【结 构 式】 |
【药物名称】 【化学名称】 【CA登记号】 【 分 子 式 】C20H26N2O5S 【 分 子 量 】406.50462 |
【开发单位】 【药理作用】0 |
合成路线1
Condensation of D-isoleucine (I) with 4-methoxy-benzenesulfonyl chloride (II) in the presence of Et3N afforded sulfonyl derivative (III), which was subsequently converted to tert-butyl ester (V) upon treatment with dimethylformamide di-tert-butyl acetal (IV). Alkylation of (V) with benzyl bromide and K2CO3 in DMF provided the N-benzyl compound (VI). Then, the tert-butyl ester of (VI) was deprotected with HCl in CH2Cl2, and the resulting carboxylic acid (VII) was condensed with O-tert-butyl hydroxylamine using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide-HCl (EDC) and 1-hydroxybenzotriazole (HOBt) to give the tert-butyl hydroxamate (VIII). The target hydroxamic acid was then obtained by deprotection of (VIII) with HCl in dichloroethane containing one equivalent of EtOH.
【1】 MacPherson, L.J.; et al.; Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits. J Med Chem 1997, 40, 16, 2525. |
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) | 21073 | (2R,3S)-2-amino-3-methylpentanoic acid | C6H13NO2 | 详情 | 详情 | |
(II) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
(III) | 21075 | (2R,3S)-2-[[(4-methoxyphenyl)sulfonyl]amino]-3-methylpentanoic acid | C13H19NO5S | 详情 | 详情 | |
(IV) | 21059 | N-[di(tert-butoxy)methyl]-N,N-dimethylamine; di(tert-butoxy)-N,N-dimethylmethanamine | 36805-97-7 | C11H25NO2 | 详情 | 详情 |
(V) | 21077 | tert-butyl (2R,3S)-2-[[(4-methoxyphenyl)sulfonyl]amino]-3-methylpentanoate | C17H27NO5S | 详情 | 详情 | |
(VI) | 21078 | tert-butyl (2R,3S)-2-[benzyl[(4-methoxyphenyl)sulfonyl]amino]-3-methylpentanoate | C24H33NO5S | 详情 | 详情 | |
(VII) | 21079 | (2R,3S)-2-[benzyl[(4-methoxyphenyl)sulfonyl]amino]-3-methylpentanoic acid | C20H25NO5S | 详情 | 详情 | |
(VIII) | 21080 | (2R,3S)-2-[benzyl[(4-methoxyphenyl)sulfonyl]amino]-N-(tert-butoxy)-3-methylpentanamide | C24H34N2O5S | 详情 | 详情 |