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【结 构 式】 
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【分子编号】29585 【品名】benzyl (1S,3R,4R)-3-(benzyloxy)-1-formyl-7-azabicyclo[2.2.1]heptane-7-carboxylate 【CA登记号】 |
【 分 子 式 】C22H23NO4 【 分 子 量 】365.42896 【元素组成】C 72.31% H 6.34% N 3.83% O 17.51% |
合成路线1
该中间体在本合成路线中的序号：(IV)The chiral bicyclic alcohol (I) was converted to the benzyl ether (II) using benzyl bromide and NaH. Subsequent reduction of the ester group of (III) with LiBH4 provided primary alcohol (III), and further Swern oxidation yielded aldehyde (IV). Pinacol coupling of (IV) with D-phenylalaninal (V) by means of VCl3 - (THF)3 and Zn furnished diol (VI) with 85% diastereoselectivity. This was protected as the acetonide (VIII) upon treatment with 2,2-dimethoxypropane (VII) and camphorsulfonic acid. Selective removal of the two N-benzyloxycarbonyl groups of (VIII) by hydrogenation in the presence of Pd/C and NH3 gave diamine (IX), which was cyclized to the urea (X) employing carbonyldiimidazole and pyridine.
| 【1】 Han, W.; Pelletier, J.C.; Hodge, C.N.; Tricyclic ureas: A new class of HIV-1 protease inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3615. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| (I) | 29582 | 7-benzyl 1-(tert-butyl) (1S,3R,4R)-3-hydroxy-7-azabicyclo[2.2.1]heptane-1,7-dicarboxylate | C19H25NO5 | 详情 | 详情 | |
| (II) | 29583 | 7-benzyl 1-(tert-butyl) (1S,3R,4R)-3-(benzyloxy)-7-azabicyclo[2.2.1]heptane-1,7-dicarboxylate | C26H31NO5 | 详情 | 详情 | |
| (III) | 29584 | benzyl (1S,3R,4R)-3-(benzyloxy)-1-(hydroxymethyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate | C22H25NO4 | 详情 | 详情 | |
| (IV) | 29585 | benzyl (1S,3R,4R)-3-(benzyloxy)-1-formyl-7-azabicyclo[2.2.1]heptane-7-carboxylate | C22H23NO4 | 详情 | 详情 | |
| (V) | 27884 | benzyl (1R)-1-benzyl-2-oxoethylcarbamate | C17H17NO3 | 详情 | 详情 | |
| (VI) | 29586 | benzyl (1S,3R,4R)-3-(benzyloxy)-1-((1R,2R,3R)-3-[[(benzyloxy)carbonyl]amino]-1,2-dihydroxy-4-phenylbutyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate | C39H42N2O7 | 详情 | 详情 | |
| (VII) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (VIII) | 29587 | benzyl (1S,3R,4R)-3-(benzyloxy)-1-[(4R,5R)-5-((1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-7-azabicyclo[2.2.1]heptane-7-carboxylate | C42H46N2O7 | 详情 | 详情 | |
| (IX) | 29588 | (1R)-1-[(4R,5R)-5-[(3R,4R)-3-(benzyloxy)-7-azabicyclo[2.2.1]hept-1-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethylamine; (1R)-1-[(4R,5R)-5-[(3R,4R)-3-(benzyloxy)-7-azabicyclo[2.2.1]hept-1-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenyl-1-ethanamine | C26H34N2O3 | 详情 | 详情 | |
| (X) | 29589 | (1S,2R,6R,7R,11R,12R)-7-benzyl-12-(benzyloxy)-4,4-dimethyl-3,5-dioxa-8,10-diazatetracyclo[9.2.2.0(1,10).0(2,6)]pentadecan-9-one | C27H32N2O4 | 详情 | 详情 |