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【结 构 式】 
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【分子编号】63026 【品名】2-[(4-[1-(tert-butoxycarbonyl)-4-piperidinyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}butanoyl)amino]acetic acid 【CA登记号】 |
【 分 子 式 】C28H49N3O7 【 分 子 量 】539.71308 【元素组成】C 62.31% H 9.15% N 7.79% O 20.75% |
合成路线1
该中间体在本合成路线中的序号：(IX)Condensation of 4-vinylpyridine (I) with diethyl malonate (II) affords the bis(pyridylethyl)malonate (III) which, upon acidic hydrolysis and decarboxylation leads to mono-acid (IV). Catalytic hydrogenation of the pyridine rings of (IV) in the presence of Pd/C furnishes the corresponding piperidinyl compound (V), which is further protected as the N-Boc derivative (VI) employing di-t-butyl dicarbonate. Acid (VI) is coupled to glycine methyl ester (VII) via activation with cyanuric fluoride to yield amide (VIII). Then, alkaline hydrolysis of the methyl ester group provides carboxylic acid (IX).
| 【1】 Lesur, B.; Henry, M.; Yue, C.; Giboulot, T. (Laboratoires L. Lafon); Bispiperidines as antithrombotic agents. EP 1098878; FR 2781223; JP 2002520393; US 6333338; WO 0003986 . |
| 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) | 45857 | 4-vinylpyridine | C7H7N | 详情 | 详情 | |
| (II) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (III) | 63020 | diethyl 2,2-bis[2-(4-pyridinyl)ethyl]malonate | C21H26N2O4 | 详情 | 详情 | |
| (IV) | 63022 | 4-(4-pyridinyl)-2-[2-(4-pyridinyl)ethyl]butanoic acid | C16H18N2O2 | 详情 | 详情 | |
| (V) | 63023 | 4-(4-piperidinyl)-2-[2-(4-piperidinyl)ethyl]butanoic acid | C16H30N2O2 | 详情 | 详情 | |
| (VI) | 63024 | 4-[1-(tert-butoxycarbonyl)-4-piperidinyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}butanoic acid | C26H46N2O6 | 详情 | 详情 | |
| (VII) | 17568 | methyl 2-aminoacetate | C3H7NO2 | 详情 | 详情 | |
| (VIII) | 63025 | tert-butyl 4-(5-[1-(tert-butoxycarbonyl)-4-piperidinyl]-3-{[(2-methoxy-2-oxoethyl)amino]carbonyl}pentyl)-1-piperidinecarboxylate | C29H51N3O7 | 详情 | 详情 | |
| (IX) | 63026 | 2-[(4-[1-(tert-butoxycarbonyl)-4-piperidinyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}butanoyl)amino]acetic acid | C28H49N3O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)After activation of acid (IX) as the mixed anhydride with isobutyl chloroformate, coupling with the mono-protected diaminopropionate (X) leads to amide (XI). Subsequent removal of the N-carbobenzoxy group by catalytic hydrogenolysis gives amino ester (XII). This is then acylated by 2-naphthalenesulfonyl chloride (XIII), yielding sulfonamide (XIV).
| 【1】 Lesur, B.; Henry, M.; Yue, C.; Giboulot, T. (Laboratoires L. Lafon); Bispiperidines as antithrombotic agents. EP 1098878; FR 2781223; JP 2002520393; US 6333338; WO 0003986 . |
| 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) | 63026 | 2-[(4-[1-(tert-butoxycarbonyl)-4-piperidinyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}butanoyl)amino]acetic acid | C28H49N3O7 | 详情 | 详情 | |
| (X) | 26615 | ethyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate | C13H18N2O4 | 详情 | 详情 | |
| (XI) | 63027 | tert-butyl 4-[(10S)-3-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}-10-(ethoxycarbonyl)-4,7,12-trioxo-14-phenyl-13-oxa-5,8,11-triazatetradec-1-yl]-1-piperidinecarboxylate | C41H65N5O10 | 详情 | 详情 | |
| (XII) | 63028 | tert-butyl 4-{3-{[(2-{[(2S)-2-amino-3-ethoxy-3-oxopropyl]amino}-2-oxoethyl)amino]carbonyl}-5-[1-(tert-butoxycarbonyl)-4-piperidinyl]pentyl}-1-piperidinecarboxylate | C33H59N5O8 | 详情 | 详情 | |
| (XIII) | 27989 | 2-naphthalenesulfonyl chloride | 93-11-8 | C10H7ClO2S | 详情 | 详情 |
| (XIV) | 63029 | tert-butyl 4-[5-[1-(tert-butoxycarbonyl)-4-piperidinyl]-3-({[2-({(2S)-3-ethoxy-2-[(2-naphthylsulfonyl)amino]-3-oxopropyl}amino)-2-oxoethyl]amino}carbonyl)pentyl]-1-piperidinecarboxylate | C43H65N5O10S | 详情 | 详情 |