2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】52441

【品名】2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetic acid

【CA登记号】

【分子式】C₁₈H₁₇NO₄

【分子量】311.33732

【元素组成】C 69.44% H 5.5% N 4.5% O 20.56%

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：(XVII)

Coupling of resin (XVI) with N-Fmoc-sarcosine (XVII), followed by treatment with piperidine, provides (XVIII). This is treated with acetic acid and HBTU, producing the N-acetylated peptide resin (XIX). Cleavage of (XIX) from the resin in the presence of ethylamine leads to the side-chain protected peptide amide (XX).

参考文献中间体

合成目标

【1】 Haviv, F.; Kalvin, D.M.; Henkin, J.; Bradley, M.F.; Schneider, A.J. (Abbott Laboratories Inc.); Peptide antiangiogenic drugs. JP 2002516342; WO 9961476 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVI)	61401	(2S)-1-{(2S,5S,8S,11S,14R,17S)-20-amino-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-17-isopropyl-5,14-bis[(1S)-1-methylpropyl]-4,7,10,13,16,19-hexaoxo-8-propyl-3,6,9,12,15,18-hexaazaicos-1-anoyl}-2-pyrrolidinecarboxylic acid	C₅₇H₉₉N₁₁O₁₃S	详情	详情
(XVII)	52441	2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetic acid	C₁₈H₁₇NO₄	详情	详情
(XVIII)	61402	(2S)-1-{(2S,5S,8S,11S,14R,17S)-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-17-isopropyl-5,14-bis[(1S)-1-methylpropyl]-4,7,10,13,16,19,22-heptaoxo-8-propyl-3,6,9,12,15,18,21,24-octaazapentacos-1-anoyl}-2-pyrrolidinecarboxylic acid	C₆₀H₁₀₄N₁₂O₁₄S	详情	详情
(XIX)	61403	(2S)-1-{(2S,5S,8S,11S,14R,17S)-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-17-isopropyl-24-methyl-5,14-bis[(1S)-1-methylpropyl]-4,7,10,13,16,19,22,25-octaoxo-8-propyl-3,6,9,12,15,18,21,24-octaazahexacos-1-anoyl}-2-pyrrolidinecarboxylic acid	C₆₂H₁₀₆N₁₂O₁₅S	详情	详情
(XX)	61404	(2S)-1-{(2S,5S,8S,11S,14R,17S)-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-17-isopropyl-24-methyl-5,14-bis[(1S)-1-methylpropyl]-4,7,10,13,16,19,22,25-oc	C₆₄H₁₁₁N₁₃O₁₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

The deprotection of Wang-RESIN-coupled N-Fmoc-D-aspartic acid alpha-methyl ester (XII) with piperidine in DMF gives the free RESIN-coupled aspartic acid monoester (XIII), which is condensed with N-Fmoc-sarcosine (XIV) by means of PyBOP in DMF to yield the dipeptide (XV). Deprotection with piperidine affords (XVI), and coupling with PyBOP was repeated with the L-glutamate (XVII) to afford tripeptide (XVIII); with deprotected (XIX) and the intermediate amino acid (XI) to provide tetrapeptide (XX); and with deprotected (XXI) and -Fmoc-L-phenylalanine (XXII) to furnish finally the protected RESIN-bounded pentapeptide (XXIII).

参考文献中间体

合成目标

【1】 O'Donnell, M.E.; et al.; Serine-threonine protein phosphatase inhibitors derived from nodularin: Role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint. J Chem Soc - Perkins Trans I 2001, 14, 1696.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	52438	3-({[(9H-fluoren-9-ylmethyl)oxy]carbonyl}amino)-2-methyl-5-phenyl-4-pentenoic acid		C₂₇H₂₅NO₄	详情	详情
(XII)	52439	3-({[(9H-fluoren-9-ylmethyl)oxy]carbonyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₂₀H₁₉NO₆	详情	详情
(XIII)	52440	3-amino-4-(methyloxy)-4-oxobutanoic acid		C₅H₉NO₄	详情	详情
(XIV)	52441	2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetic acid		C₁₈H₁₇NO₄	详情	详情
(XV)	52442	3-({2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₂₃H₂₄N₂O₇	详情	详情
(XVI)	52443	3-{[2-(methylamino)acetyl]amino}-4-(methyloxy)-4-oxobutanoic acid		C₈H₁₄N₂O₅	详情	详情
(XVII)	52444	4-({[(9H-fluoren-9-ylmethyl)oxy]carbonyl}amino)-5-(methyloxy)-5-oxopentanoic acid		C₂₁H₂₁NO₆	详情	详情
(XVIII)	52445	1-(9H-fluoren-9-yl)-9-methyl-5,13-bis[(methyloxy)carbonyl]-3,8,11-trioxo-2-oxa-4,9,12-triazapentadecan-15-oic acid		C₂₉H₃₃N₃O₁₀	详情	详情
(XIX)	52446	3-({2-[[4-amino-5-(methyloxy)-5-oxopentanoyl](methyl)amino]acetyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₁₄H₂₃N₃O₈	详情	详情
(XX)	52447	1-(9H-fluoren-9-yl)-6,13-dimethyl-9,17-bis[(methyloxy)carbonyl]-3,7,12,15-tetraoxo-5-(2-phenylethenyl)-2-oxa-4,8,13,16-tetraazanonadecan-19-oic acid		C₄₁H₄₆N₄O₁₁	详情	详情
(XXI)	52448	3-({2-[[4-[(3-amino-2-methyl-5-phenyl-4-pentenoyl)amino]-5-(methyloxy)-5-oxopentanoyl](methyl)amino]acetyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₂₆H₃₆N₄O₉	详情	详情
(XXII)	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
(XXIII)	52449	1-(9H-fluoren-9-yl)-9,16-dimethyl-12,20-bis[(methyloxy)carbonyl]-3,6,10,15,18-pentaoxo-8-(2-phenylethenyl)-5-(phenylmethyl)-2-oxa-4,7,11,16,19-pentaazadocosan-22-oic acid		C₅₀H₅₅N₅O₁₂	详情	详情

Extended Information