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【结 构 式】 
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【分子编号】69291 【品名】2-Methyl-3-amino-4-acetylanisole;1-(2-amino-4-methoxy-3-methylphenyl)ethanone 【CA登记号】912347-94-5 |
【 分 子 式 】C10H13NO2 【 分 子 量 】179.21876 【元素组成】C 67.02% H 7.31% N 7.82% O 17.85% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)Curtius rearrangement of 3-methoxy-2-methylbenzoic acid (XXX) by treatment with diphenylphosphonic azide (DPPA) in the presence of Et3N in toluene at 100 °C followed by t-BuOH in refluxing toluene gives N-Boc-3-methoxy-2-methylaniline (XXXI), which upon deprotection by means of TFA in CH2Cl2 and subsequent basification of the obtained TFA salt with NaHCO3 yields 3-methoxy-2-methylaniline (XXXII). Friedel–Crafts acylation of (XXXII) by a previous treatment with boron trichloride (BCl3) in CH2Cl2/xylene followed by the addition of acetonitrile and AlCl3 in CH2Cl2 at 70 °C furnishes the ortho-aminoacetophenone (XXXIII), which upon N-acylation with 4-isopropylthiazole-2-carbonyl chloride (XXXIV) in dioxane affords intermediate (XXXV). Finally, intermediate (XXXV) cyclizes in the presence of t-BuOK in t-BuOH at 100 °C .
| 【1】 Raboisson, P., De Kock, H., Rosenquist, A. et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett 2008, 18(17): 4853-8. |
| 【2】 Stokbroekx, S.C.M., Leys, C., Swinney, K.A., Wuyts, S., Horvath, A. (Tibotec Pharmaceuticals Ltd.). Polymorphic forms of a macrocyclic inhibitor of HCV. WO 2008092954. |
| 【3】 Raboisson, P.J.-M.B., De Kock, H.A., Hu, L. et al. (Tibotec Pharmaceuticals Ltd.; Medivir AB). Macrocyclic inhibitors of hepatitis C virus. CA 2616580, EP 1912999, JP 2009502889, WO 2007014926. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 69272 | 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-2-4-Quinolinol;(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-ol | 923289-21-8 | C17H18N2O2S | 详情 | 详情 |
| (XXX) | 69288 | 2-methyl-m-Anisicacid;3-Methoxy-o-toluic acid;3-methoxy-2-methylbenzoic acid | 55289-06-0 | C9H10O3 | 详情 | 详情 |
| (XXXI) | 69289 | tert-butyl (3-methoxy-2-methylphenyl)carbamate | C13H19NO3 | 详情 | 详情 | |
| (XXXII) | 69290 | 3-methoxy-2-methylaniline | 19500-02-8 | C8H11NO | 详情 | 详情 |
| (XXXIII) | 69291 | 2-Methyl-3-amino-4-acetylanisole;1-(2-amino-4-methoxy-3-methylphenyl)ethanone | 912347-94-5 | C10H13NO2 | 详情 | 详情 |
| (XXXIV) | 69292 | 4-isopropylthiazole-2-carbonyl chloride | C7H8ClNOS | 详情 | 详情 | |
| (XXXV) | 69293 | N-(6-acetyl-3-methoxy-2-methylphenyl)-4-isopropylthiazole-2-carboxamide | C17H20N2O3S | 详情 | 详情 |