• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】69292

【品名】4-isopropylthiazole-2-carbonyl chloride

【CA登记号】 

【 分 子 式 】C7H8ClNOS

【 分 子 量 】189.665

【元素组成】C 44.33% H 4.25% Cl 18.69% N 7.38% O 8.44% S 16.91%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXXIV)

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
Extended Information