(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-5-yl)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】42808

【品名】(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-5-yl)propionic acid

【CA登记号】17791-52-5

【分子式】C₁₁H₁₇N₃O₄

【分子量】255.2738

【元素组成】C 51.76% H 6.71% N 16.46% O 25.07%

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：(V)

Acylation of the tertiary 20-hydroxy group of camptothecin (I) with N-Boc-valine-N-carboxyanhydride (II) afforded the corresponding ester (III). Subsequent acidic N-Boc group cleavage gave amino ester (IV). This was coupled with N-Boc-histidine (V) to furnish, after treatment with trifluoroacetic acid, the histidyl-valyl camptothecin ester (VI).

参考文献中间体

合成目标

【1】 Lerchen, H.-G.; et al.; Design and optimization of 20-O-linked camptothecin glyconjugates as anticancer agents. J Med Chem 2001, 44, 24, 4186.
【2】 Baumgarten, J.; Von dem Bruch, K.; Lerchen, H.-G.; Sperzel, M. (Bayer AG); 20(S) Camptothecin glycoconjugates. DE 19801037; DE 19813137; EP 0981542; JP 2001526661; WO 9851703 .

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)	25916	(4S)-4-hydroxy-4-methyl-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione		C₂₀H₁₆N₂O₄	详情	详情
(II)	35318	tert-butyl (4S)-4-isopropyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate	141468-55-5	C₁₁H₁₇NO₅	详情	详情
(III)	52487	4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-methylbutanoate		C₃₀H₃₃N₃O₇	详情	详情
(IV)	52488	4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 2-amino-3-methylbutanoate		C₂₅H₂₅N₃O₅	详情	详情
(V)	42808	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-5-yl)propionic acid	17791-52-5	C₁₁H₁₇N₃O₄	详情	详情
(VI)	52489	4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 2-{[2-amino-3-(1H-imidazol-5-yl)propanoyl]amino}-3-methylbutanoate		C₃₁H₃₂N₆O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Butylmagnesium bromide (II) was added to the Weinreb amide of Boc-L-leucine (I), yielding ketone (III), which was further reduced with NaBH4 to give alcohol (IV) as a diastereomeric mixture. The Boc protecting group of (IV) was removed employing trifluoroacetic acid in CH2Cl2, and the resulting amino alcohol (V) was coupled with N-Boc-L-histidine (VI) by means of BOP reagent to afford amide (VII). Deprotection of the Boc group of (VII) with trifluoroacetic acid then furnished the target C-terminal fragment (VIII).

参考文献中间体

合成目标

【1】 Cristau, M.; et al.; Synthesis and biological evaluation of bombesin constrained analogues. J Med Chem 2000, 43, 12, 2356.

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)	40395	tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-methylbutylcarbamate		C₁₃H₂₆N₂O₄	详情	详情
(II)	42802	bromo(butyl)magnesium	693-03-8	C₄H₉BrMg	详情	详情
(III)	42803	tert-butyl (1S)-1-isobutyl-2-oxohexylcarbamate		C₁₅H₂₉NO₃	详情	详情
(IV)	42804	tert-butyl (1S)-2-hydroxy-1-isobutylhexylcarbamate		C₁₅H₃₁NO₃	详情	详情
(V)	42805	(4S)-4-amino-2-methyl-5-nonanol		C₁₀H₂₃NO	详情	详情
(VI)	42808	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-5-yl)propionic acid	17791-52-5	C₁₁H₁₇N₃O₄	详情	详情
(VII)	42806	tert-butyl (1S)-2-[[(1S)-2-hydroxy-1-isobutylhexyl]amino]-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate		C₂₁H₃₈N₄O₄	详情	详情
(VIII)	42807	(2S)-2-amino-N-[(1S)-2-hydroxy-1-isobutylhexyl]-3-(1H-imidazol-5-yl)propanamide		C₁₆H₃₀N₄O₂	详情	详情

Extended Information