(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】50190

【品名】(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid

【CA登记号】

【分子式】C₁₈H₂₆N₂O₆

【分子量】366.41432

【元素组成】C 59% H 7.15% N 7.65% O 26.2%

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：(II)

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2

该中间体在本合成路线中的序号：(VII)

Wittig reaction between aldehyde (I) and methyl(triphenylphosphoranylidene triphenyl)-acetate (II) in refluxing toluene provides E-olefin (III), which is then subjected to reaction with lithium derivative (IV) in THF to afford adduct (V). Benzyl groups of (V) are removed by hydrogenation over Pd(OH)2 in HOAc:MeOH:EtOAc to furnish amine (VI), which is then coupled to Z-Orn(Boc)-OH using 1-ethyl-3-dimethylaminopropylcarbodiimide (WSCD.HCl) and HOBt in CH2Cl2 to give beta-amino acid derivative (VIII). Saponification of the methyl ester group in (VIII) by means of LiOH, followed by condensation with HOBt by means of WSCD.HCl, yields activated ester (IX).

参考文献中间体

合成目标

【1】 Hashimoto, S.; Hashimoto, M.; Tanaka, A.; Fujie, A.; Shigematsu, N.; Barrett, D.; An expedient synthesis of the amide analog of the potent antifungal lipopeptidolactone FR901469. Tetrahedron Lett 2001, 42, 4, 703.

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)	50186	Myristaldehyde; Myristyl aldehyde; Tetradecanal; Myristic aldehyde trimer; Tetradecyl aldehyde	124-25-4	C₁₄H₂₈O	详情	详情
(II)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(III)	50187	methyl (E)-2-hexadecenoate		C₁₇H₃₂O₂	详情	详情
(IV)	30864	N-Benzyl-N-(1(R)-phenylethyl)amide lithium salt		C₁₅H₁₆LiN	详情	详情
(V)	50188	methyl (3R)-3-[benzyl[(1R)-1-phenylethyl]amino]hexadecanoate		C₃₂H₄₉NO₂	详情	详情
(VI)	50189	methyl (3R)-3-aminohexadecanoate		C₁₇H₃₅NO₂	详情	详情
(VII)	50190	(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid		C₁₈H₂₆N₂O₆	详情	详情
(VIII)	50191	methyl (3R)-3-([(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoyl]amino)hexadecanoate		C₃₅H₅₉N₃O₇	详情	详情
(IX)	50192	tert-butyl (4S)-5-([(1R)-1-[2-(1H-1,2,3-benzotriazol-1-yloxy)-2-oxoethyl]tetradecyl]amino)-4-[[(benzyloxy)carbonyl]amino]-5-oxopentylcarbamate		C₄₀H₆₀N₆O₇	详情	详情

Extended Information