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【结 构 式】 
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【分子编号】61049 【品名】methyl (2S)-2-{[(2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-fluorophenyl)propanoyl]amino}-3-phenylpropanoate 【CA登记号】 |
【 分 子 式 】C27H27FN2O5 【 分 子 量 】478.5202632 【元素组成】C 67.77% H 5.69% F 3.97% N 5.85% O 16.72% |
合成路线1
该中间体在本合成路线中的序号：(IV)In a different strategy, N-Cbz-p-fluorophenylalanine (I) is activated as the mixed anhydride (II) employing isobutyl chloroformate and N-methylmorpholine. Coupling of anhydride (II) with phenylalanine methyl ester (III) leads to the dipeptide ester (IV), which is further treated with methanolic ammonia to produce amide (V). The dipeptide amide (V) is alternatively obtained by direct coupling of mixed anhydride (II) with phenylalanine amide (VI). Hydrogenolysis of the N-Cbz group of (V) in the presence of Pd/C furnishes the deprotected dipeptide (VII).
| 【1】 Franzen, H.M.; Bessidskaia, G.; Abedi, V.; Nilsson, A.; Nilsson, M.; Olsson, L.; Frakefamide, an analgesic tetrapeptide: Development of a pilot-plant-scale process. Org Process Res Dev 2002, 6, 6, 788. |
| 【2】 Franzen, H. (AstraZeneca plc); Process for the preparation of a tetrapeptide. WO 9947548 . |
| 【3】 Nilsson, M.; Ellburg, M.; Franzen, H. (AstraZeneca AB); A process for the preparation of H-Tyr-D-Ala-Phe(F)-Phe-NH2. EP 1212350; JP 2003509437; WO 0119849 . |
| 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) | 61047 | (2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-fluorophenyl)propanoic acid | C17H16FNO4 | 详情 | 详情 | |
| (II) | 61048 | C22H24FNO6 | 详情 | 详情 | ||
| (III) | 12324 | methyl (2R)-2-amino-3-phenylpropanoate | 21685-51-8 | C10H13NO2 | 详情 | 详情 |
| (IV) | 61049 | methyl (2S)-2-{[(2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-fluorophenyl)propanoyl]amino}-3-phenylpropanoate | C27H27FN2O5 | 详情 | 详情 | |
| (V) | 61050 | benzyl (1S)-2-{[(1S)-2-amino-1-benzyl-2-oxoethyl]amino}-1-(4-fluorobenzyl)-2-oxoethylcarbamate | C26H26FN3O4 | 详情 | 详情 | |
| (VI) | 19032 | (2S)-2-amino-3-phenylpropanamide | 5241-58-7 | C9H12N2O | 详情 | 详情 |
| (VII) | 61044 | (2S)-2-amino-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-3-(4-fluorophenyl)propanamide | C18H20FN3O2 | 详情 | 详情 |