tert-butyl (1S)-2-hydroxy-1-{[(3S)-2-oxopyrrolidinyl]methyl}ethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】55039

【品名】tert-butyl (1S)-2-hydroxy-1-{[(3S)-2-oxopyrrolidinyl]methyl}ethylcarbamate

【CA登记号】

【分子式】C₁₂H₂₂N₂O₄

【分子量】258.31776

【元素组成】C 55.8% H 8.58% N 10.84% O 24.77%

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 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

合成路线2

该中间体在本合成路线中的序号：(XII)

Treatment of the Boc-protected aminoalcohol (XII) with trifluoroacetic acid furnishes (XIII). This is then coupled with acid (XI) in the presence of HATU to afford the amide alcohol (XIV). Oxidation of (XIV) with the Dess-Martin periodinane (DMP) reagent gives rise to aldehyde (XV). Finally, Wittig condensation of aldehyde (XV) with isopropoxycarbonylmethylene triphenylphosphorane provides the target unsaturated ester. (1,2)

参考文献中间体

合成目标

【1】 Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors: 6. Structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics. J Med Chem 2002, 45, 8, 1607.
【2】 Dragovich, P.S.; Prins, T.J.; Zhou, R.; Johnson, T.O. Jr. (Agouron Pharmaceuticals, Inc.); Antipicornaviral cpds. and compsns., their pharmaceutical uses, and material for their synthesis. JP 2003515591; US 2001047006; US 6514997; WO 0140189 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	63734	3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoic acid	C₁₉H₁₅F₂N₃O₅	详情	详情
(XII)	55039	tert-butyl (1S)-2-hydroxy-1-{[(3S)-2-oxopyrrolidinyl]methyl}ethylcarbamate	C₁₂H₂₂N₂O₄	详情	详情
(XIII)	63735	3-(2-amino-3-hydroxypropyl)-2-pyrrolidinone	C₇H₁₄N₂O₂	详情	详情
(XIV)	63736	N-{1-[1-[(3,4-difluorophenyl)methyl]-2-({2-hydroxy-1-[(2-oxo-3-pyrrolidinyl)methyl]ethyl}amino)-2-oxoethyl]-2-oxo-1,2-dihydro-3-pyridinyl}-5-methyl-3-isoxazolecarboxamide	C₂₆H₂₇F₂N₅O₆	详情	详情
(XV)	63737	N-[1-(1-[(3,4-difluorophenyl)methyl]-2-{[1-formyl-2-(2-oxo-3-pyrrolidinyl)ethyl]amino}-2-oxoethyl)-2-oxo-1,2-dihydro-3-pyridinyl]-5-methyl-3-isoxazolecarboxamide	C₂₆H₂₅F₂N₅O₆	详情	详情

Extended Information