O | 详情 | 详情 |