ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-7-oxo-7-(tritylamino)-2-heptenoate -Drug Synthesis Database

【结构式】

【分子编号】31048

【品名】ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-7-oxo-7-(tritylamino)-2-heptenoate

【CA登记号】

【分子式】C₃₃H₃₈N₂O₅

【分子量】542.6752

【元素组成】C 73.04% H 7.06% N 5.16% O 14.74%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

The condensation of the protected L-glutamine (I) with N,O-dimethylhydroxylamine (II) by means of isobutyl chloroformate and NMM in dichloromethane gives the methoxyamide (III), which is reduced with DIBAL in THF to the aldehyde (IV). The condensation of (IV) with phosphonate (V) by means of NaN(SiMe3)2 in THF yields the carbamoylhexenoate (VI), which is selectively deprotected with HCl in dioxane and condensed with the dipeptide (VII) by means of HOBT, NMM and EDC in dichloromethane to afford the tritylated target compound (VIII). Finally, the trityl group of (VIII) is eliminated with TFA and Et3SiH in dichloromethane.

参考文献中间体

合成目标

【1】 Dragovich, P.S.; Babine, R.E.; Webber, S.E.; et al.; Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies. J Med Chem 1998, 41, 15, 2806.

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)	31045	(2S)-2-[(tert-butoxycarbonyl)amino]-5-oxo-5-(tritylamino)pentanoic acid		C₂₉H₃₂N₂O₅	详情	详情
(II)	13361	(Methoxyamino)methane; N,O-Dimethylhydroxylamine	1117-97-1	C₂H₇NO	详情	详情
(III)	31046	tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-4-oxo-4-(tritylamino)butylcarbamate		C₃₁H₃₇N₃O₅	详情	详情
(IV)	31047	tert-butyl (1S)-1-formyl-4-oxo-4-(tritylamino)butylcarbamate		C₂₉H₃₂N₂O₄	详情	详情
(V)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(VI)	31048	ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-7-oxo-7-(tritylamino)-2-heptenoate		C₃₃H₃₈N₂O₅	详情	详情
(VII)	31052	(2S)-2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)amino]-3-phenylpropionic acid		C₂₃H₂₈N₂O₅	详情	详情
(VII)	31053	ethyl (5S,8S,11S,12E)-11-(3-amino-3-oxopropyl)-8-benzyl-5-isobutyl-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-triaza-12-tetradecen-14-oate		C₃₂H₄₂N₄O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The reaction of the protected L-glutamine (I) with N,O-dimethylhydroxylamine (II) by means of isobutyl chloroformate and NMM in dichloromethane gives the methoxyamide (III), which is reduced with DIBAL in THF yielding the glutaminal (IV). The condensation of (IV) with phosphonate (V) by means of NaN(SiMe3)2 in THF affords the carbamoylhexenoate (VI), which is deprotected with TFA and HCl and condensed with N-(tert-butoxycabonyl)-4-methyl-L-phenylalanine (VII) by means of HOBT, NMM and EDC in dichloromethane to give the dipeptide (VIII), which is finally deprotected with HCl and condensed with N-(cyclopentylsulfanylcarbonyl)-L-tert-leucine (IX) by means of HOBT as before.

参考文献中间体

合成目标

【1】 Webber, S.E.; Dragovich, P.S.; Babine, R.E.; et al.; Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure-activity studies. J Med Chem 1998, 41, 15, 2819.

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)	31045	(2S)-2-[(tert-butoxycarbonyl)amino]-5-oxo-5-(tritylamino)pentanoic acid		C₂₉H₃₂N₂O₅	详情	详情
(II)	13361	(Methoxyamino)methane; N,O-Dimethylhydroxylamine	1117-97-1	C₂H₇NO	详情	详情
(III)	31046	tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-4-oxo-4-(tritylamino)butylcarbamate		C₃₁H₃₇N₃O₅	详情	详情
(IV)	31047	tert-butyl (1S)-1-formyl-4-oxo-4-(tritylamino)butylcarbamate		C₂₉H₃₂N₂O₄	详情	详情
(V)	31048	ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-7-oxo-7-(tritylamino)-2-heptenoate		C₃₃H₃₈N₂O₅	详情	详情
(VI)	31049	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-methylphenyl)propionic acid	80102-26-7	C₁₅H₂₁NO₄	详情	详情
(VII)	31050	ethyl (E,4S)-7-amino-4-[[(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-methylphenyl)propanoyl]amino]-7-oxo-2-heptenoate		C₂₄H₃₅N₃O₆	详情	详情
(VIII)	31051	(2S)-2-[[(cyclopentylsulfanyl)carbonyl]amino]-3,3-dimethylbutyric acid		C₁₂H₂₁NO₃S	详情	详情

Extended Information