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【结 构 式】 
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【分子编号】45853 【品名】tert-butyl 4-[4-[(2-[[(1S)-1-([[(1R)-2-amino-1-(cyclohexylmethyl)-2-oxoethyl]amino]carbonyl)-3-(benzyloxy)-3-oxopropyl]amino]-2-oxoethyl)(ethyl)amino]-4-oxobutyl]-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C38H59N5O8 【 分 子 量 】713.91536 【元素组成】C 63.93% H 8.33% N 9.81% O 17.93% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Treatment of N-Boc-beta cyclohexylalanine (I) in THF with Et3N, isobutyl chloroformate (IBCF) and NH3/MeOH, followed by reaction with HCl gas, yields beta-cyclohexyl alaninamide hydrochloride (II). Amino acid (II) is then converted into dipeptide (IV) by first coupling with protected L-aspartic acid (III) by means of isopropyl chloroformate (IPCF) and N-methyl piperidine (A) in CH2Cl2, followed by Boc removal with TFA in CH2Cl2. Condensation of (IV) with Boc-protected N-ethylglycine (V) and successive Boc removal are performed under the same conditions as for the synthesis of (IV) to furnish tripeptide (VI). Then (VI) is coupled to carboxylic acid (VII) by means BOPCl and Et3N in CH2Cl2 to afford intermediate (VIII). Finally the target compound is obtained by debenzylation of (VIII) with H2 over Pd/C in MeOH/AcOH, followed by Boc removal with TFA in CH2Cl2.
| 【1】 Molino, B.F.; Klein, S.I.; Czekaj, M.; et al.; Design of a new class of orally active fibrinogen receptor antagonists. J Med Chem 1998, 41, 14, 2492. |
| 【2】 Klein, S.I.; Molino, B.F. (Aventis Pharma SA); Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides. EP 0812205; JP 1997507213; US 5866685; WO 9510295 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 45848 | 1-methylpiperidine | 626-67-5 | C6H13N | 详情 | 详情 |
| (I) | 23050 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropionic acid | C14H25NO4 | 详情 | 详情 | |
| (II) | 45847 | (2S)-2-amino-3-cyclohexylpropanamide | 145232-34-4 | C9H18N2O | 详情 | 详情 |
| (III) | 25219 | (2S)-4-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid | 7536-58-5 | C16H21NO6 | 详情 | 详情 |
| (IV) | 45849 | benzyl (3S)-3-amino-4-[[(1R)-2-amino-1-(cyclohexylmethyl)-2-oxoethyl]amino]-4-oxobutanoate | C20H29N3O4 | 详情 | 详情 | |
| (V) | 45850 | 2-[(tert-butoxycarbonyl)(ethyl)amino]acetic acid | 149794-10-5 | C9H17NO4 | 详情 | 详情 |
| (VI) | 45851 | benzyl (3S)-4-[[(1R)-2-amino-1-(cyclohexylmethyl)-2-oxoethyl]amino]-3-[[2-(ethylamino)acetyl]amino]-4-oxobutanoate | C24H36N4O5 | 详情 | 详情 | |
| (VII) | 45852 | 4-[1-(tert-butoxycarbonyl)-4-piperidinyl]butyric acid | C14H25NO4 | 详情 | 详情 | |
| (VIII) | 45853 | tert-butyl 4-[4-[(2-[[(1S)-1-([[(1R)-2-amino-1-(cyclohexylmethyl)-2-oxoethyl]amino]carbonyl)-3-(benzyloxy)-3-oxopropyl]amino]-2-oxoethyl)(ethyl)amino]-4-oxobutyl]-1-piperidinecarboxylate | C38H59N5O8 | 详情 | 详情 |