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【结 构 式】 
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【药物名称】VRC-3783 【化学名称】2-Fluoro-N-methyl-4-[2-oxo-5(S)-(thioacetamidomethyl)oxazolidin-3-yl]benzamide 【CA登记号】324788-52-5 【 分 子 式 】C14H16FN3O3S 【 分 子 量 】325.36432 |
【开发单位】Pfizer (Originator), Vicuron Pharmaceuticals (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Oxazolidinones |
合成路线1
The azidomethyl oxazolidinone (I) was reduced to the corresponding amine (II) by treatment with triphenylphosphine, followed by aqueous hydrolysis of the intermediate iminophosphorane. Condensation of amine (II) with ethyl dithioacetate (III) produced thioacetamide (IV). After acidic cleavage of the tert-butyl ester, the resultant carboxylic acid (V) was converted to the active ester (VI) upon treatment with pentafluorophenyl trifluoroacetate. Finally, displacement of the pentafluorophenyl ester (VI) with methylamine gave rise to the target N-methyl amide.
| 【1】 Luehr, G.W.; Gordeev, M.F.; Gadwood, R.C.; et al.; 4'-Amido phenyloxazolidinone thioamides: Antimicrobial activity and pharmacokinetics in rat. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1047. |
| 【2】 Patel, D.V.; Gadwood, R.C.; Gordeev, M.F.; Luehr, G.W. (Pharmacia Corp.); Oxazolidinones and their use as antiinfectives. EP 1200416; US 6441005; WO 0109107 . |
| 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) | 55908 | tert-butyl 4-[(5R)-5-(azidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzoate | C15H17FN4O4 | 详情 | 详情 | |
| (II) | 58767 | tert-butyl 4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzoate | C15H19FN2O4 | 详情 | 详情 | |
| (III) | 55851 | Ethyl dithioacetate | C4H8S2 | 详情 | 详情 | |
| (IV) | 58768 | tert-butyl 4-{(5S)-5-[(ethanethioylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-fluorobenzoate | C17H21FN2O4S | 详情 | 详情 | |
| (V) | 58769 | 4-{(5S)-5-[(ethanethioylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-fluorobenzoic acid | C13H13FN2O4S | 详情 | 详情 | |
| (VI) | 58770 | 2,3,4,5,6-pentafluorophenyl 4-{(5S)-5-[(ethanethioylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-fluorobenzoate | C19H12F6N2O4S | 详情 | 详情 |