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【结 构 式】 
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【药物名称】Anastrozole, ZD-1033, ICI-D1033, Arimidex 【化学名称】2,2'-[5-(1H-1,2,4-Triazol-1-ylmethyl)-1,3-phenylene]bis(2-methylpropionitrile) 【CA登记号】120511-73-1 【 分 子 式 】C17H19N5 【 分 子 量 】293.37448 |
【开发单位】AstraZeneca (Originator), Serono (Licensee) 【药理作用】Breast Cancer Therapy, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, Female Infertility, Agents for, Oncolytic Drugs, Aromatase Inhibitors |
合成路线1
The reaction of alpha,alpha'-dibromomesitylene (I) with potassium cyanide by means of tetrabutylammonium bromide (TBABr) in refluxing dichloromethane water gives 2,2'-(5-methyl-1,3-phenylene)bis(acetonitrile) (II), which is methylated with methyl iodide and NaH in DMF to yield 2,2'-(5-methyl-1,3-phenylene)bis(2-methylpropionitrile) (III). The bromination of (III) with N-bromosuccinimide (NBS) and benzoyl peroxide in CCl4 affords the bromomethyl compound (IV), which is finally condensed with sodium 1,2,4-triazole (V) in DMF.
| 【1】 Mealy, N.; Prous, J.; Castaner, J.; ZD-1033. Drugs Fut 1995, 20, 1, 30. |
| 【2】 Edwards, P.N.; Large, M.W. (AstraZeneca plc); (Substd. aralkyl)heterocyclic cpds. AU 8816911; EP 0296749; JP 1989019067; US 4935437 . |
| 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) | 13176 | 1,3-Bis(bromomethyl)-5-methylbenzene | 19294-04-3 | C9H10Br2 | 详情 | 详情 |
| (II) | 13177 | 2-[3-Methyl-5-(2-nitriloethyl)phenyl]acetonitrile | C11H10N2 | 详情 | 详情 | |
| (III) | 13178 | 2-[3-(1,1-Dimethyl-2-nitriloethyl)-5-methylphenyl]-2-methylpropanenitrile | C15H18N2 | 详情 | 详情 | |
| (IV) | 13179 | 2-[3-(Bromomethyl)-5-(1,1-dimethyl-2-nitriloethyl)phenyl]-2-methylpropanenitrile | C15H17BrN2 | 详情 | 详情 | |
| (V) | 13104 | 1,2,4-Triazole, sodium derivative | 41253-21-8 | C2H2N3Na | 详情 | 详情 |