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【结 构 式】 
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【分子编号】39226 【品名】4-[(tert-butoxycarbonyl)amino]butyric acid;4-((tert-butoxycarbonyl)amino)butanoic acid 【CA登记号】57294-38-9 |
【 分 子 式 】C9H17NO4 【 分 子 量 】203.23832 【元素组成】C 53.19% H 8.43% N 6.89% O 31.49% |
合成路线1
该中间体在本合成路线中的序号：(I)4-(tert-Butoxycarbonylamino)butyric acid (I) was activated as the corresponding mixed anhydride (II) by treatment with ethyl chloroformate and triethylamine. Subsequent coupling of (II) with 4-aminopyridine (III) afforded the title amide.
| 【1】 Leoni, A.; Villetti, G.; Morigi, R.; Pietra, C.; Andreani, A.; Locatelli, A.; Rambaldi, M.; 4-Aminopyridine derivatives with antiamnesic activity. Eur J Med Chem 2000, 35, 1, 77. |
合成路线2
该中间体在本合成路线中的序号：(II)Esterification of glucose diacetonide (I) with N-Boc-gamma-aminobutyric acid (II) in the presence of DCC and DMAP provides the protected glucose-3-ester (III). Hydrolysis of (III) with trifluoroacetic acid in CH2Cl2 leads to the 3-GABA-glucose (IV).
| 【1】 Jacob, J.N. (Organomed Corporation); Paclitaxel-carbohydrate conjugates: Design, synthesis and biological evaluations. US 6218367 . |
| 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) | 59011 | (5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol | C12H20O6 | 详情 | 详情 | |
| (II) | 39226 | 4-[(tert-butoxycarbonyl)amino]butyric acid;4-((tert-butoxycarbonyl)amino)butanoic acid | 57294-38-9 | C9H17NO4 | 详情 | 详情 |
| (III) | 59012 | (5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl 4-[(tert-butoxycarbonyl)amino]butanoate | C21H35NO9 | 详情 | 详情 | |
| (IV) | 59013 | (3R,4S,5R,6R)-2,3,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl 4-aminobutanoate | C10H19NO7 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)N-Protection of 4-aminobutyric acid with Boc2O gives N-Boc-4-aminobutyric acid (II) , which by esterification with perphenazine (III) by means of either CDI in DMF or DCC and DMAP in CH2Cl2 affords the N-Boc-amino ester (IV). Alternatively, treatment of N-Boc-GABA (II) with t-BuCOCl in the presence of of Et3N in THF gives the mixed anhydride (V), which by reaction with perphenazine (III) in THF yields amino ester (IV) . Finally, compound (IV) is deprotected by means of MsOH in acetonitrile .
| 【1】 Nudelman, A., Gil-Ad, I., Shpaisman, N. et al. A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects. J Med Chem 2008, 51(9): 2858-62. |
| 【2】 Nudelman, A., Weizman, A., Rephaeli, A., Gil-Ad, I. (Ramot at Tel Aviv University, Ltd.; Bar-Ilan University). Conjugated anti-psychotic drugs and uses thereof. CA 2461663, EP 1429844, EP 2275143, JP 2005503423, JP 2010090170, KR 201009724, WO 2003026563. |
| 【3】 Nudelman, A., Rephaeli, A., Gil-Ad, I., Weizman, A., Halachmi, S., Benjamin, E.J. (Ramot at Tel Aviv University, Ltd.; Bar-Ilan University; BioLineRx, Ltd.). Novel salts of conjugated psychotropic drugs and processes of preparing same. EP 1888120, EP 2272537, JP 2008545777, US 2009298814, WO 2006131923. |
| 【4】 Gil-Ad, I., Rephaeli, A., Weizman, A., Nudelman, A. (Bar-Ilan University; Ramot at Tel Aviv University, Ltd.). Conjugated psychotropic drugs and uses thereof. CA 2560905, EP 1727566, JP 200753029, JP 2011121971, US 2004242570, US 7544681, WO 2005092392. |
| 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) | 13620 | 4-Amino-n-butyric acid; 4-Aminobutyric acid;Piperidinic acid;Piperidic acid | 56-12-2 | C4H9NO2 | 详情 | 详情 |
| (II) | 39226 | 4-[(tert-butoxycarbonyl)amino]butyric acid;4-((tert-butoxycarbonyl)amino)butanoic acid | 57294-38-9 | C9H17NO4 | 详情 | 详情 |
| (III) | 68568 | 2-(4-(3-(2-chloro-10H-phenothiazin-10-yl)propyl)piperazin-1-yl)ethanol | 58-39-9 | C21H26ClN3OS | 详情 | 详情 |
| (IV) | 68569 | 2-(4-(3-(2-chloro-10H-phenothiazin-10-yl)propyl)piperazin-1-yl)ethyl 4-((tert-butoxycarbonyl)amino)butanoate | C30H41ClN4O4S | 详情 | 详情 | |
| (V) | 68570 | 4-((tert-butoxycarbonyl)amino)butanoic pivalic anhydride | C14H25NO5 | 详情 | 详情 |