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【结 构 式】 
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【分子编号】52529 【品名】1,1-dimethylethyl 2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propylcarbamate 【CA登记号】 |
【 分 子 式 】C35H47N3O3 【 分 子 量 】557.7766 【元素组成】C 75.37% H 8.49% N 7.53% O 8.61% |
合成路线1
该中间体在本合成路线中的序号：(XVII)The (S)-methyl tryptamine (XIII) was protected as the N-Boc derivative (XIV), and its ethyl ester group was then hydrolyzed with KOH to provide acid (XV). Coupling of (XV) with isoquinuclidine (XVI) in the presence of PyBOP gave amide (XVII). Cleavage of the N-Boc group of (XVII) was carried out employing trifluoroacetic acid in anisole. The resultant amine (XVIII) was condensed with 2,4-dinitrobenzenesulfonyl chloride (XIX) under modified Schotten-Baumann conditions to afford the sulfonamide (XX). Mitsunobu coupling of sulfonamide (XX) with 4-(2-hydroxyethyl)pyridine (XXI) gave adduct (XXII). The sulfonyl group of (XXII) was finally removed by treatment with neat propylamine to yield the title secondary amine.
| 【1】 Ashton, W.T.; et al.; Orally, bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity. Bioorg Med Chem Lett 2001, 11, 19, 2597. |
| 【2】 Chu, L.; Wyvratt, M.J.; Ponpipom, M.M.; Lin, P.; Ashton, W.T.; Goulet, M.; Young, J.; Girotra, N.N.; Fisher, M.H. (Merck & Co., Inc.); Antagonists of gonadotropin releasing hormone. EP 1095038; WO 0004013 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 52525 | ethyl 2-[3-(2-amino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoate | C25H32N2O2 | 详情 | 详情 | |
| (XIV) | 52526 | ethyl 2-[3-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-methylethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoate | C30H40N2O4 | 详情 | 详情 | |
| (XV) | 52527 | 2-[3-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-methylethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoic acid | C28H36N2O4 | 详情 | 详情 | |
| (XVI) | 52528 | 2-azabicyclo[2.2.2]octane | C7H13N | 详情 | 详情 | |
| (XVII) | 52529 | 1,1-dimethylethyl 2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propylcarbamate | C35H47N3O3 | 详情 | 详情 | |
| (XVIII) | 52530 | 2-[3-(2-amino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(2-azabicyclo[2.2.2]oct-2-yl)-2-methyl-1-propanone | C30H39N3O | 详情 | 详情 | |
| (XIX) | 52531 | 2,4-dinitrobenzenesulfonyl chloride | C6H3ClN2O6S | 详情 | 详情 | |
| (XX) | 52532 | N-{2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl}-2,4-dinitrobenzenesulfonamide | C36H41N5O7S | 详情 | 详情 | |
| (XXI) | 52533 | 2-(4-Pyridinyl)-1-ethanol; 2-Pyridin-4-ylethanol | C7H9NO | 详情 | 详情 | |
| (XXII) | 52534 | N-{2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl}-2,4-dinitro-N-[2-(4-pyridinyl)ethyl]benzenesulfonamide | C43H48N6O7S | 详情 | 详情 |