2-[4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】27107

【品名】2-[4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid

【CA登记号】

【分子式】C₁₆H₁₆N₂O₃

【分子量】284.31472

【元素组成】C 67.59% H 5.67% N 9.85% O 16.88%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIII)

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

合成路线2

该中间体在本合成路线中的序号：(XI)

Coupling of p-aminophenylacetic acid (IX) with o-tolyl isocyanate (X) produces urea (XI). This is subsequently condensed with the intermediate tripeptide (VIII) in the presence of HATU to yield amide (XII). Hydrogenolysis of the N-benzyloxycarbonyl group of (XII) then gives amine (XIII). Finally, acylation of amine (XIII) with 3,5-dichlorobenzensulfonyl chloride (XIV), followed by alkaline hydrolysis of the methyl ester group furnishes the title compound.

参考文献中间体

合成目标

【1】 Lee, W.-C.; Scott, D.; Cornebise, M.; Petter, R. (Biogen Idec Inc.); Cell adhesion inhibitors. EP 1265606; JP 2003506491; US 6630503; WO 0112186 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	64990	phenylmethyl 2-[({3-{[4-methyl-2-(methylamino)pentanoyl]amino}-1-[(methyloxy)carbonyl]propyl}amino)carbonyl]-1-pyrrolidinecarboxylate		C₂₅H₃₈N₄O₆	详情	详情
(IX)	21229	2-(4-Aminophenyl)acetic acid	5345-54-0	C₈H₉NO₂	详情	详情
(X)	27106	1-isocyanato-2-methylbenzene	614-68-6	C₈H₇NO	详情	详情
(XI)	27107	2-[4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid		C₁₆H₁₆N₂O₃	详情	详情
(XII)	64991	phenylmethyl 2-[({3-{[4-methyl-2-(methyl{2-[4-({[(2-methylphenyl)amino]carbonyl}amino)phenyl]acetyl}amino)pentanoyl]amino}-1-[(methyloxy)carbonyl]propyl}amino)carbonyl]-1-pyrrolidinecarboxylate		C₄₁H₅₂N₆O₈	详情	详情
(XIII)	64992	methyl 4-{[4-methyl-2-(methyl{2-[4-({[(2-methylphenyl)amino]carbonyl}amino)phenyl]acetyl}amino)pentanoyl]amino}-2-[(2-pyrrolidinylcarbonyl)amino]butanoate		C₃₃H₄₆N₆O₆	详情	详情
(XIV)	59023	3,5-dichlorobenzenesulfonyl chloride		C₆H₃Cl₃O₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Reduction of methyl 3-(4-nitrophenyl)butyrate (I) with H2 in the presence of Pd/C produces aniline (II). This is then coupled with [N'-(2-methylphenyl)ureido]phenylacetic acid (III) by means of HATU, yielding amide (IV). Finally, ester group hydrolysis in (IV) with LiOH gives rise to the title carboxylic acid.

参考文献中间体

合成目标

【1】 Singh, J.; van Vlijmen, H.; Liao, Y.; Lee, W.-C.; Cornebise, M.; Harris, M.; Shu, I.-h.; Gill, A.; Cuervo, J.H.; Abraham, W.M.; Adams, S.P.; Identification of potent and novel alpha4beta1 antagonists using in silico screening. J Med Chem 2002, 45, 14, 2988.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	65109	methyl 3-(4-nitrophenyl)butanoate	C₁₁H₁₃NO₄	详情	详情
(II)	65110	methyl 3-(4-aminophenyl)butanoate	C₁₁H₁₅NO₂	详情	详情
(III)	27107	2-[4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid	C₁₆H₁₆N₂O₃	详情	详情
(IV)	65111	methyl 3-{4-[(2-{4-[(2-toluidinocarbonyl)amino]phenyl}acetyl)amino]phenyl}butanoate	C₂₇H₂₉N₃O₄	详情	详情

Extended Information