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【结 构 式】 
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【药物名称】T-0162 【化学名称】N-[3-(tert-Butyl)-2-hydroxy-5-methoxyphenyl]-N'-(3-pyridylmethyl)urea hydrochloride 【CA登记号】195312-36-8, 195315-01-6 (free base) 【 分 子 式 】C18H24ClN3O3 【 分 子 量 】365.86328 |
【开发单位】Tanabe Seiyaku (Originator) 【药理作用】Acute Myocardial Infarction, Treatment of, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Free Radical Scavengers |
合成路线1
Diazotization of p-anisidine (I), followed by coupling of the resulting diazonium salt (II) with 3-tert-butyl-4-hydroxyanisole (III) produced azobenzene (IV). Subsequent protection of the hydroxyl group of (IV) with chloromethyl methyl ether in the presence of NaH afforded the methoxymethyl derivative (V). Aniline (VI) was then obtained by catalytic hydrogenation of (V) over Pd/C. Condensation of aniline (VI) with triphosgene, followed by reaction with 3-picolylamine (VII) gave rise to urea (VIII). The methoxymethyl protecting group of (VIII) was finally removed by treatment with methanolic HCl.
| 【1】 Nakao, K.; et al.; Quantitative structure-activity analyses of novel hydroxyphenylurea derivatives as antioxidants. Bioorg Med Chem 1998, 6, 6, 849. |
| 【2】 Suzuki, T.; Ohmizu, H.; Hashimura, Y.; Kubota, H.; Tanaka, K. (Tanabe Seiyaku Co., Ltd.); Phenol-derivs. having pharmaceutical activity and process for preparing the same. EP 0790240; JP 1998195037; US 5849732 . |
| 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) | 10478 | p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine | 104-94-9 | C7H9NO | 详情 | 详情 |
| (II) | 12149 | 1-(4-Methoxyphenyl)diazonium chloride | C7H7ClN2O | 详情 | 详情 | |
| (III) | 40700 | 2-(tert-butyl)-4-methoxyphenol | C11H16O2 | 详情 | 详情 | |
| (IV) | 40701 | 2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol | C18H22N2O3 | 详情 | 详情 | |
| (V) | 40702 | (Z)-1-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-2-(4-methoxyphenyl)diazene; 3-(tert-butyl)-4-(methoxymethoxy)-5-[(Z)-2-(4-methoxyphenyl)diazenyl]phenyl methyl ether | C20H26N2O4 | 详情 | 详情 | |
| (VI) | 40703 | 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenylamine; 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)aniline | C13H21NO3 | 详情 | 详情 | |
| (VII) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
| (VIII) | 40704 | N-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N'-(3-pyridinylmethyl)urea | C20H27N3O4 | 详情 | 详情 |