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【结 构 式】 
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【分子编号】57035 【品名】N-{2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl}-1-(3-fluoro-2-naphthyl)-3-methyl-1H-pyrazole-5-carboxamide 【CA登记号】 |
【 分 子 式 】C31H29FN4O3S 【 分 子 量 】556.6608232 【元素组成】C 66.89% H 5.25% F 3.41% N 10.06% O 8.62% S 5.76% |
合成路线1
该中间体在本合成路线中的序号：(XV)Addition of triisopropyl borate to the ortho-lithiated derivative of N-tert-butyl benzenesulfonamide (XI), followed by acid aqueous work-up, gives rise to the boronic acid (XII). Subsequent Suzuki coupling between (XII) and 4-bromoaniline (XIII) affords the biphenyl sulfonamide (XIV). Then, trimethylaluminum-catalyzed condensation of the pyrazole ester (X) with the biphenyl amine (XIV) generates amide (XV). The N-tert-butyl protecting group of (XV) is finally cleaved with trifluoroacetic acid to furnish the title compound.
| 【1】 Jia, Z.J.; et al.; Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors: Part 1: Structure-activity relationships of the substituted 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides. Bioorg Med Chem Lett 2002, 12, 12, 1651. |
| 【2】 Wang, L.; Zhu, B.-Y.; Li, W.; Zhang, P.; Huang, W.; Song, Y.; Goldman, E.; Zuckett, J.; Scarborough, R. (Millennium Pharmaceuticals, Inc.); Benzamides and related inhibitors of factor Xa. EP 1216228; EP 1216231; WO 0119788; WO 0119798 . |
| 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) | 57034 | ethyl 1-(3-fluoro-2-naphthyl)-3-methyl-1H-pyrazole-5-carboxylate | C17H15FN2O2 | 详情 | 详情 | |
| (XI) | 26626 | N-(tert-butyl)benzenesulfonamide | C10H15NO2S | 详情 | 详情 | |
| (XII) | 26627 | 2-[(tert-butylamino)sulfonyl]phenylboronic acid | C10H16BNO4S | 详情 | 详情 | |
| (XIII) | 22531 | 4-Bromoaniline; 4-Bromophenylamine | 106-40-1 | C6H6BrN | 详情 | 详情 |
| (XIV) | 23363 | 4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide | C16H20N2O2S | 详情 | 详情 | |
| (XV) | 57035 | N-{2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl}-1-(3-fluoro-2-naphthyl)-3-methyl-1H-pyrazole-5-carboxamide | C31H29FN4O3S | 详情 | 详情 |