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【结 构 式】 
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【分子编号】68274 【品名】racemic ethyl 3-(6-(diisopropylcarbamoyl)naphthalen-2-yl)-3-hydroxy-3-(1-trityl-1H-imidazol-4-yl)propanoate 【CA登记号】 |
【 分 子 式 】C44H45N3O4 【 分 子 量 】679.859 【元素组成】C 77.73% H 6.67% N 6.18% O 9.41% |
合成路线1
该中间体在本合成路线中的序号：(XXII)Alternatively, racemate (XIX) is obtained by aldol condensation of ketone (VI) with ethyl acetate (XIII) by means of LDA to yield the racemic β-hydroxy ester (XXII), which by reduction with Red-Al in toluene furnishes the corresponding diol (XXIII). Activation of diol (XXIII) with MsCl in the presence of DIEA in THF followed by cyclization by means of DIEA and MeOH in acetonitrile gives the 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol derivative (XXIV). Finally, the N,N-diisopropyl-2-naphthamide derivative (XXVI) is treated with CH3NH2 in the presence of BuLi in THF .
| 【1】 Kaku, T., Hitaka, T., Ojida, A. et al. Discovery of TAK-700, a naphthylmethylimidazole derivative, as a highly selective, orally active 17, 20 lyase inhibitor for prostate cancer. 240th ACS Natl Meet (Aug 22-26, Boston) 2010, Abst MEDI 96. |
| 【2】 Hitaka, T., Kusaka, M., Aoki, I., Ojida, A., Matsunaga, N., Adachi, M., Tasaka, A. (Takeda Pharmaceutical Co., Ltd.). Novel imidazole derivatives, production method thereof and use thereof. EP 1334106, EP 1681290, JP 2003201282, JP 2006045239, US 7141598, WO 2002040484. |
| 【3】 Kaku, T., Hitaka, T., Ojida, A. et al. Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem 2011, 19(21): 6383-99. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 68258 | N,N-diisopropyl-6-(1-trityl-1H-imidazole-4-carbonyl)-2-naphthamide | C40H37N3O2 | 详情 | 详情 | |
| (XIII) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (XIX) | 68271 | 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol;6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide | C18H17N3O2 | 详情 | 详情 | |
| (XXII) | 68274 | racemic ethyl 3-(6-(diisopropylcarbamoyl)naphthalen-2-yl)-3-hydroxy-3-(1-trityl-1H-imidazol-4-yl)propanoate | C44H45N3O4 | 详情 | 详情 | |
| (XXIII) | 68275 | 6-(1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl)-N,N-diisopropyl-2-naphthamide (XXIV) C23H27N3O2 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol | C42H43N3O3 | 详情 | 详情 | |
| (XXIV) | 68276 | 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N,N-diisopropyl-2-naphthamide | C23H27N3O2 | 详情 | 详情 |