4-nitrobenzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】33058

【品名】4-nitrobenzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate

【CA登记号】

【分子式】C₁₇H₁₉N₃O₈

【分子量】393.35328

【元素组成】C 51.91% H 4.87% N 10.68% O 32.54%

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：(XXVI)

Coupling of carbapenem phosphate (VIII) with thiol (XIII) using diisopropylethylamine gave rise to sulfide (XIX). Hydrogenolysis of the p-nitrobenzyl group of (XIX) with simultaneous azide reduction in the presence of Pd/C provided (XX). Treatment of p-nitrobenzyl chloroformate (XXI) with p-nitrophenol (XXII) afforded the nitrophenyl carbonate (XXIII), which was coupled with L-valine (XXIV), yielding carbamate (XXV). Activation of (XXV) with N-hydroxy succinimide and DCC then produced the succinimidyl ester (XXVI). Amine (XX) was coupled with succinimidyl ester (XXVI) to furnish amide (XXVII). The p-nitrobenzyl ester was finally removed by hydrogenation over Pd/C to provide the title compound.

参考文献中间体

合成目标

【1】 Lin, Y.-I.; et al.; Peptidic prodrugs of novel aminomethyl-THF 1beta-methylcarbapenems. Bioorg Med Chem Lett 1997, 7, 13, 1665.
【2】 Lin, Y.-I.; Bitha, P.; Sakya, S.; Strohmeyer, T.W.; Bush, K. (American Cyanamid Co.); Novel 2-thiosubstd. carbapenems. CA 2118961; EP 0617036; JP 1994321948; US 5602118 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	13224	4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	90776-59-3	C₂₉H₂₇N₂O₁₀P	详情	详情
(XIII)	33047	(2R,3R)-2-(azidomethyl)tetrahydro-3-furanthiol; (2R,3R)-2-(azidomethyl)tetrahydro-3-furanylhydrosulfide		C₅H₉N₃OS	详情	详情
(XIX)	33053	4-nitrobenzyl (4R,5S,6S)-3-[[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₂H₂₅N₅O₇S	详情	详情
(XX)	33054	(4R,5S,6S)-3-[[(2R,3R)-2-(aminomethyl)tetrahydro-3-furanyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid		C₁₅H₂₂N₂O₅S	详情	详情
(XXI)	33055	1-[[(chlorocarbonyl)oxy]methyl]-4-nitrobenzene	4457-32-3	C₈H₆ClNO₄	详情	详情
(XXII)	11236	4-Nitrophenol; p-Nitrophenol	100-02-7	C₆H₅NO₃	详情	详情
(XXIII)	33056	4-nitrobenzyl 4-nitrophenyl carbonate		C₁₄H₁₀N₂O₇	详情	详情
(XXIV)	21056	(R)-(-)-Valine; D-Valine; (R)-alpha-Aminoisovaleric acid	640-68-6	C₅H₁₁NO₂	详情	详情
(XXV)	33057	(2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butyric acid		C₁₃H₁₆N₂O₆	详情	详情
(XXVI)	33058	4-nitrobenzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate		C₁₇H₁₉N₃O₈	详情	详情
(XXVII)	33059	(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(2R,3R)-2-([[(2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butanoyl]amino]methyl)tetrahydro-3-furanyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid		C₂₈H₃₆N₄O₁₀S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

A convergent synthesis was further developed. Azide (XII) was reduced to the corresponding amine (XXVIII) employing triethyl phosphite. Hydrolysis of the thioacetate ester of (XXVIII) then gave thiol (XXIX). Coupling of (XXIX) with protected valine succinimidyl ester (XXVI) produced amide (XXX). Condensation of (XXX) with carbapenem phosphate (VIII) yielded adduct (XXXI). The p-nitrobenzyl esters were finally deprotected by catalytic hydrogenation.

参考文献中间体

合成目标

【1】 Lin, Y.I.; Li, Z.; Bitha, P.; Convergent synthesis of oral 1beta-methylcarbapenems. J Antibiot 1999, 52, 7, 643.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	13224	4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	90776-59-3	C₂₉H₂₇N₂O₁₀P	详情	详情
(XII)	33046	S-[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl] ethanethioate		C₇H₁₁N₃O₂S	详情	详情
(XXVI)	33058	4-nitrobenzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate		C₁₇H₁₉N₃O₈	详情	详情
(XXVIII)	33060	S-[(2R,3R)-2-(aminomethyl)tetrahydro-3-furanyl] ethanethioate		C₇H₁₃NO₂S	详情	详情
(XXIX)	33061	(2R,3R)-2-(aminomethyl)tetrahydro-3-furanylhydrosulfide; (2R,3R)-2-(aminomethyl)tetrahydro-3-furanthiol		C₅H₁₁NOS	详情	详情
(XXX)	33062	4-nitrobenzyl (1S)-2-methyl-1-[([[(2R,3R)-3-sulfanyltetrahydro-2-furanyl]methyl]amino)carbonyl]propylcarbamate		C₁₈H₂₅N₃O₆S	详情	详情
(XXXI)	33063	4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(2R,3R)-2-([[(2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butanoyl]amino]methyl)tetrahydro-3-furanyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₃₅H₄₁N₅O₁₂S	详情	详情

Extended Information