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【结 构 式】 
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【分子编号】38790 【品名】methyl (2S)-2-[([(4R)-3-[(2S,3S)-2-amino-3-methylpentyl]-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl)amino]-4-(methylsulfanyl)butanoate 【CA登记号】 |
【 分 子 式 】C18H35N3O3S2 【 分 子 量 】405.62632 【元素组成】C 53.3% H 8.7% N 10.36% O 11.83% S 15.81% |
合成路线1
该中间体在本合成路线中的序号：(X)L-5,5-Dimethylthiazolidine-4-carboxylic acid (I) was protected as the N-Boc derivative (II) by treatment with Boc2O and subsequently coupled with L-methionine methyl ester (III) employing EDC and HOBt. The resulting Boc-dipeptide (IV) was then deprotected with trifluoroacetic acid to give (V). On the other hand, Boc-isoleucine (VI) was converted to the N-methoxy amide (VII) by condensation with N,O-dimethylhydroxylamine in the presence of O-benzotriazolyl tetramethyluronium hexafluorophosphate. Reduction of (VII) with LiAlH4 in cold Et2O produced the corresponding aldehyde (VIII). Reductive condensation of thiazolidine (V) with aldehyde (VIII) yielded adduct (IX). The Boc group of (IX) was then deprotected with trifluoroacetic acid to give (X).
| 【1】 Dong, Z.X.; Kim, S.H. (Biomeasure Inc.); Inhibitors of prenyl transferases. WO 9800409 . |
| 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) | 34776 | (4R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid | 72778-00-8 | C6H11NO2S | 详情 | 详情 |
| (II) | 34777 | (4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid | C11H19NO4S | 详情 | 详情 | |
| (III) | 17950 | D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride | 21691-49-6 | C6H13NO2S | 详情 | 详情 |
| (IV) | 38786 | tert-butyl (4R)-4-([[(1S)-1-(methoxycarbonyl)-3-(methylsulfanyl)propyl]amino]carbonyl)-5,5-dimethyl-1,3-thiazolidine-3-carboxylate | C17H30N2O5S2 | 详情 | 详情 | |
| (V) | 38787 | methyl (2S)-2-([[(4R)-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl]amino)-4-(methylsulfanyl)butanoate | C12H22N2O3S2 | 详情 | 详情 | |
| (VI) | 30009 | (2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid | 13139-16-7 | C11H21NO4 | 详情 | 详情 |
| (VII) | 38788 | tert-butyl (1S,2S)-1-[[methoxy(methyl)amino]carbonyl]-2-methylbutylcarbamate | 3350-19-4 | C13H26N2O4 | 详情 | 详情 |
| (VIII) | 34733 | tert-butyl (1S,2S)-1-formyl-2-methylbutylcarbamate | C11H21NO3 | 详情 | 详情 | |
| (IX) | 38789 | methyl (2S)-2-[[((4R)-3-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentyl]-5,5-dimethyl-1,3-thiazolidin-4-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate | C23H43N3O5S2 | 详情 | 详情 | |
| (X) | 38790 | methyl (2S)-2-[([(4R)-3-[(2S,3S)-2-amino-3-methylpentyl]-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl)amino]-4-(methylsulfanyl)butanoate | C18H35N3O3S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Protected L-cysteine (XI) was converted to aldehyde (XIII) via formation of the corresponding N-methoxy amide (XII) and further reduction with LiAlH4. Reductive condensation of amine (X) with aldehyde (XIII) in the presence of NaBH4CN furnished (XIV). The Boc group of (XIV) was finally deprotected by treatment with trifluoroacetic acid in the presence of triethylsilane.
| 【1】 Dong, Z.X.; Kim, S.H. (Biomeasure Inc.); Inhibitors of prenyl transferases. WO 9800409 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 38790 | methyl (2S)-2-[([(4R)-3-[(2S,3S)-2-amino-3-methylpentyl]-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl)amino]-4-(methylsulfanyl)butanoate | C18H35N3O3S2 | 详情 | 详情 | |
| (XI) | 38791 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propionic acid | 21947-98-8 | C27H29NO4S | 详情 | 详情 |
| (XII) | 38792 | tert-butyl (1R)-2-[methoxy(methyl)amino]-2-oxo-1-[(tritylsulfanyl)methyl]ethylcarbamate | C29H34N2O4S | 详情 | 详情 | |
| (XIII) | 17953 | tert-butyl (1R)-1-formyl-2-(tritylsulfanyl)ethylcarbamate | C27H29NO3S | 详情 | 详情 | |
| (XIV) | 38793 | methyl (2S)-2-([[(4R)-3-((2S,3S)-2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propyl]amino]-3-methylpentyl)-5,5-dimethyl-1,3-thiazolidin-4-yl]carbonyl]amino)-4-(methylsulfanyl)butanoate | C45H64N4O5S3 | 详情 | 详情 |