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【结 构 式】 
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【分子编号】40702 【品名】(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 【CA登记号】 |
【 分 子 式 】C20H26N2O4 【 分 子 量 】358.43752 【元素组成】C 67.02% H 7.31% N 7.82% O 17.85% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |
合成路线2
该中间体在本合成路线中的序号：(IX)The diazonium salt (VI), prepared by diazotization of p-anisidine (V), was added to 4-methoxy-2-tert-butylphenol (VII) yielding the azo adduct (VIII). Protection of the phenolic hydroxyl group of (VIII) was carried out by alkylation with methoxymethyl chloride and NaH to give methoxymethyl ether (IX). Then, reductive cleavage of the diazo group of (IX) by hydrogenation over Pd/C furnished aniline (X) (1). Subsequent reaction of (X) with triphosgene and triethylamine in cold CH2Cl2 produced isocyanate (XI), which was condensed with amine (IV) to afford urea (XII). After acid deprotection of the methoxymethyl group of (XII), treatment with phosphoric acid in EtOH provided the title triphosphate salt.
| 【1】 Kubota, H.; Suzumura, K.; Suzuki, T.; Ohmizu, H.; Kashimura, Y.; Antioxidative property of T-0970, a new ureidophenol derivative. Free Radical Research 2000, 32, 3, 255. |
| 【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 |
|---|---|---|---|---|---|---|
| (IV) | 41432 | N-(3-pyridinyl)-N-(4-pyridinylmethyl)amine; N-(4-pyridinylmethyl)-3-pyridinamine | C11H11N3 | 详情 | 详情 | |
| (V) | 10478 | p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine | 104-94-9 | C7H9NO | 详情 | 详情 |
| (VI) | 41433 | 4-methoxybenzenediazonium | C7H7N2O | 详情 | 详情 | |
| (VII) | 40700 | 2-(tert-butyl)-4-methoxyphenol | C11H16O2 | 详情 | 详情 | |
| (VIII) | 40701 | 2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol | C18H22N2O3 | 详情 | 详情 | |
| (IX) | 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 | |
| (X) | 40703 | 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenylamine; 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)aniline | C13H21NO3 | 详情 | 详情 | |
| (XI) | 41434 | 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl isocyanate; 1-(tert-butyl)-3-isocyanato-5-methoxy-2-(methoxymethoxy)benzene | C14H19NO4 | 详情 | 详情 | |
| (XII) | 41435 | N'-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N-(3-pyridinyl)-N-(4-pyridinylmethyl)urea | C25H30N4O4 | 详情 | 详情 |