N-Carbobenzyloxyglycine; 2-[[(benzyloxy)carbonyl]amino]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】17764

【品名】N-Carbobenzyloxyglycine; 2-[[(benzyloxy)carbonyl]amino]acetic acid

【CA登记号】1138-80-3

【分子式】C₁₀H₁₁NO₄

【分子量】209.20168

【元素组成】C 57.41% H 5.3% N 6.7% O 30.59%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

Benzyloxycarbonylglycine (I) was coupled with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide (DCC), and the resulting succinimidyl active ester (II) was condensed with dimiristylamine (III) to afford amide (IV). The benzyloxycarbonyl group was then removed by hydrogenolysis in the presence of palladium on carbon to yield amine (V). Coupling of this amine with Boc-protected L-arginine (VI) in the presence of diisopropylcarbodiimide (DIC) gave dipeptide (VII). Finally, partial deprotection of Boc groups with hydrochloric acid in dioxane provided the title compound.

参考文献中间体

合成目标

【1】 Lewis, J.G.; et al.; A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA. Proc Natl Acad Sci USA 1996, 93, 8, 3177.
【2】 Deprince, R.B.; Facchine, K.L.; Lewis, G.S.; Lewis, J.G.; Lin, K.-Y.; Matteucci, M.D.; Mook, R.A. Jr.; Wagner, R.W. (Gilead Sciences Inc.; Glaxo Wellcome plc); Cationic lipids for delivery of nucleic acids to cells. WO 9601841 .

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)	17764	N-Carbobenzyloxyglycine; 2-[[(benzyloxy)carbonyl]amino]acetic acid	1138-80-3	C₁₀H₁₁NO₄	详情	详情
(II)	17765	benzyl 2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethylcarbamate; Z-glycine N-succinimidyl ester	2899-60-7	C₁₄H₁₄N₂O₆	详情	详情
(III)	17766	DITETRADECYLAMINE; N-tetradecyl-1-tetradecanamine; N,N-ditetradecylamine	17361-44-3	C₂₈H₅₉N	详情	详情
(IV)	17767	benzyl 2-(ditetradecylamino)-2-oxoethylcarbamate		C₃₈H₆₈N₂O₃	详情	详情
(V)	17768	2-amino-N,N-ditetradecylacetamide		C₃₀H₆₂N₂O	详情	详情
(VI)	17769	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[(tert-butoxycarbonyl)[imino(methylamino)methyl]amino]pentanoic acid		C₁₇H₃₂N₄O₆	详情	详情
(VII)	17770	tert-butyl (4S)-4-[(tert-butoxycarbonyl)amino]-5-[[2-(ditetradecylamino)-2-oxoethyl]amino]-5-oxopentyl[[(tert-butoxycarbonyl)amino](imino)methyl]carbamate		C₅₁H₉₈N₆O₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Condensation of the secondary amine (I) with N5-Boc-N2-Z-ornithine (II) using EDC provided the acetal amide (III), and subsequent acid-catalyzed intramolecular cyclization of (III) in hot toluene gave rise to the pyrazinone (IV). Catalytic hydrogenation of the double bond with concomitant hydrogenolysis of the benzyloxycarbonyl group of (IV) provided the 1,3-substituted-2-oxopiperazine (V). This was condensed with Z-glycine (VI) to give amide (VII). Then, acid cleavage of the tert-butyl ester and N-Boc protecting groups of (VII) provided (VIII). The N-benzyloxycarbonyl group of (VIII) was subsequently removed by hydrogenolysis, yielding diamine (IX). Finally, acylation of (IX) with the imido ester of 4-guanidinobenzoic acid (X) furnished the title bis(4-guanidinobenzamide).

参考文献中间体

合成目标

【1】 Kitamura, S.; et al.; Potent dibasic GPIIb/IIIA antagonists with reduces prolongation of bleeding time: Synthesis and pharmacological evaluation of 2-oxopiperazine. J Med Chem 2001, 44, 15, 2438.
【2】 Fukushi, H.; Naka, T.; Terashita, Z.; Miyawaki, T. (Takeda Chemical Industries, Ltd.); Piperazinones useful as inhibitors of platelet aggregation. EP 0822931; JP 1997316059; US 5935963; US 6020334; WO 9633982 .

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)	50632	tert-butyl 2-[(2,2-dimethoxyethyl)amino]acetate		C₁₀H₂₁NO₄	详情	详情
(II)	50190	(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid		C₁₈H₂₆N₂O₆	详情	详情
(III)	50633	tert-butyl 2-[[(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoyl](2,2-dimethoxyethyl)amino]acetate		C₂₈H₄₅N₃O₉	详情	详情
(IV)	50634	benzyl (2S)-2-[3-[(tert-butoxycarbonyl)amino]propyl]-4-[2-(tert-butoxy)-2-oxoethyl]-3-oxo-3,4-dihydro-1(2H)-pyrazinecarboxylate		C₂₆H₃₇N₃O₇	详情	详情
(V)	50635	tert-butyl 2-((3S)-3-[3-[(tert-butoxycarbonyl)amino]propyl]-2-oxopiperazinyl)acetate		C₁₈H₃₃N₃O₅	详情	详情
(VI)	17764	N-Carbobenzyloxyglycine; 2-[[(benzyloxy)carbonyl]amino]acetic acid	1138-80-3	C₁₀H₁₁NO₄	详情	详情
(VII)	50639	tert-butyl 2-((3S)-4-(2-[[(benzyloxy)carbonyl]amino]acetyl)-3-[3-[(tert-butoxycarbonyl)amino]propyl]-2-oxopiperazinyl)acetate		C₂₈H₄₂N₄O₈	详情	详情
(VIII)	50636	2-[(3S)-3-(3-aminopropyl)-4-(2-[[(benzyloxy)carbonyl]amino]acetyl)-2-oxopiperazinyl]acetic acid		C₁₉H₂₆N₄O₆	详情	详情
(IX)	50637	2-[(3S)-4-(2-aminoacetyl)-3-(3-aminopropyl)-2-oxopiperazinyl]acetic acid		C₁₁H₂₀N₄O₄	详情	详情
(X)	50638	N-(4-[[(3,5-dioxo-4-azatricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)oxy]carbonyl]phenyl)guanidine		C₁₇H₁₆N₄O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XIX)

The pentaamino compound (XVIII) was coupled with N-(benzyloxycarbonyl)glycine (XIX) employing EDC and HOBt to afford penta amide (XX). The carbobenzoy protecting groups of (XX) were then removed by hydrogenation over PtO2 to give (XXI). Finally, installation of the guanidino groups in (XXI) was carried out by condensation with N,N'-di(carbobenzoxy)-S-methylisothiourea (XXII), followed by hydrogenolysis of the carbobenzoxy groups.

参考文献中间体

合成目标

【1】 Xuereb, H.; et al.; Design of an Oligosaccharide Scaffold that binds in the minor groove of DNA. J Am Chem Soc 2000, 122, 9, 1883-90.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVIII)	40234			C₈₂H₁₀₆N₁₀O₂₆	详情	详情
(XIX)	17764	N-Carbobenzyloxyglycine; 2-[[(benzyloxy)carbonyl]amino]acetic acid	1138-80-3	C₁₀H₁₁NO₄	详情	详情
(XX)	40235			C₄₂H₇₆N₁₀O₁₆	详情	详情
(XXI)	40236	ethyl (2E,4E)-2,4-hexadienoate	2396-84-1	C₈H₁₂O₂	详情	详情
(XXII)	32861	benzyl (E)-[[(benzyloxy)carbonyl]amino](methylsulfanyl)methylidenecarbamate		C₁₈H₁₈N₂O₄S	详情	详情

Extended Information