【结 构 式】 |
【分子编号】26579 【品名】3-hydroxy-3-[4-(methylsulfanyl)phenyl]-2-phenyl-2-[(trimethylsilyl)methyl]propanenitrile 【CA登记号】 |
【 分 子 式 】C20H25NOSSi 【 分 子 量 】355.57614 【元素组成】C 67.56% H 7.09% N 3.94% O 4.5% S 9.02% Si 7.9% |
合成路线1
该中间体在本合成路线中的序号:(IV)Reaction of benzaldehyde (I) with trimethylsilyl cyanide and ZnI2 gave O-trimethylsilyl cyanohydrin (II). Subsequent condensation of (II) with 4-(methylthio)benzaldehyde (III) in the presence of lithium hexamethyldisilazide, followed by quenching of the intermediate (IV) with KHF2 and HCl, provided benzoin (V). This was oxidized either under Swern conditions, or with Bi2O3 in acetic to afford the corresponding benzil (VI). Condensation of (VI) with trifluoroacetaldehyde ethyl hemiacetal (VII) produced imidazole (VIII). Finally, oxidation of the sulfide group of (VIII) with hydrogen peroxide in AcOH provided the target sulfone.
【1】 Barta, T.E.; Collins, P.W.; Weier, R.M.; Stealey, M.A.; Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3443. |
【2】 Weier, R.M.; Collins, P.W.; Stealey, M.A.; Barta, T.E.; Huff, R.M. (Pharmacia Corp.); 4,5-Substd. imidazolyl cpds. for the treatment of inflammation. EP 0772601; US 5620999; WO 9603387 . |
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) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
(II) | 26578 | 2-phenyl-3-(trimethylsilyl)propanenitrile | C12H17NSi | 详情 | 详情 | |
(III) | 18815 | 4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde | 3446-89-7 | C8H8OS | 详情 | 详情 |
(IV) | 26579 | 3-hydroxy-3-[4-(methylsulfanyl)phenyl]-2-phenyl-2-[(trimethylsilyl)methyl]propanenitrile | C20H25NOSSi | 详情 | 详情 | |
(V) | 26580 | 2-hydroxy-2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone | C15H14O2S | 详情 | 详情 | |
(VI) | 26581 | 1-[4-(methylsulfanyl)phenyl]-2-phenyl-1,2-ethanedione | C15H12O2S | 详情 | 详情 | |
(VII) | 26582 | 1-ethoxy-2,2,2-trifluoro-1-ethanol | 433-27-2 | C4H7F3O2 | 详情 | 详情 |
(VIII) | 26583 | methyl 4-[5-phenyl-2-(trifluoromethyl)-1H-imidazol-4-yl]phenyl sulfide | C17H13F3N2S | 详情 | 详情 |