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【结 构 式】 
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【分子编号】69163 【品名】2-(2-chloro-5-nitrophenyl)pyridine 【CA登记号】 |
【 分 子 式 】C11H7ClN2O2 【 分 子 量 】234.642 【元素组成】C 56.31% H 3.01% Cl 15.11% N 11.94% O 13.64% |
合成路线1
该中间体在本合成路线中的序号：(IV)Sandmeyer reaction of 2-chloro-5-nitroaniline (I) with NaNO2 in the presence of KI gives 1-chloro-2-iodo-4-nitrobenzene (II), which is then coupled with (2-pyridyl)zinc iodide (III) by means of Pd(PPh3)4, tris(2-furyl)phosphine and CuI in THF/DMAc to provide the phenylpyridine derivative (IV). After nitro group reduction in compound (IV) using either Fe and AcOH at 80 °C or SnCl2 and HCl in EtOH , the resulting pyridylaniline (V) is finally acylated with either 2-chloro-4-(methylsulfonyl)benzoyl chloride (VI) in the presence of Et3N in CH2Cl2 or 2-chloro-4-(methylsulfonyl)benzoic acid (VII) by means of HATU and DIEA in DMF .
| 【1】 Robarge, K.D., Brunton, S.A., Castanedo, G.M. et al. GDC-0449 - A potent inhibitor of the hedgehog pathway. Bioorg Med Chem Lett 2009, 19(19): 5576-81. |
| 【2】 Gunzner, J., Sutherlin, D., Stanley, M. et al. (Genentech, Inc.; Curis, Inc.). Pyridyl inhibitors of hedgehog signalling. EP 1789390, JP 2008511675, WO 2006028958. |
| 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) | 43033 | 2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine | 6283-25-6 | C6H5ClN2O2 | 详情 | 详情 |
| (II) | 69162 | 1-chloro-2-iodo-4-nitrobenzene;4-Chloro-3-iodonitrobenzene | 74534-15-9 | C6H3ClINO2 | 详情 | 详情 |
| (III) | 69164 | (2-pyridyl)zinc iodide | C5H4INZn | 详情 | 详情 | |
| (IV) | 69163 | 2-(2-chloro-5-nitrophenyl)pyridine | C11H7ClN2O2 | 详情 | 详情 | |
| (V) | 69165 | 4-chloro-3-(pyridin-2-yl)aniline | C11H9ClN2 | 详情 | 详情 | |
| (VI) | 69166 | 2-chloro-4-(methylsulfonyl)benzoyl chloride;2-chloro-5-(methylsulfonyl)benzoyl chloride | C8H6Cl2O3S | 详情 | 详情 | |
| (VII) | 69167 | 2-chloro-4-(methylsulfonyl)benzoic acid;2-chloro-5-(methylsulfonyl)benzoic acid | 89938-62-5 | C8H7ClO4S | 详情 | 详情 |