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【结 构 式】 
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【分子编号】54037 【品名】tert-butyl (2S)-1-({(2-cyclopentylethyl)[2-(2-hydroxyethoxy)-2-oxoethyl]amino}carbonyl)-2-pyrrolidinecarboxylate 【CA登记号】 |
【 分 子 式 】C21H36N2O6 【 分 子 量 】412.52672 【元素组成】C 61.14% H 8.8% N 6.79% O 23.27% |
合成路线1
该中间体在本合成路线中的序号：(XI)The condensation of ArgoGel-OH resin (I) with N-(Fmoc)-glycine (II) by means of DIC and DMAP gives the resin-bound Fmoc-glycine (III), which is deprotected with piperidine to yield the resin-bound glycine (IV). The reaction of (IV) with 2-nitrophenylsulfonyl chloride (V) affords the sulfonamide (VI), which is alkylated with 2-cyclopentylethanol (VII) by means of DIAD and PPh3 to provide the N-alkylated sulfonamide (VIII). The reaction of (VIII) with Ph-SH, DBU and pyridine gives the N-alkylated resin-bound glycine (IX), which is condensed with 1-(chlorocarbonyl)-L-proline tert-butyl ester (X) to yield the resin-bound dipeptide tert-butyl ester (XI). Hydrolysis of the ester group of (XI) with TFA affords the free resin-bound dipeptide (XII), which is condensed with 4,5-dimethylthiazole-2-amine (XIII) by means of PyBOP and DMAP to provide the corresponding prolinamide (XIV). Finally, this compound is treated with hydroxylamine in order to cleave the title compound from the resin by formation of the desired hydroxamic acid.
| 【1】 Lewis, J.G.; Wu, C.; Jacobs, J.; et al.; Iterative parallel synthesis-derived N-alkyl urea hydroxamic acids: A new class of peptide deformylase inhibitors. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-358. |
| 【2】 Patel, D.V.; Jacobs, J.W.; Lewis, J.; Ni, Z.-J. (Versicor, Inc.); Novel urea cpds., compsns. and methods of use and preparation. WO 0144178 . |
| 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) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (II) | 42131 | 2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid | 29022-11-5 | C17H15NO4 | 详情 | 详情 |
| (III) | 54030 | 2-hydroxyethyl 2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}acetate | C19H19NO5 | 详情 | 详情 | |
| (IV) | 54031 | 2-hydroxyethyl 2-aminoacetate | C4H9NO3 | 详情 | 详情 | |
| (V) | 32624 | 2-Nitrobenzenesulfonyl chloride | 1694-92-4 | C6H4ClNO4S | 详情 | 详情 |
| (VI) | 54032 | 2-hydroxyethyl 2-{[(2-nitrophenyl)sulfonyl]amino}acetate | C10H12N2O7S | 详情 | 详情 | |
| (VII) | 54033 | 2-Cyclopentylethanol; 2-Hydroxyethylcyclopentane; alpha-Methylcyclopentanemethanol; Cyclopentylmethylcarbinol | 766-00-7 | C7H14O | 详情 | 详情 |
| (VIII) | 54034 | 2-hydroxyethyl 2-{(2-cyclopentylethyl)[(2-nitrophenyl)sulfonyl]amino}acetate | C17H24N2O7S | 详情 | 详情 | |
| (IX) | 54035 | 2-hydroxyethyl 2-[(2-cyclopentylethyl)amino]acetate | C11H21NO3 | 详情 | 详情 | |
| (X) | 54036 | tert-butyl (2S)-1-(chlorocarbonyl)-2-pyrrolidinecarboxylate | C10H16ClNO3 | 详情 | 详情 | |
| (XI) | 54037 | tert-butyl (2S)-1-({(2-cyclopentylethyl)[2-(2-hydroxyethoxy)-2-oxoethyl]amino}carbonyl)-2-pyrrolidinecarboxylate | C21H36N2O6 | 详情 | 详情 | |
| (XII) | 54038 | (2S)-1-({(2-cyclopentylethyl)[2-(2-hydroxyethoxy)-2-oxoethyl]amino}carbonyl)-2-pyrrolidinecarboxylic acid | C17H28N2O6 | 详情 | 详情 | |
| (XIII) | 54039 | 4,5-dimethyl-1,3-thiazol-2-ylamine; 4,5-dimethyl-1,3-thiazol-2-amine | C5H8N2S | 详情 | 详情 | |
| (XIV) | 54040 | 2-hydroxyethyl 2-{(2-cyclopentylethyl)[((2S)-2-{[(4,5-dimethyl-1,3-thiazol-2-yl)amino]carbonyl}pyrrolidinyl)carbonyl]amino}acetate | C22H34N4O5S | 详情 | 详情 |