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【结 构 式】 
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【分子编号】15744 【品名】N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-2,2,2-trifluoro-N-[2-(1-methyl-1H-indol-2-yl)ethyl]acetamide 【CA登记号】 |
【 分 子 式 】C20H24F3N5O3S 【 分 子 量 】471.5036696 【元素组成】C 50.95% H 5.13% F 12.09% N 14.85% O 10.18% S 6.8% |
合成路线1
该中间体在本合成路线中的序号：(XII)3) Treatment of 2-(1-methylindol-2-yl)ethanamine (X) in dichloromethane with trifluoroacetic anhydride and triethylamine yields the trifluoroacetamide (XI). This is alkylated with the chloromethylimidazole (IV) to give (XII) and then treated with aqueous potassium carbonate to generate the amino derivative (XIII). Finally, the reaction of (XIII) with phosgene and aluminum chloride in methylene chloride effects acylation and cyclization with concomitant removal of the protecting group.
| 【1】 Oxford, A.W.; Hagan, R.M.; Tyers, M.B.; Kilpatrick, G.J.; North, P.C.; GR-68755 Hydrochloride. Drugs Fut 1992, 17, 8, 660. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 15742 | 2-(1-methyl-1H-indol-2-yl)ethylamine; 2-(1-methyl-1H-indol-2-yl)-1-ethanamine | C11H14N2 | 详情 | 详情 | |
| (XI) | 15743 | 2,2,2-trifluoro-N-[2-(1-methyl-1H-indol-2-yl)ethyl]acetamide | C13H13F3N2O | 详情 | 详情 | |
| (XII) | 15744 | N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-2,2,2-trifluoro-N-[2-(1-methyl-1H-indol-2-yl)ethyl]acetamide | C20H24F3N5O3S | 详情 | 详情 | |
| (XIII) | 15745 | N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-N-[2-(1-methyl-1H-indol-2-yl)ethyl]amine; N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-2-(1-methyl-1H-indol-2-yl)-1-ethanamine | C18H25N5O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)4) Treatment of the 2-substituted indole (XII) with iodine and potassium iodide in aqueous solution in the presence of potassium carbonate yields the corresponding 3-iodo derivative (XIV). Hydrolysis of the trifluoroacetyl group with aqueous potassium carbonate gives the amino derivative (XV), which undergoes a palladium-catalyzed carbonylation reaction to form the lactam. Finally, the protecting group is removed with hydrochloric acid.
| 【1】 Oxford, A.W.; Hagan, R.M.; Tyers, M.B.; Kilpatrick, G.J.; North, P.C.; GR-68755 Hydrochloride. Drugs Fut 1992, 17, 8, 660. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 15744 | N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-2,2,2-trifluoro-N-[2-(1-methyl-1H-indol-2-yl)ethyl]acetamide | C20H24F3N5O3S | 详情 | 详情 | |
| (XIV) | 15746 | N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-2,2,2-trifluoro-N-[2-(3-iodo-1-methyl-1H-indol-2-yl)ethyl]acetamide | C20H23F3IN5O3S | 详情 | 详情 | |
| (XV) | 15747 | N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-2-(3-iodo-1-methyl-1H-indol-2-yl)-1-ethanamine; N-[(1-[[(dimethylamino)oxy]sulfinyl]-5-methyl-1H-imidazol-4-yl)methyl]-N-[2-(3-iodo-1-methyl-1H-indol-2-yl)ethyl]amine | C18H24IN5O2S | 详情 | 详情 |