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【结 构 式】 
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【分子编号】64990 【品名】phenylmethyl 2-[({3-{[4-methyl-2-(methylamino)pentanoyl]amino}-1-[(methyloxy)carbonyl]propyl}amino)carbonyl]-1-pyrrolidinecarboxylate 【CA登记号】 |
【 分 子 式 】C25H38N4O6 【 分 子 量 】490.60008 【元素组成】C 61.21% H 7.81% N 11.42% O 19.57% |
合成路线1
该中间体在本合成路线中的序号：(VIII)2-N-(Benzyloxycarbonyl)-L-2,4-diaminobutyric acid (I) is esterified by means of SOCl2 in MeOH to afford the corresponding methyl ester (II). Subsequent coupling of (II) with N-Boc-N-methyl-L-leucine (III) leads to dipeptide (IV). The N-benzyloxycarbonyl group of (IV) is removed by catalytic hydrogenation over Pd/C to furnish amine (V), which is further acylated with N-benzyloxycarbonyl-L-proline succinimidyl ester (VI) yielding tripeptide (VII). Then, acidic cleavage of the N-Boc protecting group (VII) produces (VIII).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 64984 | 4-amino-2-({[(phenylmethyl)oxy]carbonyl}amino)butanoic acid | C12H16N2O4 | 详情 | 详情 | |
| (II) | 64985 | methyl 4-amino-2-({[(phenylmethyl)oxy]carbonyl}amino)butanoate | C13H18N2O4 | 详情 | 详情 | |
| (III) | 26295 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoic acid | 609-23-4 | C12H23NO4 | 详情 | 详情 |
| (IV) | 64986 | methyl 4-({2-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]-4-methylpentanoyl}amino)-2-({[(phenylmethyl)oxy]carbonyl}amino)butanoate | C25H39N3O7 | 详情 | 详情 | |
| (V) | 64987 | methyl 2-amino-4-({2-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]-4-methylpentanoyl}amino)butanoate | C17H33N3O5 | 详情 | 详情 | |
| (VI) | 64988 | phenylmethyl 2-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-1-pyrrolidinecarboxylate | C17H18N2O6 | 详情 | 详情 | |
| (VII) | 64989 | phenylmethyl 2-[9,12,12-trimethyl-3-[(methyloxy)carbonyl]-8-(2-methylpropyl)-7,10-dioxo-11-oxa-2,6,9-triazatridec-1-anoyl]-1-pyrrolidinecarboxylate | C30H46N4O8 | 详情 | 详情 | |
| (VIII) | 64990 | phenylmethyl 2-[({3-{[4-methyl-2-(methylamino)pentanoyl]amino}-1-[(methyloxy)carbonyl]propyl}amino)carbonyl]-1-pyrrolidinecarboxylate | C25H38N4O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)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.
| 【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 |