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【结 构 式】 
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【分子编号】50963 【品名】3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-amine; 3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-ylamine 【CA登记号】 |
【 分 子 式 】C13H12FNO2S 【 分 子 量 】265.3082232 【元素组成】C 58.85% H 4.56% F 7.16% N 5.28% O 12.06% S 12.09% |
合成路线1
该中间体在本合成路线中的序号：(XI)The cyclization of 3-bromophenylhydrazine (I) with 1,1,1-trifluoropentane-2,4-dione (II) in refluxing acetic acid gives an inseparable regioisomeric mixture of pyrazoles (III) + (IV), which is treated with CuCN in refluxing NMP to yield the mixture of benzonitriles (V) + (VI). The reaction of this mixture with NBS in CCl4 affords the mixture of bromomethyl compounds (VII) + (VIII), which is treated with CaCO3 in dioxane/water to provide a mixture of hydroxymethyl compounds that is easily separated by chromatography. The desired hydroxymethyl pyrazole (IX) is oxidized with NaIO4 and RuCl3 to give the carboxylic acid (X), which is condensed with 3-fluoro-2'-(methylsulfonyl)biphenyl-4-amine (XI) by means of oxalyl chloride and DMAP in dichloromethane to yield the carboxamide (XII). Finally, the cyano group of (XII) is hydrogenated with H2 over Pd/C in methanol/HOAc.
| 【1】 Pinto, D.J.P.; Orwat, M.J.; Wang, S.; et al.; Discovery of 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'(methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally biovailable inhibitor of blood coagulation factor Xa. J Med Chem 2001, 44, 4, 566. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 37812 | 1-(3-bromophenyl)hydrazine | 27246-81-7 | C6H7BrN2 | 详情 | 详情 |
| (II) | 46384 | 1,1,1-trifluoro-2,4-pentanedione | C5H5F3O2 | 详情 | 详情 | |
| (III) | 46386 | 1-(3-bromophenyl)-3-methyl-5-(trifluoromethyl)-1H-pyrazole | C11H8BrF3N2 | 详情 | 详情 | |
| (IV) | 46385 | 1-(3-bromophenyl)-5-methyl-3-(trifluoromethyl)-1H-pyrazole | C11H8BrF3N2 | 详情 | 详情 | |
| (V) | 50961 | 3-[3-methyl-5-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile | C12H8F3N3 | 详情 | 详情 | |
| (VI) | 46387 | 3-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile | C12H8F3N3 | 详情 | 详情 | |
| (VII) | 50962 | 3-[3-(bromomethyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile | C12H7BrF3N3 | 详情 | 详情 | |
| (VIII) | 46388 | 3-[5-(bromomethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile | C12H7BrF3N3 | 详情 | 详情 | |
| (IX) | 46389 | 3-[5-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile | C12H8F3N3O | 详情 | 详情 | |
| (X) | 46390 | 1-(3-cyanophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid | C12H6F3N3O2 | 详情 | 详情 | |
| (XI) | 50963 | 3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-amine; 3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-ylamine | C13H12FNO2S | 详情 | 详情 | |
| (XII) | 46395 | 1-(3-cyanophenyl)-N-[3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide | C25H16F4N4O3S | 详情 | 详情 |