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【结 构 式】

【药物名称】

【化学名称】3-(N-Acetyl-N-hydroxyamino)propylphosphonic acid bis(4-methoxyphenyl) diester

【CA登记号】

【 分 子 式 】C19H24NO7P

【 分 子 量 】409.37943

【开发单位】Jomaa Pharma (Originator), Justus-Liebeg-Universität Giessen (Originator), Philipps-Universität Marburg (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Antimalarials, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Treatment of Protozoal Diseases

合成路线1

The reaction of 1,3-dibromopropane (I) with triethyl phosphite (II) at 160 C gives triethyl 3-bromopropylphosphonate (III), which is treated with Tms-Br and water to yield the corresponding phosphonic acid (IV). The reaction of (IV) with PCl3 in refluxing chloroform affords the acyl chloride (V), which is treated with 4-methoxyphenol (VI) and pyridine to provide the expected 4-methoxyphenyl diester (VII). The reaction of (VII) with N,O-bis(tert-butoxycarbonyl)hydroxylamine (VIII) by means of NaH in DMF gives the fully protected hydroxyamino derivative (IX), which by treatment with TFA in dichloromethane yields 3-(hydroxyamino)propylphosphonic acid 4-methoxyphenyl diester (X). Finally, this compound is acylated with Ac-Cl and TEA in ethyl ether to afford the target N-acetylhydroxyamino compound.

1 Reichenberg, A.; et al.; Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity. Bioorg Med Chem Lett 2001, 11, 6, 833.
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) 12581 1,3-Dibromopropane 109-64-8 C3H6Br2 详情 详情
(II) 15487 triethyl phosphite 122-52-1 C6H15O3P 详情 详情
(III) 39080 diethyl 3-bromopropylphosphonate C7H16BrO3P 详情 详情
(IV) 39105 3-bromopropylphosphonic acid 1190-09-6 C3H8BrO3P 详情 详情
(V) 49412 3-bromopropylphosphonic dichloride C3H6BrCl2OP 详情 详情
(VI) 32744 4-methoxyphenol 150-76-5 C7H8O2 详情 详情
(VII) 49413 bis(4-methoxyphenyl) 3-bromopropylphosphonate C17H20BrO5P 详情 详情
(VIII) 34722 2-[([[(tert-butoxycarbonyl)amino]oxy]carbonyl)oxy]-2-methylpropane C10H19NO5 详情 详情
(IX) 49414 5-(tert-butoxycarbonyl)-1,1-bis(4-methoxyphenoxy)-9,9-dimethyl-1,7-dioxo-6,8-dioxa-5-aza-1lambda(5)-phosphadecane C27H38NO10P 详情 详情
(X) 49415 bis(4-methoxyphenyl) 3-(hydroxyamino)propylphosphonate C17H22NO6P 详情 详情
Extended Information