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【结 构 式】 
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【分子编号】35617 【品名】tert-butyl (2S,4R)-2-[([(1S)-1-[(benzyloxy)carbonyl]butyl]amino)carbonyl]-4-(2-naphthylmethoxy)-1-pyrrolidinecarboxylate 【CA登记号】 |
【 分 子 式 】C33H40N2O6 【 分 子 量 】560.69048 【元素组成】C 70.69% H 7.19% N 5% O 17.12% |
合成路线1
该中间体在本合成路线中的序号：(VII)Alkylation of N-Boc-4-(R)-hydroxyproline (I) with 2-(bromomethyl)-naphthalene (II) in the presence of NaH afforded the (naphthylmethyl) ether (III). N-Boc-norvaline (IV) was converted to the benzyl ester (V) by treatment with benzyl bromide and DBU. Subsequent acid cleavage of the Boc group of (V) yielded norvaline benzyl ester (VI). This was coupled with proline derivative (III) using HATU to give the protected dipeptide (VII).
| 【1】 Rancourt, J.; Tsantrizos, Y.; Simoneau, B.; Wernic, D.; Poupart, M.-A.; Llinas-Brunet, M. (Boehringer Ingelheim (Canada) Ltd.); Hepatitis C inhibitor peptides. EP 1003775; WO 9907733 . |
| 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) | 16094 | (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid | 16094 | C10H17NO5 | 详情 | 详情 |
| (II) | 35612 | 2-(bromomethyl)naphthalene | 939-26-4 | C11H9Br | 详情 | 详情 |
| (III) | 35613 | (2S,4R)-1-(tert-butoxycarbonyl)-4-(2-naphthylmethoxy)-2-pyrrolidinecarboxylic acid | C21H25NO5 | 详情 | 详情 | |
| (IV) | 35614 | (2S)-2-[(tert-butoxycarbonyl)amino]pentanoic acid | 53308-95-5 | C10H19NO4 | 详情 | 详情 |
| (V) | 35615 | benzyl (2S)-2-[(tert-butoxycarbonyl)amino]pentanoate | C17H25NO4 | 详情 | 详情 | |
| (VI) | 35616 | benzyl (2S)-2-aminopentanoate | C12H17NO2 | 详情 | 详情 | |
| (VII) | 35617 | tert-butyl (2S,4R)-2-[([(1S)-1-[(benzyloxy)carbonyl]butyl]amino)carbonyl]-4-(2-naphthylmethoxy)-1-pyrrolidinecarboxylate | C33H40N2O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)After Boc group deprotection in (VII) by means of HCl in dioxan, coupling with N-Boc-valine (VIII) provided tripeptide (IX). Further deprotection and coupling cycles with N-Boc-cyclohexylglycine (X) and N-Boc-glutamic acid benzyl ester (XII) furnished peptides (XI) and (XIII), respectively.
| 【1】 Rancourt, J.; Tsantrizos, Y.; Simoneau, B.; Wernic, D.; Poupart, M.-A.; Llinas-Brunet, M. (Boehringer Ingelheim (Canada) Ltd.); Hepatitis C inhibitor peptides. EP 1003775; WO 9907733 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 35617 | tert-butyl (2S,4R)-2-[([(1S)-1-[(benzyloxy)carbonyl]butyl]amino)carbonyl]-4-(2-naphthylmethoxy)-1-pyrrolidinecarboxylate | C33H40N2O6 | 详情 | 详情 | |
| (VIII) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (IX) | 35618 | benzyl (2S)-2-([[(2S,4R)-1-[(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]-4-(2-naphthylmethoxy)pyrrolidinyl]carbonyl]amino)pentanoate | C38H49N3O7 | 详情 | 详情 | |
| (X) | 35619 | (2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylethanoic acid | C13H23NO4 | 详情 | 详情 | |
| (XI) | 35620 | benzyl (2S)-2-([[(2S,4R)-1-[(2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylethanoyl]amino)-3-methylbutanoyl]-4-(2-naphthylmethoxy)pyrrolidinyl]carbonyl]amino)pentanoate | C46H62N4O8 | 详情 | 详情 | |
| (XII) | 25141 | (2S)-5-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid | 13574-13-5 | C17H23NO6 | 详情 | 详情 |
| (XIII) | 35621 | benzyl (4R)-5-([(1S)-2-[((1S)-1-[[(2S,4R)-2-[([(1S)-1-[(benzyloxy)carbonyl]butyl]amino)carbonyl]-4-(2-naphthylmethoxy)pyrrolidinyl]carbonyl]-2-methylpropyl)amino]-1-cyclohexyl-2-oxoethyl]amino)-4-[(tert-butoxycarbonyl)amino]-5-oxopentanoate | C58H75N5O11 | 详情 | 详情 |