(2S)-3-cyclohexyl-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid -Drug Synthesis Database

【结构式】

【分子编号】30827

【品名】(2S)-3-cyclohexyl-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid

【CA登记号】

【分子式】C₂₄H₂₇NO₄

【分子量】393.48272

【元素组成】C 73.26% H 6.92% N 3.56% O 16.26%

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：(VI)

The compound was prepared via solid-phase synthesis using Rink-amide resin (I). After initial Fmoc-deprotection of (I) with piperidine in DMF, Fmoc-L-phenylalanine (II) was coupled to the resin by means of N,N'-diisopropyl carbodiimide (DIC) and hydroxybenzotriazole (HOBt) in DMF, yielding the phenylalanine-linked resin (III). Subsequent Fmoc-deprotection and coupling cycles with protected arginine (IV) and cyclohexylalanine (VI) produced the peptide resins (V) and (VII), respectively. Further deprotection of (VII) with piperidine, followed by coupling with 5-bromonicotinic acid (VIII) gave the corresponding amide (IX). Cleavage of the final peptide amide from the resin (IX) was then accomplished by treatment trifluoroacetic acid and anisole.

参考文献中间体

合成目标

【1】 Addo, M.F.; Hawkins, M.J.; Maryanoff, B.E.; Oksenberg, D.; McComsey, D.F.; Andrade-Gordon, P.; Heterocycle-peptide hybrid compounds. Aminotriazole-containing agonists of the thrombin receptor (PAR-1). Bioorg Med Chem Lett 1999, 9, 10, 1423.
【2】 Hawkins, M.J.; Maryanoff, B.E.; McComsey, D.F. (Ortho-McNeil Pharmaceutical, Inc.); Substd. heterocyclic acyl-tripeptides useful as thrombin receptor modulators. WO 0035942 .

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)	28722	9H-fluoren-9-ylmethyl carbamate	84418-43-9	C₁₅H₁₃NO₂	详情	详情
(II)	19030	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid; N-((9H-fluoren-9-ylmethoxy)carbonyl)-phenylalanine	35661-40-6	C₂₄H₂₁NO₄	详情	详情
(III)	19031	9H-fluoren-9-ylmethyl (1S)-2-amino-1-benzyl-2-oxoethylcarbamate		C₂₄H₂₂N₂O₃	详情	详情
(IV)	30825	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid		C₃₅H₄₄N₄O₇S	详情	详情
(V)	30826	9H-fluoren-9-ylmethyl (1S)-1-([[(1S)-2-amino-1-benzyl-2-oxoethyl]amino]carbonyl)-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butylcarbamate		C₄₄H₅₄N₆O₇S	详情	详情
(VI)	30827	(2S)-3-cyclohexyl-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid		C₂₄H₂₇NO₄	详情	详情
(VII)	30828	9H-fluoren-9-ylmethyl (1S)-2-([(1S)-1-([[(1S)-2-amino-1-benzyl-2-oxoethyl]amino]carbonyl)-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)-1-(cyclohexylmethyl)-2-oxoethylcarbamate		C₅₃H₆₉N₇O₈S	详情	详情
(VIII)	17913	5-Bromonicotinic acid	20826-04-4	C₆H₄BrNO₂	详情	详情
(IX)	30829	N-[(1S)-2-([(1S)-1-([[(1S)-2-amino-1-benzyl-2-oxoethyl]amino]carbonyl)-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)-1-(cyclohexylmethyl)-2-oxoethyl]-5-bromonicotinamide		C₄₄H₆₁BrN₈O₇S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Coupling of N-alpha-Fmoc-N-epsilon-Boc-lysine (I) to 7-amino-4-methylcoumarin (II) by means of DCC produces the lysine amide (III). After acidic cleavage of the N-Boc protecting group of (III), the resultant primary amine (IV) is attached to chlorotrityl resin to produce (V). The Fmoc group of (V) is then removed with piperidine in DMF, yielding the lysinamide-bound resin (VI). Further coupling with N-Fmoc-cyclohexylalanine (VII) employing TBTU/HOAt furnishes the dipeptide amide resin (VIII). The title compound is finally cleaved from the solid support by means of trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Saar, K.; Mazarati, A.M.; Mahlapuu, R.; Hallnemo, G.; Soomets, U.; Kilk, K.; Hellberg, S.; Pooga, M.; Tolf, B.R.; Shi, T.S.; Hökfelt, T.; Wasterlain, C.; Bartfai, T.; Langel, U.; Anticonvulsant activity of a nonpeptide galanin receptor agonist. Proc Natl Acad Sci USA 2002, 99, 10, 7136.

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)	18854	(2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid		C₂₆H₃₂N₂O₆	详情	详情
(II)	64549	7-amino-4-methyl-2H-chromen-2-one		C₁₀H₉NO₂	详情	详情
(III)	64550	9H-fluoren-9-ylmethyl 5-[(tert-butoxycarbonyl)amino]-1-{[(4-methyl-2-oxo-2H-chromen-7-yl)amino]carbonyl}pentylcarbamate		C₃₆H₃₉N₃O₇	详情	详情
(IV)	64551	9H-fluoren-9-ylmethyl 5-amino-1-{[(4-methyl-2-oxo-2H-chromen-7-yl)amino]carbonyl}pentylcarbamate		C₃₁H₃₁N₃O₅	详情	详情
(VI)	64552	2,6-diamino-N-(4-methyl-2-oxo-2H-chromen-7-yl)hexanamide		C₁₆H₂₁N₃O₃	详情	详情
(VII)	30827	(2S)-3-cyclohexyl-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid		C₂₄H₂₇NO₄	详情	详情
(VIII)	64553	Galnon; Fmoc-beta-cyclohexyl-Ala-Lys-AMC	475115-35-6	C₄₀H₄₆N₄O₆	详情	详情

Extended Information