2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】34743

【品名】2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetic acid

【CA登记号】

【分子式】C₁₃H₁₁N₃O₂

【分子量】241.24936

【元素组成】C 64.72% H 4.6% N 17.42% O 13.26%

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：(XV)

Protection of 4-imidazoleacetic acid methyl ester (X) with triphenylmethyl bromide provided the N1-trityl derivative (XI). Subsequent alkylation of (XI) with 4-cyanobenzyl bromide (XII) resulted in the formation of the imidazolium salt (XIII). Deprotection of the trityl group of (XIII) was achieved upon refluxingin MeOH to give (XIV). Hydrolysis of the methyl ester group of (XIV) under either acidic or basic conditions yielded imidazoleacetic acid (XV), which was subsequently coupled with the intermediate amine (IX) using EDC and 3-hydroxy-1,2,3-benzotriazin-4-one (HOOBT) to provide amide (XVI). Finally, saponification of the methyl ester group of (XVI) furnished the title compound.

参考文献中间体

合成目标

【1】 Gomez, R.P.; Schaber, M.D.; Anthony, N.J.; et al.; Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase. J Med Chem 1999, 42, 17, 3356.
【2】 Anthony, N.J.; Desolms, S.J.; Gomez, R.P.; Graham, S.L.; Hutchinson, J.H.; Stokker, G.E. (Merck & Co., Inc.); Thio-free inhibitors of farnesyl-protein transferase. JP 1998508005; US 5652257; WO 9610034 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	34738	methyl (2S)-2-([2-[[(2S,3S)-2-amino-3-methylpentyl](1-naphthylmethyl)amino]acetyl]amino)-4-(methylsulfanyl)butanoate		C₂₅H₃₇N₃O₃S	详情	详情
(X)	34739	methyl 2-(1H-imidazol-4-yl)acetate		C₆H₈N₂O₂	详情	详情
(XI)	34740	methyl 2-(1-trityl-1H-imidazol-4-yl)acetate		C₂₅H₂₂N₂O₂	详情	详情
(XII)	14200	4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile	17201-43-3	C₈H₆BrN	详情	详情
(XIII)	34741	3-(4-cyanobenzyl)-4-(2-methoxy-2-oxoethyl)-1-trityl-1H-imidazol-3-ium bromide		C₃₃H₂₈BrN₃O₂	详情	详情
(XIV)	34742	methyl 2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetate		C₁₄H₁₃N₃O₂	详情	详情
(XV)	34743	2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetic acid		C₁₃H₁₁N₃O₂	详情	详情
(XVI)	34805	methyl (2S)-2-([2-[[(2S,3S)-2-([2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetyl]amino)-3-methylpentyl](1-naphthylmethyl)amino]acetyl]amino)-4-(methylsulfanyl)butanoate		C₃₈H₄₆N₆O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

Protection of 4-imidazoleacetic acid methyl ester (X) with triphenylmethyl bromide provided the N1-trityl derivative (XI). Subsequent alkylation with 4-cyanobenzyl bromide (XII) resulted in the formation of the imidazolium salt (XIII). Deprotection of the trityl group of (XIII) was achieved upon refluxingin MeOH to give (XIV). Hydrolysis of the methyl ester group of (XIV) under either acidic or basic conditions yielded imidazoleacetic acid (XV). This was finally coupled with the intermediate amine (IX) using EDC and 3-hydroxy-1,2,3-benzotriazin-4-one (HOOBT) to provide the title compound.

参考文献中间体

合成目标

【1】 Gomez, R.P.; Schaber, M.D.; Anthony, N.J.; et al.; Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase. J Med Chem 1999, 42, 17, 3356.
【2】 Anthony, N.J.; Desolms, S.J.; Gomez, R.P.; Graham, S.L.; Hutchinson, J.H.; Stokker, G.E. (Merck & Co., Inc.); Thio-free inhibitors of farnesyl-protein transferase. JP 1998508005; US 5652257; WO 9610034 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	34738	methyl (2S)-2-([2-[[(2S,3S)-2-amino-3-methylpentyl](1-naphthylmethyl)amino]acetyl]amino)-4-(methylsulfanyl)butanoate		C₂₅H₃₇N₃O₃S	详情	详情
(X)	34739	methyl 2-(1H-imidazol-4-yl)acetate		C₆H₈N₂O₂	详情	详情
(XI)	34740	methyl 2-(1-trityl-1H-imidazol-4-yl)acetate		C₂₅H₂₂N₂O₂	详情	详情
(XII)	14200	4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile	17201-43-3	C₈H₆BrN	详情	详情
(XIII)	34741	3-(4-cyanobenzyl)-4-(2-methoxy-2-oxoethyl)-1-trityl-1H-imidazol-3-ium bromide		C₃₃H₂₈BrN₃O₂	详情	详情
(XIV)	34742	methyl 2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetate		C₁₄H₁₃N₃O₂	详情	详情
(XV)	34743	2-[1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetic acid		C₁₃H₁₁N₃O₂	详情	详情

Extended Information