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【结 构 式】 
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【分子编号】43289 【品名】diethyl 4-((2S)-2-(acetamido)-3-[[(5S)-3-(aminocarbonyl)-2-(cyclohexylmethoxy)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-yl]amino]-3-oxopropyl)-2-(diethoxyphosphoryl)phenylphosphonate 【CA登记号】 |
【 分 子 式 】C38H57N3O10P2 【 分 子 量 】777.832324 【元素组成】C 58.68% H 7.39% N 5.4% O 20.57% P 7.96% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)Coupling of carboxylic acid (V) with either the racemic amine (XVI) or the chiral amine (XXIV) in the presence of EDC and HOBt, followed by trifluoroacetic acid-promoted cleavage of the Boc group, furnished the diastereomeric mixture of amides (XXV) or the pure (S,S)-isomer (XXVI), respectively. Isomer (XXVI) was also obtained by separation of the diastereomeric mixture (XXV) by means of preparative reverse-phase HPLC. Acetylation of the amino group of (XXVI) with acetic anhydride gave amide (XXVII). Finally, the ethyl phosphonate esters of (XXVII) were hydrolyzed by means of trimethylsilyl iodide in acetonitrile.
| 【1】 Bohacek, R.; Yang, M.; Shakespeare, W.; et al.; Structure-based design of an osteoclast-selective, nonpeptide Src homology 2 inhibitor with in vivo antiresorptive activity. Proceedings of the National Academy of Sciences of the United States of America 2000, 97, 17, 9373. |
| 【2】 Bohacek, R.; Sawyer, T.K.; Yang, M.G.; Eyermann, C.J.; Sundaramoorthi, R.; Shakespeare, W.C. (Ariad Pharmaceuticals Inc.); Bicyclic signal transduction inhibitors, compsns. containing them & uses thereof. WO 0027802 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 43286 | (9S)-9-amino-3-(cyclohexylmethoxy)-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-2-carboxamide | C19H28N2O2 | 详情 | 详情 | |
| (XVI) | 43278 | 9-amino-3-(cyclohexylmethoxy)-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-2-carboxamide | C19H28N2O2 | 详情 | 详情 | |
| (XXIV) | 43268 | (2S)-3-[3,4-bis(diethoxyphosphoryl)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid | C22H37NO10P2 | 详情 | 详情 | |
| (XXV) | 43287 | diethyl 4-((2S)-2-amino-3-[[3-(aminocarbonyl)-2-(cyclohexylmethoxy)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-yl]amino]-3-oxopropyl)-2-(diethoxyphosphoryl)phenylphosphonate | C36H55N3O9P2 | 详情 | 详情 | |
| (XXVI) | 43288 | diethyl 4-((2S)-2-amino-3-[[(5S)-3-(aminocarbonyl)-2-(cyclohexylmethoxy)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-yl]amino]-3-oxopropyl)-2-(diethoxyphosphoryl)phenylphosphonate | C36H55N3O9P2 | 详情 | 详情 | |
| (XXVII) | 43289 | diethyl 4-((2S)-2-(acetamido)-3-[[(5S)-3-(aminocarbonyl)-2-(cyclohexylmethoxy)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-yl]amino]-3-oxopropyl)-2-(diethoxyphosphoryl)phenylphosphonate | C38H57N3O10P2 | 详情 | 详情 |