(2R)-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 -Drug Synthesis Database

【结构式】

【分子编号】49886

【品名】(2R)-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

【CA登记号】

【分子式】C₃₅H₄₄N₄O₇S

【分子量】664.82312

【元素组成】C 63.23% H 6.67% N 8.43% O 16.85% S 4.82%

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)

The title compound is prepared by solid-phase peptide synthesis using an automatic peptide synthesizer. To the L-proline attached to the resin support (I) is coupled Fmoc-L-Arg(Pmc)-OH (II) under activation with HBTU/HOBt to produce the protected dipeptide resin (III). The N-Fmoc group of (III) is then removed by means of piperidine in DMF, yielding the deprotected amine (IV). Subsequent coupling with N-Fmoc-L-isoleucine (V), followed by deprotection with piperidine in DMF, leads to the tripeptide resin (VI). Further coupling/deprotection cycles with N-Fmoc-L-norvaline (VII) and N-Fmoc-O-t-butyl-L-threonine (IX) produce resins (VIII) and (X) respectively.

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	CAS号	分子式	供应商	用于合成
(I)	16731	L-proline	147-85-3	C₅H₉NO₂	详情	详情
(II)	49886	(2R)-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
(III)	61391	(2S)-1-{(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]pentanoyl}-2-pyrrolidinecarboxylic acid		C₄₀H₅₁N₅O₈S	详情	详情
(IV)	61392	(2S)-1-{(2S)-2-amino-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid		C₂₅H₄₁N₅O₆S	详情	详情
(V)	61393	(2S,3S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-methylpentanoic acid		C₂₁H₂₃NO₄	详情	详情
(VI)	61394	(2S)-1-{(2S)-2-{[(2S,3S)-2-amino-3-methylpentanoyl]amino}-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid		C₃₁H₅₂N₆O₇S	详情	详情
(VII)	61395	(2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}pentanoic acid		C₂₀H₂₁NO₄	详情	详情
(VIII)	61396	(2S)-1-{(2S)-2-[((2S,3S)-2-{[(2S)-2-aminopentanoyl]amino}-3-methylpentanoyl)amino]-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid		C₃₆H₆₁N₇O₈S	详情	详情
(IX)	61397	tert-butyl (2S,3R)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-hydroxybutanoate		C₂₃H₂₇NO₅	详情	详情
(X)	61398	(2S)-1-{(2S,5S,8S,11S,12R)-11-amino-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-12,14,14-trimethyl-5-[(1S)-1-methylpropyl]-4,7,10-trioxo-8-propyl-13-oxa-3,6,9-triazapentadec-1-anoyl}-2-pyrrolidinecarboxylic acid		C₄₄H₇₆N₈O₁₀S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Coupling of Fmoc-D-arginine(PMC) (I) with phenylalaninol methyl ether (II) in the presence of EDC and HOBt provided amide (III). Cleavage of the Fmoc group by using piperidine in DMF afforded amine (IV), which was subsequently coupled with dinaphthylpropionic acid (V), yielding diamide (VI). The pentamethylchromansulfonyl protecting group (PMC) was finally removed by treatment with trifluoroacetic acid in the presence of ethanedithiol and anisole.

参考文献中间体

合成目标

【1】 Daniels, A.J.; Heyer, D.; Leban, J.J. (Glaxo Wellcome plc); Modified peptides. WO 9622305 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	49886	(2R)-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
(II)	49881	(2S)-1-methoxy-3-phenyl-2-propanamine; (1S)-1-benzyl-2-methoxyethylamine	C₁₀H₁₅NO	详情	详情
(III)	49882	9H-fluoren-9-ylmethyl (1R)-1-([[(1S)-1-benzyl-2-methoxyethyl]amino]carbonyl)-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butylcarbamate	C₄₅H₅₇N₅O₇S	详情	详情
(IV)	49883	(2R)-2-amino-N-[(1S)-1-benzyl-2-methoxyethyl]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanamide	C₃₀H₄₇N₅O₅S	详情	详情
(V)	49884	3,3-di(1-naphthyl)propionic acid	C₂₃H₁₈O₂	详情	详情
(VI)	49885	(2R)-N-[(1S)-1-benzyl-2-methoxyethyl]-2-[[3,3-di(1-naphthyl)propanoyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanamide	C₅₃H₆₃N₅O₆S	详情	详情

Extended Information