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【结 构 式】 
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【药物名称】WHI-05 【化学名称】3'-Azido-5-bromo-5'-O-[4-methoxyphenoxy[1-(methoxycarbonyl)ethylamino]phosphoryl]-3'-deoxy-6-methoxy-5,6-dihydrothymidine 【CA登记号】 【 分 子 式 】C22H30BrN6O10P 【 分 子 量 】649.3964 |
【开发单位】Parker Hughes Institute (Originator), Paradigm Pharmaceuticals (Not Determined) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Contraceptives, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, Female Contraceptives, Vaginal Spermicides |
合成路线1
The reaction of 4-methoxyphenol (I) with POCl3 and triethylamine in ethyl ether gives the dichlorophosphate (II), which is condensed with alanine methyl ester (III) by means of triethylamine in dichloromethane yielding the amide (IV). The condensation of (IV) with azidothymidine (V) by means of N-methylimidazole (NMI) in THF affords the 5'-phosphate derivative (VI), which is finally treated with methyl hypobromite (Br2 in methanol).
| 【1】 Uckun, F.M.; Venkatachalam, T.; D'Cruz, O. (Parker Hughes Institute); AZT derivs. exhibiting spermicidal and anti-viral activity. WO 9948902 . |
| 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) | 32744 | 4-methoxyphenol | 150-76-5 | C7H8O2 | 详情 | 详情 |
| (II) | 32741 | Dichlorophosphoric acid 4-methoxyphenyl ester | C7H7Cl2O3P | 详情 | 详情 | |
| (III) | 25315 | methyl 2-aminopropanoate; Alanine, methyl ester | 7625-53-8 | C4H9NO2 | 详情 | 详情 |
| (IV) | 32742 | methyl 2-[[chloro(4-methoxyphenoxy)phosphoryl]amino]propanoate | C11H15ClNO5P | 详情 | 详情 | |
| (V) | 25317 | 1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 101703-35-9 | C10H13N5O4 | 详情 | 详情 |
| (VI) | 32743 | methyl 2-[[([(2S,3S,5R)-3-azido-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methoxy)(4-methoxyphenoxy)phosphoryl]amino]propanoate | C21H27N6O9P | 详情 | 详情 |