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【结 构 式】 
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【药物名称】SEA-0400 【化学名称】2-[4-(2,5-Difluorobenzyloxy)phenoxy]-5-ethoxyphenylamine 【CA登记号】223104-29-8, 223104-09-4 (HCl) 【 分 子 式 】C21H19F2NO3 【 分 子 量 】371.38728 |
【开发单位】Taisho (Originator) 【药理作用】Acute Myocardial Infarction, Treatment of, CARDIOVASCULAR DRUGS, Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Na+/Ca2+ Exchange Inhibitors |
合成路线1
The reaction of 4-chloro-3-nitrophenol (I) with ethyl iodide and K2CO3 in hot acetone gives the aryl ether (II), which is condensed with 4-benzyloxyphenol (III) by means of t-BuOK in DMF at 150 C to yield the adduct (IV). The reductive debenzylation of (IV), with simultaneous reduction of the nitro group by means of H2 over Pd/C in THF/ethanol affords 5-ethoxy-2-(4-hydroxyphenoxy)aniline (V), which is finally condensed with 2,5-difluorobenzyl bromide (VI) by means of tBu-OK in DMF to provide the target aniline.
| 【1】 Tomisawa, K.; Taguchi, M.; Nakanishi, M.; Ota, T.; Aibe, I. (Taisho Pharmaceutical Co., Ltd.); 2-Phenoxyaniline derivs.. EP 1031556; JP 1999193263; US 6162832; WO 9920598 . |
| 【2】 Taguchi, M.; Ohta, T.; Nakanishi, M.; Tomizawa, K.; Soube, I. (Taisho Pharmaceutical Co., Ltd.); Na+/Ca2+ exchange inhibitors. JP 2000355537 . |
| 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) | 57419 | 3-Nitro-4-chlorophenol; 4-Chloro-3-nitrophenol | 610-78-6 | C6H4ClNO3 | 详情 | 详情 |
| (II) | 57420 | 4-chloro-3-nitrophenyl ethyl ether; 1-chloro-4-ethoxy-2-nitrobenzene | C8H8ClNO3 | 详情 | 详情 | |
| (III) | 18956 | 4-(Benzyloxy)phenol; 4-Benzyloxyphenol | 103-16-2 | C13H12O2 | 详情 | 详情 |
| (IV) | 57421 | 1-[4-(benzyloxy)phenoxy]-4-ethoxy-2-nitrobenzene; benzyl 4-(4-ethoxy-2-nitrophenoxy)phenyl ether | C21H19NO5 | 详情 | 详情 | |
| (V) | 57422 | 4-(2-amino-4-ethoxyphenoxy)phenol | C14H15NO3 | 详情 | 详情 | |
| (VI) | 57423 | 2,5-Difluorobenzyl bromide; alpha-Bromo-2,5-difluorotoluene | 85117-99-3 | C7H5BrF2 | 详情 | 详情 |