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【结 构 式】 
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【药物名称】Nizatidine, ZE-101, ZL-101, LY-139037, Zanizal, Nizax, Acinon, Axid 【化学名称】N-[2-[2-[(Dimethylamino)methyl]-4-thiazolylmethylthio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine 【CA登记号】76963-41-2 【 分 子 式 】C12H21N5O2S2 【 分 子 量 】331.46147 |
【开发单位】Lilly (Originator), Italfarmaco (Licensee), Reliant Pharmaceuticals (Licensee), Zeria (Licensee) 【药理作用】Agents for Gastritis, Antiulcer Drugs, Esophageal Diseases, Treatment of, Gastric Antisecretory Drugs, Gastroesophageal Reflux Disease, Agents for, GASTROINTESTINAL DRUGS, Histamine H2 Receptor Antagonists |
合成路线1
The cyclization of dimethylaminothioacetamide (I) with ethyl bromopyruvate (II) in refluxing ethanol gives ethyl 2-(dimethylaminomethyl)-4-thiazolecarboxylate (III), which is reduced with lithium triethyl borohydride in THF yielding 2-(dimethylaminomethyl)-4-thiazolemethanol (IV). The condensation of (IV) with 2-aminoethanethiol (V) by means of 48% HBr affords 2-(dimethylaminomethyl)-4-(2-aminoethylthiomethyl)thiazole (VI), which is finally condensed with 1-(methylthio)-2-nitro-N-methylethyleneamine (VII) in water.
| 【1】 Pioch, R.P. (Eli Lilly and Company); N-Methyl-N'-2-[[(2-dimethylaminomethyl)-4-thiazolyl]methylthio]ethyl-2-nitro-1,1-ethenediamine. EP 0049618; GB 2084581; JP 57091980; US 4375547 . |
| 【2】 Serradell, M.N.; Castaner, J.; Nizatidine. Drugs Fut 1984, 9, 9, 655. |
| 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) | 30602 | 2-(dimethylamino)ethanethioamide | C4H10N2S | 详情 | 详情 | |
| (II) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |
| (III) | 30603 | ethyl 2-[(dimethylamino)methyl]-1,3-thiazole-4-carboxylate | C9H14N2O2S | 详情 | 详情 | |
| (IV) | 30604 | [2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methanol | C7H12N2OS | 详情 | 详情 | |
| (V) | 13186 | 2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine | 60-23-1 | C2H7NS | 详情 | 详情 |
| (VI) | 30605 | N-[(4-[[(2-aminoethyl)sulfanyl]methyl]-1,3-thiazol-2-yl)methyl]-N,N-dimethylamine; 2-[([2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methyl)sulfanyl]-1-ethanamine | C9H17N3S2 | 详情 | 详情 | |
| (VII) | 13852 | N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine; (E)-N-Methyl-1-(methylsulfanyl)-2-nitro-1-ethenamine; (E)-1-Methylthio-1-methylamino-2-nitroethylene | 61832-41-5 | C4H8N2O2S | 详情 | 详情 |