【结 构 式】 |
【分子编号】38756 【品名】tert-butyl (2S,4R)-2-[(tert-butylamino)carbonyl]-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C18H34N2O4S 【 分 子 量 】374.54504 【元素组成】C 57.72% H 9.15% N 7.48% O 17.09% S 8.56% |
合成路线1
该中间体在本合成路线中的序号:(II)The reaction of (2S,4R)-1-(tert-butoxycarbonyl)-N-tert-butyl-4-hydroxypiperidine-2-carboxamide (I) with MsCl and TEA gives the mesylate (II), which is treated with tetrabutylammonium bromide in refluxing THF to yield the corresponding 4-bromo derivative (III). The reaction of (III) with potassium thioacetate, followed by hydrolysis with NaOH affords the sodium thiolate (IV), which is condensed with 4-chloropyridine (V) to provide (2S,4R)-1-(tert-butoxycarbonyl)-N-tert-butyl-4-(4-pyridylsulfanyl)piperidine-2-carboxamide (VI). The deprotection of (VI) with TFA or HCl in dioxane gives intermediate (VII), which is condensed with epoxide (VIII) in refluxing ethanol to obtain the expected addition compound (IX). The deprotection of (IX) with TFA or HCl as before yields the amide (X), which is finally condensed with 2-(2,6-dimethylphenoxy)acetic acid (XI) by means of BOP and DIEA to furnish the target diamide.
【1】 Anderson, P.C.; Beaulieu, P.L.; Cameron, D.R.; et al.; 2'6'-Dimethylphenoxyacetyl: A new achiral high affinity P3-P2 ligand for peptidomimetic-based HIV protease inhibitors. J Med Chem 2000, 43, 6, 1094. |
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) | 19736 | tert-butyl (2S,4R)-2-[(tert-butylamino)carbonyl]-4-hydroxy-1-piperidinecarboxylate | C15H28N2O4 | 详情 | 详情 | |
(II) | 38756 | tert-butyl (2S,4R)-2-[(tert-butylamino)carbonyl]-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1-piperidinecarboxylate | C18H34N2O4S | 详情 | 详情 | |
(III) | 38757 | tert-butyl (2S,4S)-4-bromo-2-[(tert-butylamino)carbonyl]-1-piperidinecarboxylate | C15H27BrN2O3 | 详情 | 详情 | |
(IV) | 38762 | C15H27N2NaO3S | 详情 | 详情 | ||
(V) | 32889 | 4-chloropyridine | 7379-35-3 | C5H4ClN | 详情 | 详情 |
(VI) | 38758 | tert-butyl (2S,4R)-2-[(tert-butylamino)carbonyl]-4-(4-pyridinylsulfanyl)-1-piperidinecarboxylate | C20H31N3O3S | 详情 | 详情 | |
(VII) | 38759 | (2S,4R)-N-(tert-butyl)-4-(4-pyridinylsulfanyl)-2-piperidinecarboxamide | C15H23N3OS | 详情 | 详情 | |
(VIII) | 19730 | tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate | 98737-29-2 | C15H21NO3 | 详情 | 详情 |
(IX) | 38760 | tert-butyl (1S,2R)-1-benzyl-3-[(2S,4R)-2-[(tert-butylamino)carbonyl]-4-(4-pyridinylsulfanyl)piperidinyl]-2-hydroxypropylcarbamate | C30H44N4O4S | 详情 | 详情 | |
(X) | 38761 | (2S,4R)-1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(tert-butyl)-4-(4-pyridinylsulfanyl)-2-piperidinecarboxamide | C25H36N4O2S | 详情 | 详情 | |
(XI) | 38270 | 2-(2,6-dimethylphenoxy)acetic acid | C10H12O3 | 详情 | 详情 |