|
【结 构 式】 
|
【分子编号】32574 【品名】methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-nitrophenyl)propanoate 【CA登记号】 |
【 分 子 式 】C15H20N2O6 【 分 子 量 】324.33368 【元素组成】C 55.55% H 6.22% N 8.64% O 29.6% |
合成路线1
该中间体在本合成路线中的序号：(VII)Fischer esterification of L-4-nitrophenylalanine (V) afforded nitrophenylalanine methyl ester (VI), which was then protected as the tert-butyl carbamate (VII) using (Boc)2O. Reduction of the nitro group of (VII) by catalytic hydrogenation gave aniline (VIII). Subsequent coupling of (VIII) with 2,6-dichlorobenzoyl chloride (IX) generated amide (X). Deprotection of the Boc group of (X) using HCl in dioxan provided aminoester (XI), which was coupled with camphoric acid derivative (IV) in the presence of benzotriazolyloxy-tris(dimethylamino)phosphonium hexafluoro-phosphate (BOP) to yield amide (XII). Deprotection of the tert-butyl ester group of (XII) by means of trifluoroacetic acid gave acid (XIII). Finally, the methyl ester group of (XIII) was hydrolyzed with LiOH to furnish the title compound.
| 【1】 Rishton, G.; Chrusciel, R.A.; Yamagishi, M.; Polinsky, A.; Thomas, E.W.; Lobl, T.J.; Tanis, S.P.; Teegarden, B.; Fisher, J.F. (Pharmacia Corp.; Tanabe Seiyaku Co., Ltd.); Inhibitors of alpha4beta1 mediated cell adhesion. EP 0991619; WO 9858902 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 32572 | (1S,3R)-3-(tert-butoxycarbonyl)-2,2,3-trimethylcyclopentanecarboxylic acid | C14H24O4 | 详情 | 详情 | |
| (V) | 15341 | (2S)-2-amino-3-(4-nitrophenyl)propionic acid; 4-nitro-L-phenylalanine | 949-99-5 | C9H10N2O4 | 详情 | 详情 |
| (VI) | 15342 | methyl (2S)-2-amino-3-(4-nitrophenyl)propanoate | C10H12N2O4 | 详情 | 详情 | |
| (VII) | 32574 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-nitrophenyl)propanoate | C15H20N2O6 | 详情 | 详情 | |
| (VIII) | 32575 | methyl (2S)-3-(4-aminophenyl)-2-[(tert-butoxycarbonyl)amino]propanoate | C15H22N2O4 | 详情 | 详情 | |
| (IX) | 25087 | 2,6-dichlorobenzoyl chloride | 4659-45-4 | C7H3Cl3O | 详情 | 详情 |
| (X) | 32576 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate | C22H24Cl2N2O5 | 详情 | 详情 | |
| (XI) | 32578 | methyl (2S)-2-amino-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate | C17H16Cl2N2O3 | 详情 | 详情 | |
| (XII) | 32573 | tert-butyl (1R,3S)-3-[[((1S)-1-[4-[(2,6-dichlorobenzoyl)amino]benzyl]-2-methoxy-2-oxoethyl)amino]carbonyl]-1,2,2-trimethylcyclopentanecarboxylate | C31H38Cl2N2O6 | 详情 | 详情 | |
| (XIII) | 32577 | (1R,3S)-3-[[((1S)-1-[4-[(2,6-dichlorobenzoyl)amino]benzyl]-2-methoxy-2-oxoethyl)amino]carbonyl]-1,2,2-trimethylcyclopentanecarboxylic acid | C27H30Cl2N2O6 | 详情 | 详情 |