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【结 构 式】 
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【分子编号】68895 【品名】(2R,3S,4R,6S)-2-(((3aR,4S,7R,9S,10S,11S,13S,15S,15aS)-1-(4-(4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl)butyl)-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-10-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate 【CA登记号】 |
【 分 子 式 】C50H69FN6O11 【 分 子 量 】949.13 【元素组成】C 63.27% H 7.33% F 2.00% N 8.85% O 18.54% |
合成路线1
该中间体在本合成路线中的序号：(X)Fluorination of the keto intermediate (VII) is accomplished with potassium tert-butoxide and N-fluo-robenzenesulfonamide (NFSI) in THF/CH2Cl2 at –20 °C to –15 °C to afford the fluoro-azide intermediate (VIII). The triazole intermediate (X) is prepared by a copper-catalyzed azide-alkyne cycloaddition reaction between the fluoro-azide intermediate (VIII) and 3-ethynylaniline (IX) in the presence of copper(I) iodide and DIEA in acetonitrile. Deprotection of the triazole intermediate (X) is accomplished by refluxing in methanol to yield solithromycin . 4-Azidobutylamine (XIII) is prepared by substitution of 1,4-dibromobutane (XI) with sodium azide in DMF/H2O at 80 °C to produce 1,4-diazidobutane (XII), which, without isolation, is subjected to partial reduction with triphenylphosphine in MTBE to afford 4-azidobutylamine (XIII) .
| 【1】 Hwang, C., Duffield, J., Chiu, Y. et al. SAR of 11,12-carbamate macrolides/ketolides linked with 1,4-substituted-[1,2,3]-triazoles. 48th Intersci Conf Antimicrob Agents Chemother/Infect Dis Soc Am 46th Annu Meet (Oct 25-28, Washington, DC) 2008, Abst F1-3973. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 68893 | (2R,3S,4R,6S)-2-(((3aR,4S,7S,9S,10S,11S,13S,15S,15aS)-1-(4-azidobutyl)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-10-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C42H63N5O11 | 详情 | 详情 | |
| (VIII) | 68894 | (2R,3S,4R,6S)-2-(((3aR,4S,7R,9S,10S,11S,13S,15S,15aS)-1-(4-azidobutyl)-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-10-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C42H62FN5O11 | 详情 | 详情 | |
| (IX) | 56445 | 3-Aminophenylacetylene; 3-Ethynylaniline; m-Aminophenylacetylene | 54060-30-9 | C8H7N | 详情 | 详情 |
| (X) | 68895 | (2R,3S,4R,6S)-2-(((3aR,4S,7R,9S,10S,11S,13S,15S,15aS)-1-(4-(4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl)butyl)-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-10-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C50H69FN6O11 | 详情 | 详情 |