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【结 构 式】 
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【分子编号】51004 【品名】methyl (2S)-3-amino-2-[[(4-[4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]propanoate 【CA登记号】 |
【 分 子 式 】C26H36N4O8S 【 分 子 量 】564.66 【元素组成】C 55.31% H 6.43% N 9.92% O 22.67% S 5.68% |
合成路线1
该中间体在本合成路线中的序号：(X)3,5-Dimethylphenol (I) was alkylated with ethyl 4-bromobutyrate (II) to provide the (dimethylphenoxy)butyrate ester (III), which was hydrolyzed under basic conditions to yield acid (IV). This was sulfonated with chlorosulfonic acid, and the resultant sulfonyl chloride (V) was condensed with Boc-diaminopropanoic acid (VI) to afford sulfonamide (VII). Coupling of (VII) with mono-benzyloxycarbonyl ethylenediamine (VIII) furnished amide (IX). Then, acid cleavage of the Boc protecting group of (IX) provided amine (X).
| 【1】 Cheesman, E.H.; et al.; Nonpeptide vitronectin antagonists labeles with in-111 for imaging tumors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 88. |
| 【2】 Rajopadhye, M.; Harris, T.D.; Cheesman, E.H. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. WO 0035488 . |
| 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) | 46786 | 3,5-dimethylphenol | 108-68-9 | C8H10O | 详情 | 详情 |
| (II) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (III) | 50998 | ethyl 4-(3,5-dimethylphenoxy)butanoate | C14H20O3 | 详情 | 详情 | |
| (IV) | 50999 | 4-(3,5-dimethylphenoxy)butyric acid | C12H16O3 | 详情 | 详情 | |
| (V) | 51000 | 4-[4-(chlorosulfonyl)-3,5-dimethylphenoxy]butyric acid | C12H15ClO5S | 详情 | 详情 | |
| (VI) | 25095 | methyl (2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate | C9H18N2O4 | 详情 | 详情 | |
| (VII) | 51001 | 4-(4-[[((1S)-1-[[(tert-butoxycarbonyl)amino]methyl]-2-methoxy-2-oxoethyl)amino]sulfonyl]-3,5-dimethylphenoxy)butyric acid | C21H32N2O9S | 详情 | 详情 | |
| (VIII) | 51002 | benzyl 2-aminoethylcarbamate | C10H14N2O2 | 详情 | 详情 | |
| (IX) | 51003 | methyl (2S)-2-[[(4-[4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]-3-[(tert-butoxycarbonyl)amino]propanoate | C31H44N4O10S | 详情 | 详情 | |
| (X) | 51004 | methyl (2S)-3-amino-2-[[(4-[4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]propanoate | C26H36N4O8S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Amine (X) was coupled with carboxylic acid (XI) to afford the corresponding amide (XII) (1,2). Basic hydrolysis of the ester group of (XII) gave acid (XIII), and subsequent cleavage of the remaining protecting groups of (XIII) with trifluoroacetic acid in the presence of triethylsilane furnished (XIV).
| 【1】 Rajopadhye, M.; Harris, T.D.; Cheesman, E.H. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. WO 0035488 . |
| 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) | 51004 | methyl (2S)-3-amino-2-[[(4-[4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]propanoate | C26H36N4O8S | 详情 | 详情 | |
| (XI) | 51005 | 1-[3-[(1-trityl-1H-imidazol-2-yl)amino]propyl]-1H-indazole-5-carboxylic acid | C33H29N5O2 | 详情 | 详情 | |
| (XII) | 51006 | methyl (2S)-2-[[(4-[4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]-3-[[(1-[3-[(1-trityl-1H-imidazol-2-yl)amino]propyl]-1H-indazol-5-yl)carbonyl]amino]propanoate | C59H63N9O9S | 详情 | 详情 | |
| (XIII) | 51007 | (2S)-2-[[(4-[4-[(2-[[(benzyloxy)carbonyl]amino]ethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]-3-[[(1-[3-[(1-trityl-1H-imidazol-2-yl)amino]propyl]-1H-indazol-5-yl)carbonyl]amino]propionic acid | C58H61N9O9S | 详情 | 详情 | |
| (XIV) | 51008 | (2S)-2-[[(4-[4-[(2-aminoethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid | C31H41N9O7S | 详情 | 详情 |