benzyl (2S)-1-((2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-4-(benzyloxy)-4-oxobutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】27105

【品名】benzyl (2S)-1-((2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-4-(benzyloxy)-4-oxobutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylate

【CA登记号】

【分子式】C₃₄H₄₆N₄O₇

【分子量】622.762

【元素组成】C 65.57% H 7.45% N 9% O 17.98%

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：(X)

N-Boc-L-Valine N-hydroxysuccinimidyl ester (I) was coupled to L-proline benzyl ester (II), and the resulting Boc dipeptide (III) was subsequently deprotected with trifluoroacetic acid in CH2Cl2 to afford (IV). This was condensed with N-Boc-L-aspartic acid gamma-benzyl 1-N-hydroxysuccinimidyl diester (V) to give (VI). After Boc deprotection of (VI) with trifluoroacetic acid, tripeptide (VII) was coupled with N-Boc-L-leucine N-hydroxysuccinimidyl ester (VIII) to yield tetrapeptide (IX). Further Boc deprotection of (IX) with trifluoroacetic acid furnished peptide intermediate (X).

参考文献中间体

合成目标

【1】 Ateeq, H.S.; Lin, K.-C.; Hsiung, S.H.; et al.; Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses. J Med Chem 1999, 42, 5, 920.
【2】 Lin, K.-C.; Adams, S.P.; Castro, A.C.; Zimmerman, C.N.; Cuervo, J.H.; Lee, W.-C.; Hammond, C.E.; Carter, M.B.; Almquist, R.G.; Ensinger, C.L. (Biogen, Inc.); Cell adhesion inhibitor. EP 0842196; JP 1999511124; WO 9703094 .

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)	27097	tert-butyl (1S)-1-[[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)oxy]carbonyl]-2-methylpropylcarbamate		C₁₄H₂₀N₂O₆	详情	详情
(II)	20930	benzyl (2S)-2-pyrrolidinecarboxylate	16652-71-4	C₁₂H₁₅NO₂	详情	详情
(III)	27098	benzyl (2S)-1-[(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]-2-pyrrolidinecarboxylate		C₂₂H₃₂N₂O₅	详情	详情
(IV)	27099	benzyl (2S)-1-[(2S)-2-amino-3-methylbutanoyl]-2-pyrrolidinecarboxylate		C₁₇H₂₄N₂O₃	详情	详情
(V)	27100	benzyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)oxy]-4-oxobutanoate		C₂₀H₂₂N₂O₈	详情	详情
(VI)	27101	benzyl (2S)-1-[(2S)-2-([(2S)-4-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutanoyl]amino)-3-methylbutanoyl]-2-pyrrolidinecarboxylate		C₃₃H₄₃N₃O₈	详情	详情
(VII)	27102	benzyl (2S)-1-((2S)-2-[[(2S)-2-amino-4-(benzyloxy)-4-oxobutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylate		C₂₈H₃₅N₃O₆	详情	详情
(VIII)	27103	tert-butyl (1S)-1-[[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)oxy]carbonyl]-3-methylbutylcarbamate		C₁₅H₂₂N₂O₆	详情	详情
(IX)	27104	benzyl (2S)-1-[(2S,5S,8S)-5-[2-(benzyloxy)-2-oxoethyl]-8-isobutyl-2-isopropyl-12,12-dimethyl-4,7,10-trioxo-11-oxa-3,6,9-triazatridec-1-anoyl]-2-pyrrolidinecarboxylate		C₃₉H₅₄N₄O₉	详情	详情
(X)	27105	benzyl (2S)-1-((2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-4-(benzyloxy)-4-oxobutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylate		C₃₄H₄₆N₄O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Condensation of o-tolyl isocyanate (XI) with 4-aminophenylacetic acid (XII) produced urea (XIII). This was coupled to tetrapeptide (X) using EDC and HOBt to give the corresponding amide (XIV). Finally, the benzyl ester groups of (XIV) were deprotected by hydrogenolysis over Pd/C.

参考文献中间体

合成目标

【1】 Ateeq, H.S.; Lin, K.-C.; Hsiung, S.H.; et al.; Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses. J Med Chem 1999, 42, 5, 920.
【2】 Lin, K.-C.; Adams, S.P.; Castro, A.C.; Zimmerman, C.N.; Cuervo, J.H.; Lee, W.-C.; Hammond, C.E.; Carter, M.B.; Almquist, R.G.; Ensinger, C.L. (Biogen, Inc.); Cell adhesion inhibitor. EP 0842196; JP 1999511124; WO 9703094 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	27105	benzyl (2S)-1-((2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-4-(benzyloxy)-4-oxobutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylate		C₃₄H₄₆N₄O₇	详情	详情
(XI)	27106	1-isocyanato-2-methylbenzene	614-68-6	C₈H₇NO	详情	详情
(XII)	21229	2-(4-Aminophenyl)acetic acid	5345-54-0	C₈H₉NO₂	详情	详情
(XIII)	27107	2-[4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid		C₁₆H₁₆N₂O₃	详情	详情
(XIV)	27108	benzyl (2S)-1-((2S)-2-[[(2S)-4-(benzyloxy)-2-([(2S)-4-methyl-2-[(2-[4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]pentanoyl]amino)-4-oxobutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylate		C₅₀H₆₀N₆O₉	详情	详情

Extended Information