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【结 构 式】 
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【分子编号】14536 【品名】2-[(1S)-1-benzyl-3-hydroxy-2-oxopropyl]-1H-isoindole-1,3(2H)-dione 【CA登记号】 |
【 分 子 式 】C18H15NO4 【 分 子 量 】309.32144 【元素组成】C 69.89% H 4.89% N 4.53% O 20.69% |
合成路线1
该中间体在本合成路线中的序号：(XXI)2) The condensation of N-phthaloyl-L-phenylalaninyl chloride (XVIII) with 1,1,2-tris(trimethylsilyloxy)ethylene (TMS) (XIX) at 90-100 C followed by acidic hydrolysis with HCl gives the acid (XX), which, without isolation, is decarboxylated, yielding 1-hydroxy-3(S)-phthalimido-4-phenyl-2-butanone (XXI). Sequential protection of the OH- group with dihydropyran, reduction of the CO group with NaBH4, mesylation of the resulting OH group with methanesulfonyl chloride and deprotection of the primary OH group gives 2(R)-(methanesulfonyloxy)-4-phenyl-3(S)-phthalimido-1-butanol (XXII). The epoxidation of (XXII) with potassium tert-butoxide yields the epoxide (XXIII), which is condensed with the decahydroisoquinoline (XI) as before, affording the protected condensation product (XXIV). The elimination of the phthalimido group of (XXIV) with methylamine and HCl gives the amino derivative (XIII), already obtained in scheme 16810301a.
| 【1】 Parkes, K.E.B.; Bushnell, D.J.; Crackett, P.H.; et al.; Studies toward the large-scale synthesis of the HIV proteinase inhibitor Ro 31-8959. J Org Chem 1994, 59, 13, 3656. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 13955 | (3S,4aS,8aS)-N-(tert-Butyl)decahydro-3-isoquinolinecarboxamide | C14H26N2O | 详情 | 详情 | |
| (XIII) | 14528 | (3S,4aS,8aS)-2-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(tert-butyl)decahydro-3-isoquinolinecarboxamide | C24H39N3O2 | 详情 | 详情 | |
| (XVIII) | 56756 | diethyl 2-[(2R)-4-chloro-2-methyl-4-oxobutyl]malonate | C12H19ClO5 | 详情 | 详情 | |
| (XIX) | 14534 | 2,2,7,7-tetramethyl-4-[(trimethylsilyl)oxy]-3,6-dioxa-2,7-disila-4-octene; 1,2-bis[(trimethylsilyl)oxy]vinyl trimethylsilyl ether; TRIS(TRIMETHYLSILYLOXY)ETHYLENE | 69097-20-7 | C11H28O3Si3 | 详情 | 详情 |
| (XX) | 14535 | (4S)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-hydroxy-3-oxo-5-phenylpentanoic acid | C19H15NO6 | 详情 | 详情 | |
| (XXI) | 14536 | 2-[(1S)-1-benzyl-3-hydroxy-2-oxopropyl]-1H-isoindole-1,3(2H)-dione | C18H15NO4 | 详情 | 详情 | |
| (XXII) | 14537 | (1R,2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-(hydroxymethyl)-3-phenylpropyl methanesulfonate | C19H19NO6S | 详情 | 详情 | |
| (XXIII) | 14538 | 2-[(1S)-1-[(2S)oxiranyl]-2-phenylethyl]-1H-isoindole-1,3(2H)-dione | C18H15NO3 | 详情 | 详情 | |
| (XXIV) | 14539 | (3S,4aS,8aS)-N-(tert-butyl)-2-[(2R,3S)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-hydroxy-4-phenylbutyl]decahydro-3-isoquinolinecarboxamide | C32H41N3O4 | 详情 | 详情 |