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【结 构 式】 
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【分子编号】30222 【品名】4-(6,7-dihydro-1-benzothiophen-4-yl)-1-trityl-1H-imidazole 【CA登记号】 |
【 分 子 式 】C30H24N2S 【 分 子 量 】444.60004 【元素组成】C 81.05% H 5.44% N 6.3% S 7.21% |
合成路线1
该中间体在本合成路线中的序号：(VII)This compound has been obtained by two different ways: 1) The reaction of 4-iodo-1-tritylimidazole (I) with ethylmagnesium bromide produced the Grignard reagent (II). Subsequent addition of (II) to 4,5,6,7-tetrahydrobenzo[b]thiophen-4-one (III) afforded the tertiary alcohol (IV). Finally, acidic treatment of (IV) with methanolic HCl effected both alcohol dehydration and trityl group cleavage to yield the title compound. 2) The reaction of 4-iodo-1-tritylimidazole (I) first with ethylmagnesium bromide to give the Grignard reagent (II) and then with either Bu3SnCl or ZnCl2 gave the respective tin- or zinc-organometallic reagents (V). 4,5,6,7-Tetrahydrobenzo[b]thiophen-4-one (III) was then converted to the corresponding enol triflate (VI) by means of LDA and N-phenyltrifluoromethanesulfonimide (1) or trifluoromethanesulfonic anhydride. Subsequent coupling of (VI) with organometallic (V) in the presence of a palladium catalyst and LiCl in dioxane furnished 4-(1-tritylimidazol-4-yl)-6,7-dihydrobenzo[b]thiophene (VII), which was finally treated with methanolic HCl to perform the cleavage of the trityl group and yield the target compound.
| 【1】 Martinez, R.P.; Baxter, M.; McDonnell, M.E.; Boyd, R.E.; Connelly, C.D.; Codd, E.E.; Lewis, M.E.; Reitz, A.B.; Jetter, M.C.; Ross, T.M.; Synthesis, alpha2 adrenergic receptor binding affinity and in vivo activity of certain imidazole-substituted bicyclic thiophenes. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 111. |
| 【2】 Ross, T.M.; Martinez, R.P.; Jetter, M.C.; McDonnell, M.E.; Boyd, R.E.; Raffa, R.B.; Codd, E.E.; Reitz, A.B.; Lewis, M.A.; Connelly, C.D.; alpha2 Adrenoceptor agonists as potential analgesic agents.2. Discovery of 4-(4-imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene as a high-affinity ligand for the alpha2D adrenergic receptor. J Med Chem 2000, 43, 7, 1423. |
| 【3】 Jetter, M.C.; Baxter, E.W.; McDonnell, M.; Ross, T.M.; Reitz, A.B.; Boyd, R.E. (Ortho-McNeil Pharmaceutical, Inc.); 4-Thionaphthyl-1H-imidazoles with alpha-2-adrenergic activity. WO 9951593 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 30219 | 4-(tributylstannyl)-1-trityl-1H-imidazole | C34H44N2Sn | 详情 | 详情 | |
| (Vb) | 30220 | chloro(1-trityl-1H-imidazol-4-yl)magnesium | C22H17ClMgN2 | 详情 | 详情 | |
| (I) | 30216 | 4-iodo-1-trityl-1H-imidazole | C22H17IN2 | 详情 | 详情 | |
| (II) | 30217 | bromo(1-trityl-1H-imidazol-4-yl)magnesium | C22H17BrMgN2 | 详情 | 详情 | |
| (III) | 11045 | 6,7-Dihydro-1-benzothiophen-4(5H)-one; 4-Keto-4,5,6,7-tetrahydrothianaphthene; Tetrahydrobenzo(b)thiophene-4-one | 13414-95-4 | C8H8OS | 详情 | 详情 |
| (IV) | 30218 | 4-(1-trityl-1H-imidazol-4-yl)-4,5,6,7-tetrahydro-1-benzothiophen-4-ol | C30H26N2OS | 详情 | 详情 | |
| (VI) | 30221 | 6,7-dihydro-1-benzothiophen-4-yl trifluoromethanesulfonate | C9H7F3O3S2 | 详情 | 详情 | |
| (VII) | 30222 | 4-(6,7-dihydro-1-benzothiophen-4-yl)-1-trityl-1H-imidazole | C30H24N2S | 详情 | 详情 |