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【结 构 式】 
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【药物名称】A-160621 【化学名称】N-(2-Isopropylthiazol-4-ylmethoxycarbonyl)-L-valine N-[3-[4-(1,3-benzodioxol-5-ylmethyl)-2(S)-(tert-butylcarbamoyl)piperazin-1-yl]-1(S)-benzyl-2(R)-hydroxypropyl]amide 【CA登记号】 【 分 子 式 】C40H56N6O7S 【 分 子 量 】764.99232 |
【开发单位】Abbott (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, HIV Protease Inhibitors |
合成路线1
Intermediate (III) was prepared by condensation of epoxide (I) with piperazine (II). After removal of the carbobenzoxy protecting group of (III) by catalytic hydrogenation, the resulting amine (IV) was coupled to the valine derivative (V) using EDC to afford amide (VI). Subsequent cleavage of the Boc protecting group of (VI) under acidic conditions gave (VII), which was finally alkylated with the benzodioxolylmethyl halide (VIII) to provide the target compound.
| 【1】 Chen, X.; Kempf, D.J.; Sham, H.L.; Green, B.E.; Molla, A.; Korneyeva, M.; Vasavanonda, S.; Wideburg, N.E.; Saldivar, A.; Marsh, K.C.; McDonald, E.; Norbeck, D.W.; Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3 ligands. Bioorg Med Chem Lett 1998, 8, 24, 3531. |
| 【2】 Chen, X.; Mohammadi, F.; Norbeck, D.W.; Kempf, D.J. (Abbott Laboratories Inc.); Retroviral protease inhibiting cpds.. WO 9959994 . |
| 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) | 14522 | benzyl N-[(1S)-1-[(2S)oxiranyl]-2-phenylethyl]carbamate | C18H19NO3 | 详情 | 详情 | |
| (II) | 16422 | methyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate | C8H11NO2 | 详情 | 详情 | |
| (III) | 30251 | tert-butyl (3S)-4-((2R,3S)-3-[[(benzyloxy)carbonyl]amino]-2-hydroxy-4-phenylbutyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C32H46N4O6 | 详情 | 详情 | |
| (IV) | 30252 | tert-butyl (3S)-4-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C24H40N4O4 | 详情 | 详情 | |
| (V) | 30255 | (2S)-2-([[(2-isopropyl-1,3-thiazol-4-yl)methoxy]carbonyl]amino)-3-methylbutyric acid | C13H20N2O4S | 详情 | 详情 | |
| (VI) | 30253 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]-4-((2R,3S)-2-hydroxy-3-[[(2S)-2-([[(2-isopropyl-1,3-thiazol-4-yl)methoxy]carbonyl]amino)-3-methylbutanoyl]amino]-4-phenylbutyl)-1-piperazinecarboxylate | C37H58N6O7S | 详情 | 详情 | |
| (VII) | 30254 | (2-isopropyl-1,3-thiazol-4-yl)methyl (1S)-1-[[((1S,2R)-1-benzyl-3-[(2S)-2-[(tert-butylamino)carbonyl]piperazinyl]-2-hydroxypropyl)amino]carbonyl]-2-methylpropylcarbamate | C32H50N6O5S | 详情 | 详情 | |
| (VIII) | 28617 | 5-(chloromethyl)-1,3-benzodioxole | C8H7ClO2 | 详情 | 详情 |