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【结 构 式】 
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【分子编号】23496 【品名】(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propionic acid 【CA登记号】 |
【 分 子 式 】C14H18ClNO4 【 分 子 量 】299.75396 【元素组成】C 56.1% H 6.05% Cl 11.83% N 4.67% O 21.35% |
与该中间体有关的原料药合成路线共 3 条
合成路线1
该中间体在本合成路线中的序号：(XVIII)The synthesis of ganirelix was performed using usual solid-state peptide synthesis with a The following amino acids were added successively to intermediate (XIII): N-Boc-O-benzyl-L-serine (XIV), Boc-(3-pyridyl)-D-alanine (XVI) and Boc-4-chloro-D-phenylalanine (XVIII), yielding successively the peptide resins (XV), (XVII) and (XIX).
| 【1】 Robinson, J.3rd; Morgans, D.J.; Bingenheimer, W.; Arzeno, H.B.; Temporary serine protection in solid phase synthesis of LH-RH analogs. Int J Pept Protein Res 1993, 41, 4, 342. |
| 【2】 Castaner, J.; Leeson, P.; Rabasseda, X.; Ganirelix Acetate. Drugs Fut 1999, 24, 4, 393. |
| 【3】 Nestor, J.J. Jr.; Vickery, B.H. (Syntex (USA), Inc.); Nonapeptide and decapeptide analogs of LHRH as LHRH antagonists. EP 0277829; JP 1988201199; US 4801577 . |
| 【4】 Vickery, B.H. (Syntex (USA), Inc.); LHRH antagonist analogs and 19-nor-progestational steroids for therapy. EP 0301850 . |
| 【5】 Nestor, J.J. Jr.; McClure, N.L. (Syntex (USA), Inc.); Temporary minimal protection synthesis of LH-RH analogs. EP 0443532; JP 1992211096; US 5212288 . |
| 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) | 23491 | (2R)-2-[([(2S)-1-[(2S,5S,8R,11S)-2,8-bis(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-11-(4-hydroxybenzyl)-5-isobutyl-15,15-dimethyl-4,7,10,13-tetraoxo-14-oxa-3,6,9,12-tetraazahexadec-1-anoyl]pyrrolidinyl]carbonyl)amino]propionic acid | C50H86N12O10 | 详情 | 详情 | |
| (XIV) | 16886 | (2S)-3-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]propionic acid; N-alpha-t-BOC-o-benzyl-L-serine | 23680-31-1 | C15H21NO5 | 详情 | 详情 |
| (XV) | 23493 | (2R)-2-[([(2S)-1-[(2S,5S,8R,11S,14S)-14-[(benzyloxy)methyl]-2,8-bis(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-11-(4-hydroxybenzyl)-5-isobutyl-18,18-dimethyl-4,7,10,13,16-pentaoxo-17-oxa-3,6,9,12,15-pentaazanonadec-1-anoyl]pyrrolidinyl]carbonyl | C60H97N13O12 | 详情 | 详情 | |
| (XVI) | 23494 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(3-pyridinyl)propionic acid | C13H18N2O4 | 详情 | 详情 | |
| (XVII) | 23495 | (2R)-2-[([(2S)-1-[(2S,5S,8R,11S,14S,17R)-2,8-bis(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-11-(4-hydroxybenzyl)-14-(hydroxymethyl)-5-isobutyl-21,21-dimethyl-4,7,10,13,16,19-hexaoxo-17-(3-pyridinylmethyl)-20-oxa-3,6,9,12,15,18-hexaazadocos-1-an | C61H99N15O13 | 详情 | 详情 | |
| (XVIII) | 23496 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propionic acid | C14H18ClNO4 | 详情 | 详情 | |
| (XIX) | 23497 | (2R)-2-[([(2S)-1-[(2S,5S,8R,11S,14S,17R,20R)-20-(4-chlorobenzyl)-2,8-bis(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-11-(4-hydroxybenzyl)-14-(hydroxymethyl)-5-isobutyl-24,24-dimethyl-4,7,10,13,16,19,22-heptaoxo-17-(3-pyridinylmethyl)-23-oxa-3,6, | C70H107ClN16O14 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXII)Peptide (XIX) was sequentially coupled with N-alpha-Boc-D-(3-pyridyl)alanine (XX) and N-Boc-D-(4-chlorophenyl)alanine (XXII) to furnish, after the corresponding deprotection cycles with TFA, the resins (XXI) and (XXIII), respectively.
| 【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 |
|---|---|---|---|---|---|---|
| (XIX) | 46757 | benzyl (5S,8S,11R,14S,17S)-17-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4-pyrimidinyl]carbonyl]amino)benzyl]-8-isobutyl-7,10,13,16-tetraoxo-20-phenyl-19-oxa-6,9,12,15-tetraazaicos-1-yl(isopropyl)carbamate | C69H94N14O14 | 详情 | 详情 | |
| (XX) | 23494 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(3-pyridinyl)propionic acid | C13H18N2O4 | 详情 | 详情 | |
| (XXI) | 46760 | benzyl (5S,8S,11R,14S,17S,20R)-20-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4-pyrimidinyl]carbonyl]amino)benzyl]-8-isobutyl-7,10,13,16,19-pentaoxo-21-(3-pyridinyl)-6,9,12,15,18-pentaazahenicos-1-yl(isopropyl)carbamate | C77H102N16O15 | 详情 | 详情 | |
| (XXII) | 23496 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propionic acid | C14H18ClNO4 | 详情 | 详情 | |
| (XXIII) | 46759 | benzyl (5S,8S,11R,14S,17S,20R,23R)-23-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11-(4-[[(tert-butylamino)carbonyl]amino]benzyl)-24-(4-chlorophenyl)-14-[4-([[(4R)-2,6-dioxohexahydro-4-pyrimidinyl]carbonyl]amino)benzyl]-8-isobutyl-7,10,13,16,19,22-hexaoxo-20-(3-pyridinylmethyl)-6,9,12,15,18,21-hexaazatetracos-1-yl(isopropyl)carbamate | C86H110ClN17O16 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XVII)Coupling/deprotection cycles with N-Boc-D-(3-pyridyl)alanine (XV), N-Boc-D-4-chlorophenylalanine (XVII) and N-Boc-D-(2-naphthyl)alanine (XIX) furnished the peptide resins (XVI), (XVIII) and (XX).
| 【1】 Rivier, J.E.; et al.; Gonadotropin-releasing hormone antagonists: Novel members of the azaline B family. J Med Chem 1995, 38, 14, 2649. |
| 【2】 Rivier, J.E.F.; Porter, J.S.; Hoeger, C.A.; Jiang, G.; Rivier, C.L. (The Salk Institute for Biological Studies); GnRH antagonists. EP 0804471; JP 1998500397; US 5506207; WO 9525741 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 51381 | benzyl (5S,8S,11R,14S,17S)-17-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-11,14-bis(4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]benzyl)-8-isobutyl-7,10,13,16-tetraoxo-20-phenyl-19-oxa-6,9,12,15-tetraazaicos-1-yl(isopropyl)carbamate | C89H101N11O14 | 详情 | 详情 | |
| (XV) | 23494 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(3-pyridinyl)propionic acid | C13H18N2O4 | 详情 | 详情 | |
| (XVI) | 51382 | benzyl (5S,8S,11R,14S,17S,20R)-20-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-11,14-bis(4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]benzyl)-8-isobutyl-7,10,13,16,19-pentaoxo-21-(3-pyridinyl)-6,9,12,15,18-pentaazahenicos-1-yl(isopropyl)carbamate | C97H109N13O15 | 详情 | 详情 | |
| (XVII) | 23496 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propionic acid | C14H18ClNO4 | 详情 | 详情 | |
| (XVIII) | 51583 | 4-(2-ethyl-5-nitro-2,3-dihydro-1H-inden-2-yl)-1H-imidazole | C14H15N3O2 | 详情 | 详情 | |
| (XIX) | 23498 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-naphthyl)propionic acid | C18H21NO4 | 详情 | 详情 | |
| (XX) | 51384 | benzyl (5S,8S,11R,14S,17S,20R,23R,26R)-26-amino-5-[[(2S)-2-([[(1R)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]carbonyl]-17-[(benzyloxy)methyl]-23-(4-chlorobenzyl)-11,14-bis(4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]benzyl)-8-isobutyl-27-(2-naphthyl)-7,10,13,16,19,22,25-heptaoxo-20-(3-pyridinylmethyl)-6,9,12,15,18,21,24-heptaazaheptacos-1-yl(isopropyl)carbamate | C119H128ClN15O17 | 详情 | 详情 |
Extended Information