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【结 构 式】

【分子编号】23494

【品名】(2R)-2-[(tert-butoxycarbonyl)amino]-3-(3-pyridinyl)propionic acid

【CA登记号】

【 分 子 式 】C13H18N2O4

【 分 子 量 】266.297

【元素组成】C 58.63% H 6.81% N 10.52% O 24.03%

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:(XVI)

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:(XX)

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:(XV)

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