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【结 构 式】 
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【药物名称】MTEP 【化学名称】3-[2-(2-Methylthiazol-4-yl)ethynyl]pyridine 【CA登记号】329205-68-7 【 分 子 式 】C11H8N2S 【 分 子 量 】200.26381 |
【开发单位】Merck & Co. (Originator) 【药理作用】Anxiolytics, PSYCHOPHARMACOLOGIC DRUGS, mglu5 Antagonists |
合成路线1
Chloroacetyl chloride (I) is condensed with bis(trimethylsilyl)acetylene (II) in the presence of AlCl3 to provide 1-chloro-4-(trimethylsilyl)-3-butyn-2-one (III). Cyclization of chloro ketone (III) with thioacetamide (IV) affords the ethynylthiazole derivative (V). Finally, palladium-catalyzed coupling of (V) with 3-bromopyridine (VI) gives rise to the target diarylacetylene.
| 【1】 Cosford, N.D.P.; Tehrani, L.; Roppe, J.; Schweiger, E.; Smith, N.D.; Anderson, J.; Bristow, L.; Brodkin, J..; Jiang, X.; McDonald, I.; Rao, S.; Washburn, M.; Varney, M.A.; 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]- pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity. J Med Chem 2003, 46, 2, 204. |
| 【2】 McDonald, I.A.; Munoz, B.; Vernier, J.-M.; Cosford, N.D.P.; Varney, M.A.; Hess, S.D.; Bleicher, L.S.; Cube, R.V.; Schweiger, E.J. (Merck & Co., Inc.); Heterocyclic cpds. and methods of use thereof. JP 2003508390; WO 0116121 . |
| 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) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (II) | 27189 | trimethyl[2-(trimethylsilyl)ethynyl]silane | 14630-40-1 | C8H18Si2 | 详情 | 详情 |
| (III) | 63351 | 1-chloro-4-(trimethylsilyl)-3-butyn-2-one | C7H11ClOSi | 详情 | 详情 | |
| (IV) | 19170 | ethanethioamide | 62-55-5 | C2H5NS | 详情 | 详情 |
| (V) | 63352 | 2-methyl-4-[2-(trimethylsilyl)ethynyl]-1,3-thiazole | C9H13NSSi | 详情 | 详情 | |
| (VI) | 13265 | 3-Bromopyridine | 626-55-1 | C5H4BrN | 详情 | 详情 |
Extended Information