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【结 构 式】 
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【分子编号】38707 【品名】tert-butyl 4-[2-[(2S)-4-hydroxy-2-isopropyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]ethyl]phenylcarbamate 【CA登记号】 |
【 分 子 式 】C21H29NO5 【 分 子 量 】375.465 【元素组成】C 67.18% H 7.79% N 3.73% O 21.31% |
合成路线1
该中间体在本合成路线中的序号：(VII)The condensation of 5-[4-(tert-butoxycarbonylamino)phenyl]-2-methyl-3-pentanone (I) with tert-butylacetate (II) by means of LDA in THF, followed by hydrolysis of the ether with LiOH gives the racemic 3-hydroxypentanoic acid (III), which is submitted to optical resolution with (S)-alpha-methylbenzylamine affording the (S)-enantiomer (IV). The condensation of (IV) with the magnesium salt of monoethyl malonate (V) affords the beta-keto ester (VI), which is cyclized by means of NaOH to provide the dihydropyrone (VII). The condensation of (VII) with thiosulfonate (VIII) by means of K2CO3 in DMF yields the expected thioether (IX), which is finally treated with NaOH in DMSO/water to eliminate the tert-butoxycarbonyl protecting group.
| 【1】 Domagala, J.M.; Boyer, F.E.; Vara Prasad, J.V.N.; et al.; Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: A lead HIV protease inhibitor. Bioorg Med Chem 1999, 7, 12, 2775. |
| 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) | 38701 | tert-butyl 4-(4-methyl-3-oxopentyl)phenylcarbamate | C17H25NO3 | 详情 | 详情 | |
| (II) | 38702 | tert-butyl propionate | 20487-40-5 | C7H14O2 | 详情 | 详情 |
| (III) | 38703 | 3-[4-[(tert-butoxycarbonyl)amino]phenethyl]-3-hydroxy-4-methylpentanoic acid | C19H29NO5 | 详情 | 详情 | |
| (IV) | 38704 | (3S)-3-[4-[(tert-butoxycarbonyl)amino]phenethyl]-3-hydroxy-4-methylpentanoic acid | C19H29NO5 | 详情 | 详情 | |
| (V) | 38705 | Mg | 详情 | 详情 | ||
| (VI) | 38706 | ethyl (5S)-5-[4-[(tert-butoxycarbonyl)amino]phenethyl]-5-hydroxy-6-methyl-3-oxoheptanoate | C23H35NO6 | 详情 | 详情 | |
| (VII) | 38707 | tert-butyl 4-[2-[(2S)-4-hydroxy-2-isopropyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]ethyl]phenylcarbamate | C21H29NO5 | 详情 | 详情 | |
| (VIII) | 38708 | S-[2-(tert-butyl)-4-(hydroxymethyl)-5-methylphenyl] 4-methylbenzenesulfonothioate | C19H24O3S2 | 详情 | 详情 | |
| (IX) | 38709 | tert-butyl 4-[2-((2S)-5-[[2-(tert-butyl)-4-(hydroxymethyl)-5-methylphenyl]sulfanyl]-4-hydroxy-2-isopropyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)ethyl]phenylcarbamate | C33H45NO6S | 详情 | 详情 |