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【结 构 式】 
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【分子编号】46763 【品名】benzyl (5S,8S,11R,14S,17S,20R,23R,26R)-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-23-(4-chlorobenzyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4 【CA登记号】 |
【 分 子 式 】C101H123ClN18O18 【 分 子 量 】1912.65084 【元素组成】C 63.43% H 6.48% Cl 1.85% N 13.18% O 15.06% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)Alternatively, after coupling of the peptide resin (XIII) with alpha-Boc-L-4-(Fmoc-amino)phenylalanine (XIV), the Fmoc protecting group was not removed, yielding resin (XXVI). Subsequent coupling cycles with amino acids (XVIII), (XX), (XXII) and (XXIV) as above finally produced resin (XXVII). The Fmoc group was then deprotected by treatment with piperidine, and the resulting aniline was acylated with L-hydroorotic acid (XVI) to provide resin (XXVIII), which was finally cleaved and deprotected by treatment with HF.
| 【1】 Stalewski, J.; Galyean, R.; Jiang, G.; et al.; GnRH antagonists: A new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6. J Med Chem 2001, 44, 3, 453. |
| 【2】 Jiang, G.; Semple, G. (Ferring BV Group Holding); GnRH antagonists being modified in positions 5 and 6. WO 9846634 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 46749 | benzyl (5S)-5-[((2S)-2-[[(2R)-2-amino-3-(4-[[(tert-butylamino)carbonyl]amino]phenyl)propanoyl]amino]-4-methylpentanoyl)amino]-6-[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]-6-oxohexyl(isopropyl)carbamate | C45H69N9O8 | 详情 | 详情 | |
| (XIV) | 46753 | (2S)-3-(4-aminophenyl)-2-[(tert-butoxycarbonyl)amino]propionic acid | 55533-24-9 | C14H20N2O4 | 详情 | 详情 |
| (XVI) | 46755 | (4R)-2,6-dioxohexahydro-4-pyrimidinecarboxylic acid | C5H6N2O4 | 详情 | 详情 | |
| (XXVI) | 46761 | 9H-fluoren-9-ylmethyl 4-[(2S,5R,8S,11S)-11-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-2-[(tert-butoxycarbonyl)amino]-5-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-8-isobutyl-16-isopropyl-3,6,9,17-tetraoxo-19-phenyl-18-oxa-4,7,10,16-tetraazanonadec-1-yl]phenylcarbamate | C74H97N11O13 | 详情 | 详情 | |
| (XXVII) | 46762 | benzyl (5S,8S,11R,14S,17S,20R,23R,26R)-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-23-(4-chlorobenzyl)-14-(4-[[(9H-fluoren-9-ylmethoxy)ca | C111H129ClN16O17 | 详情 | 详情 | |
| (XXVIII) | 46763 | benzyl (5S,8S,11R,14S,17S,20R,23R,26R)-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-23-(4-chlorobenzyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4 | C101H123ClN18O18 | 详情 | 详情 |