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【结 构 式】 
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【分子编号】58441 【品名】2-chloro-1-fluoro-4-nitrobenzene; 3-Chloro-4-fluoronitrobenzene; 4-Fluoro-3-chloronitrobenzene 【CA登记号】350-30-1 |
【 分 子 式 】C6H3ClFNO2 【 分 子 量 】175.5464632 【元素组成】C 41.05% H 1.72% Cl 20.2% F 10.82% N 7.98% O 18.23% |
合成路线1
该中间体在本合成路线中的序号：(I)Condensation of 3-chloro-4-fluoronitrobenzene (I) with the sodium derivative of 2-mercapto-1-methylimidazole (II) affords the diaryl sulfide (III). Subsequent nitro group reduction in (III) using iron dust and ammonium chloride provides the intermediate aniline (IV).
| 【1】 Dutia, M.; Powell, D.W.; Berger, D.M.; et al.; Synthesis and evaluation of 4-anilino substituted 3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 105. |
| 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) | 58441 | 2-chloro-1-fluoro-4-nitrobenzene; 3-Chloro-4-fluoronitrobenzene; 4-Fluoro-3-chloronitrobenzene | 350-30-1 | C6H3ClFNO2 | 详情 | 详情 |
| (II) | 18783 | 1-methyl-1H-imidazol-2-ylhydrosulfide; 1-methyl-1H-imidazole-2-thiol | 60-56-0 | C4H6N2S | 详情 | 详情 |
| (III) | 58442 | 2-chloro-4-nitrophenyl 1-methyl-1H-imidazol-2-yl sulfide; 2-[(2-chloro-4-nitrophenyl)sulfanyl]-1-methyl-1H-imidazole | C10H8ClN3O2S | 详情 | 详情 | |
| (IV) | 58443 | 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]aniline; 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]phenylamine | C10H10ClN3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIV)The precursor 3-chloro-4-(2-pyridylmethoxy)aniline (I) is prepared by coupling of 2-chloro-1-fluoro-4-nitrobenzene (XIV) with 2-pyridylmethanol (XV) by means of KOH in acetonitrile to give the 2-chloro-4-nitrophenyl ether (XVI) , which is then reduced to the corresponding aniline (I) by means of H2 over Pt/C or Pd/C in THF, or Zn and NH4Cl in EtOH .
| 【3】 Rabindran, S.K., Tsou, H.-R., Wissner, A. (Wyeth). Protein tyrosine kinase enzyme inhibitors. US 2005059678, US 7399865, WO 2005028443. |
| 【4】 Chew, W., Cheal, G.K., Lunetta, J.F. (Wyeth). Methods of synthesizing substituted 3-cyanoquinolines and intermediates thereof. EP 1883631, JP 2008545688, US 2006270668, WO 2006127207. |
| 【1】 Chew, W., Papamichelakis, M. (Wyeth). Methods of preparing 3-cyanoquinolines and intermediates made thereby. WO 2006127205. |
| 【2】 Wissner, A., Rabindran, S.K., Tsou, H.-R. (Wyeth). Substituted quinolines as protein tyrosine kinase enzyme inhibitors. EP 1670473, WO 2005034955. |
| 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) | 69190 | 3-Chloro-4-(2-pyridylmethoxy)aniline | C12H11ClN2O | 详情 | 详情 | |
| (XIV) | 58441 | 2-chloro-1-fluoro-4-nitrobenzene; 3-Chloro-4-fluoronitrobenzene; 4-Fluoro-3-chloronitrobenzene | 350-30-1 | C6H3ClFNO2 | 详情 | 详情 |
| (XV) | 30208 | 2-pyridinylmethanol；pyridin-2-ylmethanol；2-pyridylmethanol | 586-98-1 | C6H7NO | 详情 | 详情 |
| (XVI) | 69201 | 2-((2-chloro-4-nitrophenoxy)methyl)pyridine;2-chloro-4-nitrophenyl ether | C12H9ClN2O3 | 详情 | 详情 |