【结 构 式】 |
【药物名称】 【化学名称】 【CA登记号】 【 分 子 式 】C18H23N3O5S 【 分 子 量 】393.46511 |
【开发单位】 【药理作用】0 |
合成路线1
Condensation of D-valine (I) with 4-methoxybenzenesulfonyl 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 2-picolyl chloride-HCl (VI) and K2CO3 in DMF provided the N-(2-picolyl) compound (VII). Then, the tert-butyl ester of (VII) was deprotected with HCl in CH2Cl2, and the resulting carboxylic acid (VIII) was condensed with O-tert-butyl hydroxylamine using N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide-HCl (EDC) and 1-hydroxybenzotriazole (HOBt) to give the tert-butyl hydroxamate (IX). The target hydroxamic acid was then obtained by deprotection of (IX) 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. |
【2】 MacPherson, L.J.; Parker, D.T.; Jeng, A.Y. (Novartis Corp.); Arylsulfonamido-substd. hydroxamic acids. US 5506242; US 5552419 . |
【3】 MacPherson, L.J.; Parker, D.T. (Novartis Corp.); Arylsulfonamido-substd. hydroxamic acids. US 5646167 . |
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) | 21056 | (R)-(-)-Valine; D-Valine; (R)-alpha-Aminoisovaleric acid | 640-68-6 | C5H11NO2 | 详情 | 详情 |
(II) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
(III) | 21058 | (2R)-2-[[(4-methoxyphenyl)sulfonyl]amino]-3-methylbutyric acid | C12H17NO5S | 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) | 21060 | tert-butyl (2R)-2-[[(4-methoxyphenyl)sulfonyl]amino]-3-methylbutanoate | C16H25NO5S | 详情 | 详情 | |
(VI) | 21061 | 2-(chloromethyl)pyridine hydrochloride | 6959-47-3 | C6H7Cl2N | 详情 | 详情 |
(VII) | 21062 | tert-butyl (2R)-2-[[(4-methoxyphenyl)sulfonyl](2-pyridinylmethyl)amino]-3-methylbutanoate | C22H30N2O5S | 详情 | 详情 | |
(VIII) | 21063 | (2R)-2-[[(4-methoxyphenyl)sulfonyl](2-pyridinylmethyl)amino]-3-methylbutyric acid hydrochloride | C18H23ClN2O5S | 详情 | 详情 | |
(IX) | 21064 | (2R)-N-(tert-butoxy)-2-[[(4-methoxyphenyl)sulfonyl](2-pyridinylmethyl)amino]-3-methylbutanamide | C22H31N3O5S | 详情 | 详情 |