(2R)-2-([[(2S)-1-((2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】23485

【品名】(2R)-2-([[(2S)-1-((2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid

【CA登记号】

【分子式】C₂₄H₄₄N₆O₆

【分子量】512.6502

【元素组成】C 56.23% H 8.65% N 16.39% O 18.73%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VII)

The synthesis of ganirelix was performed using usual solid-state peptide synthesis with a Beckman 990 or a 5.0 L Vega 296 automated solid-phase peptide synthesizer. The synthesis was initiated by condensation of chloromethylated polystyrene/divinylbenzene resin (Merrifieled resin) (II) with Boc-D-alanine (I) by means of cesium carbonate, giving Boc-D-ala-RESIN (III), which was submitted to successive cycles of deprotection with TFA or HCl and addition of a new protected amino acid by means of DCC or HOBt. The following amino acids were added successively: Boc-L-proline (IV), Nalpha-Boc-Nomega,N'omega-diethyl-L-homoarginine (VI), Boc-L-leucine (VIII), Nalpha-Boc-Nomega,N'omega-diethyl-D-homoarginine (X) and Boc-L-tyrosine (XII), yielding successively the peptide resins (V), (VII), (IX), (XI) and (XIII).

参考文献中间体

合成目标

【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.; McClure, N.L. (Syntex (USA), Inc.); Temporary minimal protection synthesis of LH-RH analogs. EP 0443532; JP 1992211096; US 5212288 .
【4】 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 .
【5】 Vickery, B.H. (Syntex (USA), Inc.); LHRH antagonist analogs and 19-nor-progestational steroids for therapy. EP 0301850 .

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)	15859	Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid	7764-95-6	C₈H₁₅NO₄	详情	详情
(IV)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(V)	23483	(2R)-2-([[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]carbonyl]amino)propionic acid		C₁₃H₂₂N₂O₅	详情	详情
(VI)	23484	(2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoic acid		C₁₆H₃₂N₄O₄	详情	详情
(VII)	23485	(2R)-2-([[(2S)-1-((2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid		C₂₄H₄₄N₆O₆	详情	详情
(VIII)	23663	(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine		C₁₁H₂₁NO₄	详情	详情
(IX)	23487	(2R)-2-([[(2S)-1-((2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoyl]amino)-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid		C₃₀H₅₅N₇O₇	详情	详情
(X)	23488	(2R)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoic acid		C₁₆H₃₂N₄O₄	详情	详情
(XI)	23489	(2R)-2-[([(2S)-1-[(2S,5S,8R,14E)-8-[(tert-butoxycarbonyl)amino]-14-(ethylamino)-2-(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-5-isobutyl-4,7-dioxo-3,6,13,15-tetraaza-14-heptadecen-1-anoyl]pyrrolidinyl]carbonyl)amino]propionic acid		C₄₁H₇₇N₁₁O₈	详情	详情
(XII)	23490	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propionic acid		C₁₄H₁₉NO₅	详情	详情
(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

Extended Information