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【结 构 式】 
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【分子编号】32111 【品名】tert-butyl (4S)-4-[3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxopropyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 【CA登记号】 |
【 分 子 式 】C23H32N2O6 【 分 子 量 】432.51696 【元素组成】C 63.87% H 7.46% N 6.48% O 22.19% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Pyrrolidinone (XXVI): The selective hydrolysis of the known methyl ester (XIV) with NaOH in methanol/water gives the corresponding carboxylic acid (XV), which is coupled with the chiral oxazolidinone (XVI) by means of pivaloyl chloride and Et3N in THF to yield the amide (XVII). The regiocontrolled alkylation of (XVII) with allyl iodide and NaN(SiMe3)2 in THF affords the allyl derivative (XVIII), which is submitted to ozonolysis in dichloromethane to provide the aldehyde (XIX). The condensation of (XIX) with 2,4-dimethoxybenzylamine (XX) yields imine (XXI), which by a reductive cyclization with NaBH3CN in THF/EtOH affords pyrrolidinone (XXII). Cleavage of the oxazolidine ring of (XXII) with TsOH in hot methanol gives the amino alcohol (XXIII), which is oxidized with oxalyl chloride in DMSO to the aldehyde (XXIV). Finally, this compound is condensed with triethyl phosphonoacetate (XXV) by means of NaN(SiMe3)2 in THF to provide the desired pyrrolidinone (XXVI).
| 【1】 Dragovich, P.S.; Prins, T.J.; Zhou, R.; et al.; Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements. J Med Chem 1999, 42, 7, 1213. |
| 【2】 Graul, A.; Castañer, J.; AG-7088. Drugs Fut 2000, 25, 1, 9. |
| 【3】 Meyer, M.D.; Daanen, J.F.; Ehrlich, P.P.; Ralston, J.W. (Abbott Laboratories Inc.); 3-Phenylpyrrole alpha-1 adrenergic cpds.. WO 9957122 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 32112 | 3-iodo-1-propene;3-iodo-propen;allyl iodide | 556-56-9 | C3H5I | 详情 | 详情 | |
| (XIV) | 32109 | tert-butyl (4S)-4-(3-methoxy-3-oxopropyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C14H25NO5 | 详情 | 详情 | |
| (XV) | 32110 | 3-[(4S)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]propionic acid | C13H23NO5 | 详情 | 详情 | |
| (XVI) | 14694 | (S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone | 90719-32-7 | C10H11NO2 | 详情 | 详情 |
| (XVII) | 32111 | tert-butyl (4S)-4-[3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxopropyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C23H32N2O6 | 详情 | 详情 | |
| (XVIII) | 32113 | tert-butyl (4S)-4-((2S)-2-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-4-pentenyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C26H36N2O6 | 详情 | 详情 | |
| (XIX) | 32114 | tert-butyl (4S)-4-((2R)-2-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-4-oxobutyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C25H34N2O7 | 详情 | 详情 | |
| (XX) | 32115 | (2,4-dimethoxyphenyl)methanamine; 2,4-dimethoxybenzylamine | 20781-21-9 | C9H13NO2 | 详情 | 详情 |
| (XXI) | 32116 | tert-butyl (4S)-4-[(2R)-2-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-4-[(2,4-dimethoxybenzyl)imino]butyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C34H45N3O8 | 详情 | 详情 | |
| (XXII) | 32117 | tert-butyl (4S)-4-[[(3S)-1-(2,4-dimethoxybenzyl)-2-oxopyrrolidinyl]methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C24H36N2O6 | 详情 | 详情 | |
| (XXIII) | 32118 | tert-butyl (1S)-2-[(3S)-1-(2,4-dimethoxybenzyl)-2-oxopyrrolidinyl]-1-(hydroxymethyl)ethylcarbamate | C21H32N2O6 | 详情 | 详情 | |
| (XXIV) | 32119 | tert-butyl (1S)-2-[(3S)-1-(2,4-dimethoxybenzyl)-2-oxopyrrolidinyl]-1-formylethylcarbamate | C21H30N2O6 | 详情 | 详情 | |
| (XXV) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (XXVI) | 32105 | ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-5-[(3S)-1-(2,4-dimethoxybenzyl)-2-oxopyrrolidinyl]-2-pentenoate | C25H36N2O7 | 详情 | 详情 |