ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-5-[(3S)-2-oxopyrrolidinyl]-2-pentenoate -Drug Synthesis Database

【结构式】

【分子编号】55041

【品名】ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-5-[(3S)-2-oxopyrrolidinyl]-2-pentenoate

【CA登记号】

【分子式】C₁₆H₂₆N₂O₅

【分子量】326.39292

【元素组成】C 58.88% H 8.03% N 8.58% O 24.51%

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：(IX)

The alkylation of dimethyl L-glutamate (I) with 2-bromoacetonitrile (II) by means of LiHMDS in THF gives stereoselectively the cyanomethyl derivative (III), which is reduced with H2 over PtO2 in methanol/CHCl3 to yield the corresponding 2-aminoethyl derivative (IV). The cyclization of (IV) by means of Na2CO3 in the same solvent affords the pyrrolidinone (V), whose ester group is reduced with NaBH4 in methanol/THF to provide the propanol derivative (VI). The oxidation of (VI) with SO3/pyridine and DIEA in DMSO/dichloromethane gives the aldehyde (VII), which is finally condensed with ethyl 2-bromoacetate (VIII) by means of Et3P in dichloromethane to yield the chiral 4-(tert-butoxycarbonyl)-5-(2-oxopyrrolidin-3-yl)-2-pentanoic acid ethyl ester (IX), the desired target key intermediate.

参考文献中间体

合成目标

【1】 Tian, Q.; et al.; An efficient synthesis of a key intermediate for the preparation of the rhinovirus protease inhibitor AG7088 via asymmetric dianionic cyanomethylation of N-Boc-L-(+)-glutamic acid dimethyl ester. Tetrahedron Lett 2001, 42, 39, 6807.

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)	55035	dimethyl (2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate		C₁₂H₂₁NO₆	详情	详情
(II)	31883	2-bromoacetonitrile	590-17-0	C₂H₂BrN	详情	详情
(III)	55036	dimethyl (2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-(cyanomethyl)pentanedioate		C₁₄H₂₂N₂O₆	详情	详情
(IV)	55037	dimethyl (2S,4S)-2-(2-aminoethyl)-4-[(tert-butoxycarbonyl)amino]pentanedioate		C₁₄H₂₆N₂O₆	详情	详情
(V)	55038	methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[(3S)-2-oxopyrrolidinyl]propanoate		C₁₃H₂₂N₂O₅	详情	详情
(VI)	55039	tert-butyl (1S)-2-hydroxy-1-{[(3S)-2-oxopyrrolidinyl]methyl}ethylcarbamate		C₁₂H₂₂N₂O₄	详情	详情
(VII)	55040	tert-butyl (1S)-1-formyl-2-[(3S)-2-oxopyrrolidinyl]ethylcarbamate		C₁₂H₂₀N₂O₄	详情	详情
(VIII)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(IX)	55041	ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-5-[(3S)-2-oxopyrrolidinyl]-2-pentenoate		C₁₆H₂₆N₂O₅	详情	详情

Extended Information