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【结 构 式】 
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【药物名称】LY-503429 【化学名称】N-[2(S)-Fluoro-2-[3'-(methylsulfonamido)biphenyl-4-yl]propyl]propane-2-sulfonamide 【CA登记号】305446-95-1 (enantiomer), 305447-00-1 (enantiomer), 305447-26-1 (undefined isomer) 【 分 子 式 】C19H25FN2O4S2 【 分 子 量 】428.5485 |
【开发单位】Lilly (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, AMPA Receptor Modulators |
合成路线1
Addition of cyanotrimethylsilane to 4'-iodoacetophenone (I) provided the O-silylated cyanohydrin (II), which was subsequently reduced to the amino alcohol (III) employing borane-dimethyl sulfide complex. Acylation of (III) with 2-propanesulfonyl chloride gave sulfonamide (IV). The hydroxyl group of (IV) was then fluorinated by means of diethylaminosulfur trifluoride, and the resultant racemic fluoride was resolved by chiral HPLC. Finally, Suzuki coupling of the required (S)-enantiomer (V) with boronic ester (VI) yielded the title biphenyl derivative.
| 【1】 Jones, W.D.; Mitchell, D.; Fray, A.H.; Miller, W.D.; Cantrell, B.E.; Bender, D.M.; Zimmerman, D.M.; Simon, R.L.; Zarrinmayeh, H. (Eli Lilly and Company); Monofluoroalkyl derivs.. EP 1183232; WO 0066546 . |
| 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) | 51497 | 4'-Iodoacetophenone; 4-Iodoacetophenone; 1-(4-Iodophenyl)ethanone | 13329-40-3 | C8H7IO | 详情 | 详情 |
| (II) | 51498 | 2-(4-iodophenyl)-2-[(trimethylsilyl)oxy]propanenitrile | C12H16INOSi | 详情 | 详情 | |
| (III) | 51499 | 1-amino-2-(4-iodophenyl)-2-propanol | C9H12INO | 详情 | 详情 | |
| (IV) | 51500 | N-[2-hydroxy-2-(4-iodophenyl)propyl]-2-propanesulfonamide | C12H18INO3S | 详情 | 详情 | |
| (V) | 51501 | N-[(2S)-2-fluoro-2-(4-iodophenyl)propyl]-2-propanesulfonamide | C12H17FINO2S | 详情 | 详情 | |
| (VI) | 51502 | N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanesulfonamide | C13H20BNO4S | 详情 | 详情 |