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【结 构 式】 
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【分子编号】68041 【品名】1-(2-bromo-6-fluorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea 【CA登记号】 |
【 分 子 式 】C15H11BrF4N2O2 【 分 子 量 】407.162 【元素组成】C 44.25% H 2.72% Br 19.62% F 18.66% N 6.88% O 7.86% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Condensation of 2-fluoroaniline (XIV) or 2-bromo-6-fluoroaniline (I) with 2-methoxy-5-(trifluoromethyl)phenyl isocyanate (V) in refluxing acetonitrile yields the corresponding diaryl ureas (XV) or (XVI), respec-tively. The N-(2-Fluorophenyl)urea derivative (XV) is then condensed with methyl acrylate (II) by means of Pd(OAc)2 and H2S2O7 in AcoH to give the corresponding (E)-cinnamate (XVII), which finally undergoes intramolecular Michael addition in the presence of DBU in refluxing acetone .
Alternatively, intermediate (XI) is obtained by Heck coupling of aryl bromide (XVI) with methyl acrylate (II) in the presence of Pd(MeCn)2Cl2, (o-tol)3P and Et3n in isobutyronitrile at 90-102 °C .
| 【1】 Goossen, K., Kuhn, o., Berwe, M., Krueger, J., Militzer, H.-C. (Bayer HealthCare AG). Method for producing dihydroquinazolines. Cn 101863843, DE 10227517, EP 1893587, JP 2008543797, US 2009221822, US 8084604, US 2012130072, US 8372972, Wo 2006133822. |
| 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) | 68030 | 2-bromo-6-fluoroaniline | 65896-11-9 | C6H5BrFN | 详情 | 详情 |
| (II) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (V) | 68033 | 2-methoxy-5-(trifluoromethyl)phenyl isocyanate | 16588-75-3 | C9H6F3NO2 | 详情 | 详情 |
| (XI) | 68037 | methyl 2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetate | C19H16F4N2O4 | 详情 | 详情 | |
| (XIV) | 22296 | 2-fluorophenylamine; 2-fluoroaniline | 348-54-9 | C6H6FN | 详情 | 详情 |
| (XV) | 68040 | 1-(2-fluorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea | C15H12F4N2O2 | 详情 | 详情 | |
| (XVI) | 68041 | 1-(2-bromo-6-fluorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea | C15H11BrF4N2O2 | 详情 | 详情 | |
| (XVII) | 68042 | (E)－methyl 3-(3-fluoro-2-(3-(2-methoxy-5-(trifluoromethyl)phenyl)ureido)phenyl)acrylate | C19H16F4N2O4 | 详情 | 详情 |