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【结 构 式】 
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【分子编号】34805 【品名】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 【CA登记号】 |
【 分 子 式 】C38H46N6O4S 【 分 子 量 】682.88728 【元素组成】C 66.84% H 6.79% N 12.31% O 9.37% S 4.7% |
合成路线1
该中间体在本合成路线中的序号：(XVI)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.
| 【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 |