(2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】26289

【品名】(2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid

【CA登记号】

【分子式】C₁₃H₁₆N₂O₅

【分子量】280.28052

【元素组成】C 55.71% H 5.75% N 9.99% O 28.54%

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：(XXVIII)

Treatment of N-(benzyloxycarbonyl)-L-glutamine (XXVIII) with (trimethylsilyl)-diazomethane provided methyl ester (XXIX). Nitrile (XXX) was then obtained from (XXIX) by dehydration with cyanuryl chloride. Hydrolysis of the methyl ester of (XXX) with LiOH gave (XXXI), and hydrogenolysis of the carbobenzoxy group provided amino acid (XXXII). Alternatively, amino acid (XXXII) could be obtained by direct amide dehydration of (XXVIII) with Ac2O and pyridine, followed by transfer hydrogenolysis of the Cbz protecting group. Diazotization of amino acid (XXXII) with NaNO2 in the presence of H2SO4 then furnished (S)-2-hydroxy-4-cyanobutyric acid (XXXIII).

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of HUN-7293. J Am Chem Soc 1999, 121, 26, 6197.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	23813	2,4,6-Trichloro-s-triazine; Cyanuric chloride; Trichlorocyanidine; Tricyanogen chloride; 2,4,6-Trichloro-1,3,5-triazine	108-77-0	C₃Cl₃N₃	详情	详情
(XXVIII)	26289	(2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid		C₁₃H₁₆N₂O₅	详情	详情
(XXIX)	26290	methyl (2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoate		C₁₄H₁₈N₂O₅	详情	详情
(XXX)	26291	methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-4-cyanobutanoate		C₁₄H₁₆N₂O₄	详情	详情
(XXXI)	26292	(2S)-2-[[(benzyloxy)carbonyl]amino]-4-cyanobutyric acid		C₁₃H₁₄N₂O₄	详情	详情
(XXXII)	26293	(2S)-2-amino-4-cyanobutyric acid		C₅H₈N₂O₂	详情	详情
(XXXIII)	26294	(2S)-4-cyano-2-hydroxybutyric acid		C₅H₇NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The cyclization of N-(benzyloxycarbonyl)-L-glutamine (I) by means of CDI in THF gives the piperidinedione (II), which is deprotected by means of HBr in AcOH to yield 3(S)-aminopiperidine-2,6-dione (III).The condensation of (III) with 3-nitrophthalic anhydride (IV) in hot DMF/AcOH affords 3(S)-phthalimido-piperidine-2,6-dione (V), which is finally reduced with H2 over Pd/C in dioxane/methanol to provide the target thalidomide derivative.

参考文献中间体

合成目标

【1】 D'Amato, R.J.; Shah, J.H.; Hunsucker, K.A.; Pribluda, V.; Treston, A.; Rougas, J.; Conner, B.P.; Swartz, G.M. (Children's Medical Center Corp.); Synthesis of 3-amino-thalidomide and its enantiomers. WO 0264083 .

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)	26289	(2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid		C₁₃H₁₆N₂O₅	详情	详情
(II)	64520	benzyl (3S)-2,6-dioxopiperidinylcarbamate		C₁₃H₁₄N₂O₄	详情	详情
(III)	48171	(3S)-3-amino-2,6-piperidinedione		C₅H₈N₂O₂	详情	详情
(IV)	46407	4-nitro-2-benzofuran-1,3-dione；3-nitrophthalic anhydride	641-70-3	C₈H₃NO₅	详情	详情
(V)	34429	2-[(3S)-2,6-dioxopiperidinyl]-4-nitro-1H-isoindole-1,3(2H)-dione		C₁₃H₉N₃O₆	详情	详情

Extended Information