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【结 构 式】 
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【分子编号】53300 【品名】4-[(2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholinyl]-N,N-dimethyl-2-butynamide 【CA登记号】n/a |
【 分 子 式 】C26H25F7N2O3 【 分 子 量 】546.4850024 【元素组成】C 57.14% H 4.61% F 24.34% N 5.13% O 8.78% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)From the intermediate morpholine (XVIII) the title compound was obtained by several routes. Alkylation of (XVIII) with propargyl bromide (XXXI) gave the N-propargyl morpholine (XXXII). Palladium-catalyzed addition of N,N-dimethylcarbamoyl chloride to the propargyl group of (XXXII) produced the butynamide derivative (XXXIII). The target triazole system (XXXIV) was obtained by dipolar cycloaddition of NaN3 to the acetylenic triple bond of (XXXIII) in hot DMSO. Finally, amide reduction in (XXXIV) with LiAlH4 led to the title dimethylaminomethyl triazole, which was isolated as the hydrochloride salt.
| 【1】 Baker, R.; Harrison, T.; Mcleod, A.M.; Owens, A.P.; Seward, E.M.; Swain, C.J.; Teall, M.R. (Merck Sharp & Dohme Ltd.); Substd. morpholine derivs. and their use as therapeutic agents. EP 0737192; EP 1099702; JP 1997507484; JP 2000219629; US 5612337; WO 9518124 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 18293 | (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-3-(4-fluorophenyl)morpholinyl ether; (2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-fluorophenyl)morpholine | 171482-05-6 | C20H18F7NO2 | 详情 | 详情 |
| (XXXI) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (XXXII) | 53299 | (2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)-4-(2-propynyl)morpholine; (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-3-(4-fluorophenyl)-4-(2-propynyl)morpholinyl ether | n/a | C23H20F7NO2 | 详情 | 详情 |
| (XXXIII) | 53300 | 4-[(2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholinyl]-N,N-dimethyl-2-butynamide | n/a | C26H25F7N2O3 | 详情 | 详情 |
| (XXXIV) | 53301 | 4-{[(2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholinyl]methyl}-N,N-dimethyl-1H-1,2,3-triazole-5-carboxamide | n/a | C26H26F7N5O3 | 详情 | 详情 |