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【结 构 式】 
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【药物名称】LY-339687 【化学名称】4-(1-Ethylpropylidene)-L-glutamic acid 【CA登记号】 【 分 子 式 】C10H17NO4 【 分 子 量 】215.25129 |
【开发单位】Lilly (Originator), NPS Allelix (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Kainate Agonists |
合成路线1
Treatment of ethyl N-Boc-(S)-pyroglutamate (I) with lithium hexamethyldisilazide in THF at -78 C, followed by aldol condensation of the resulting lithium enolate with 3-pentanone (II) in the presence of boron trifluoride etherate, furnished adduct (III). Dehydration of the alcohol group of (III) to produce olefin (IV) was achieved by treatment of (III) with methanesulfonyl chloride and triethylamine. Hydrolysis of the ester and lactam groups of (IV) by means of LiOH afforded diacid (V). The N-Boc group of (V) was finally cleaved with HCl in EtOH.
| 【1】 Bleakman, D.; Ezquerra, J.; Baker, S.R.; et al.; 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett 2000, 10, 16, 1807. |
| 【2】 Rubio Esteban, A.; Pedregal Tercero, C. (Lilly SA); Glutamic acid derivs. and pharmaceutical compsns. for the treatment of central nervous system disorders. EP 0867430; ES 2133095; JP 1998279542 . |
| 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) | 43914 | 1-(tert-butyl) 2-ethyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate | 144978-35-8 | C12H19NO5 | 详情 | 详情 |
| (II) | 32415 | Propione; Dimethylacetone; Diethyl ketone; 3-Pentanone | 96-22-0 | C5H10O | 详情 | 详情 |
| (III) | 43918 | 1-(tert-butyl) 2-ethyl (2S)-4-(1-ethyl-1-hydroxypropyl)-5-oxo-1,2-pyrrolidinedicarboxylate | C17H29NO6 | 详情 | 详情 | |
| (IV) | 43919 | 1-(tert-butyl) 2-ethyl (2S)-4-(1-ethylpropylidene)-5-oxo-1,2-pyrrolidinedicarboxylate | C17H27NO5 | 详情 | 详情 | |
| (V) | 43920 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-(1-ethylpropylidene)pentanedioic acid | C15H25NO6 | 详情 | 详情 |