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【结 构 式】 
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【分子编号】27114 【品名】phenyl(1-[2-[4-(4-piperidinyloxy)-2-(2,2,2-trifluoroethoxy)phenyl]acetyl]-4-piperidinyl)formamide 【CA登记号】 |
【 分 子 式 】C27H32F3N3O4 【 分 子 量 】519.5641096 【元素组成】C 62.42% H 6.21% F 10.97% N 8.09% O 12.32% |
合成路线1
该中间体在本合成路线中的序号：(XIV)Regioselective Mitsunobu condensation of 2',4'-dihydroxyacetophenone (VII) with N-Boc-4-piperidinol (VIII) afforded ether (IX). The 2'-hydroxyl group of (IX) was then alkylated with 2,2,2-trifluoroethyl trifluoromethanesulfonate in the presence of Cs2CO3 to give (X). Oxidative rearrangement of the acetophenone (X) employing thallium trinitrate and trimethyl orthoformate generated the phenylacetic ester (XI), which was hydrolyzed to acid (XII) with NaOH in aqueous MeOH. Subsequent EDC-mediated coupling of (XII) with piperidine intermediate (VI) yielded amide (XIII). The N-Boc group of (XIII) was cleaved using HCl in EtOAc, and the secondary amine (XIV) was acylated with acetic anhydride in the presence of diisopropyl ethylamine to afford the target acetamide.
| 【1】 Bock, M.G.; Evans, B.E.; Williams, P.D.; et al.; Nonpeptide oxytocin antagonists: Analogs of L-371,257 with improved potency. Bioorg Med Chem Lett 1999, 9, 9, 1311. |
| 【2】 Freidinger, R.M.; Stauffer, K.; Perlow, D.S.; Sparks, M.A.; Williams, P.D.; Bell, I.M. (Merck & Co., Inc.); Tocolytic oxytocin receptor antagonists. GB 2326410; US 6090805 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 40675 | 2,2,2-trifluoroethyl trifluoromethanesulfonate | 6226-25-1 | C3H2F6O3S | 详情 | 详情 | |
| (VI) | 19420 | 1-(4-piperidinyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one | C13H16N2O2 | 详情 | 详情 | |
| (VII) | 13961 | Resacetophenone; 1-(2,4-Dihydroxyphenyl)-1-ethanone | 89-84-9 | C8H8O3 | 详情 | 详情 |
| (VIII) | 18625 | tert-butyl 4-hydroxy-1-piperidinecarboxylate | C10H19NO3 | 详情 | 详情 | |
| (X) | 27110 | tert-butyl 4-[4-acetyl-3-(2,2,2-trifluoroethoxy)phenoxy]-1-piperidinecarboxylate | C20H26F3NO5 | 详情 | 详情 | |
| (XI) | 27111 | tert-butyl 4-[4-(2-methoxy-2-oxoethyl)-3-(2,2,2-trifluoroethoxy)phenoxy]-1-piperidinecarboxylate | C21H28F3NO6 | 详情 | 详情 | |
| (XII) | 27112 | 2-[4-[[1-(tert-butoxycarbonyl)-4-piperidinyl]oxy]-2-(2,2,2-trifluoroethoxy)phenyl]acetic acid | C20H26F3NO6 | 详情 | 详情 | |
| (XIII) | 27113 | tert-butyl 4-[4-(2-oxo-2-[4-[2-oxo-2H-3,1-benzoxazin-1(4H)-yl]-1-piperidinyl]ethyl)-3-(2,2,2-trifluoroethoxy)phenoxy]-1-piperidinecarboxylate | C33H40F3N3O7 | 详情 | 详情 | |
| (XIV) | 27114 | phenyl(1-[2-[4-(4-piperidinyloxy)-2-(2,2,2-trifluoroethoxy)phenyl]acetyl]-4-piperidinyl)formamide | C27H32F3N3O4 | 详情 | 详情 |