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【结 构 式】 
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【分子编号】29183 【品名】[6-(benzyloxy)-2-(dimethylamino)-1-benzothiophen-3-yl](3-methoxy-4-[[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]oxy]phenyl)methanone 【CA登记号】 |
【 分 子 式 】C35H40N2O4S 【 分 子 量 】584.77968 【元素组成】C 71.89% H 6.89% N 4.79% O 10.94% S 5.48% |
合成路线1
该中间体在本合成路线中的序号：(X)Condensation of 4-(benzyloxy)benzaldehyde (VII) with N,N-dimethyl thioformamide (A) in the presence of LDA at -78 C generated the alpha-hydroxythioamide (VIII), which was cyclized by means of methanesulfonic acid to afford benzothiophene (IX). Friedel-Crafts acylation of (IX) with acid chloride (VI) upon heating in chlorobenzene yielded the 3-acyl benzothiophene (X). Subsequent displacement of the dimethylamino group of (X) by Grignard reagent (XI) produced the 2-aryl benzothiophene (XII). Deoxygenation of the keto group of (XII) was accomplished by the sequence of reduction to alcohol (XIII) with LiAlH4, followed by treatment with Et3SiH in trifluoroacetic acid to give (XIV). The benzyl ether of (XIV) was finally deprotected by hydrogenation over Pd/C to furnish the title compound.
| 【1】 McCowan, J.R.; Sall, D.J.; Gifford-Moore, D.S.; Takeuchi, K.; Denney, M.L.; Kohn, T.J.; Smith, G.F.; Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of hydroxybenzo[b]thiophenes. Bioorg Med Chem Lett 1999, 9, 5, 759. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 29180 | dimethylthioformamide | 758-16-7 | C3H7NS | 详情 | 详情 |
| (VI) | 29178 | 3-methoxy-4-[[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]oxy]benzoyl chloride | C18H24ClNO3 | 详情 | 详情 | |
| (VII) | 29179 | 4-(Benzyloxy)benzaldehyde | 4397-53-9 | C14H12O2 | 详情 | 详情 |
| (VIII) | 29181 | 2-[4-(benzyloxy)phenyl]-2-hydroxy-N,N-dimethylethanethioamide | C17H19NO2S | 详情 | 详情 | |
| (IX) | 29182 | 6-(benzyloxy)-N,N-dimethyl-1-benzothiophen-2-amine | C17H17NOS | 详情 | 详情 | |
| (X) | 29183 | [6-(benzyloxy)-2-(dimethylamino)-1-benzothiophen-3-yl](3-methoxy-4-[[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]oxy]phenyl)methanone | C35H40N2O4S | 详情 | 详情 | |
| (XI) | 29184 | bromo[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]magnesium | C12H16BrMgNO | 详情 | 详情 | |
| (XII) | 29185 | (6-(benzyloxy)-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-1-benzothiophen-3-yl)(3-methoxy-4-[[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]oxy]phenyl)methanone | C45H50N2O5S | 详情 | 详情 | |
| (XIII) | 29186 | (6-(benzyloxy)-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-1-benzothiophen-3-yl)(3-methoxy-4-[[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]oxy]phenyl)methanol | C45H52N2O5S | 详情 | 详情 | |
| (XIV) | 29187 | 1-(2-[4-[6-(benzyloxy)-3-(3-methoxy-4-[[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]oxy]benzyl)-1-benzothiophen-2-yl]phenoxy]ethyl)pyrrolidine | C45H52N2O4S | 详情 | 详情 |