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【结 构 式】 
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【药物名称】LS-4559 【化学名称】N-(3-Fluorobenzyl)-N-[2-(4'-hydroxybiphenyl-4-yloxy)ethyl]-N'-methylurea 【CA登记号】 【 分 子 式 】C23H23FN2O3 【 分 子 量 】394.44976 |
【开发单位】Pfizer (Originator) 【药理作用】ONCOLYTIC DRUGS, Antimitotic Drugs, Microtubule-Stabilizing Agents |
合成路线1
The alkylation of 4,4'-dihydroxybiphenyl (I) with ethyl bromoacetate (II) in the presence of sodium methoxide afforded the (biphenylyloxy)acetate (III). Heating of ester (III) with m-fluorobenzylamine (IV) at 85 C produced amide (V), which was subsequently reduced to amine (VI) by means of borane, generated in situ from NaBH4 and BF3. Finally, condensation of the secondary amine (VI) with methyl isocyanate gave rise to the title urea derivative.
| 【1】 Fex, T.; Asp, B.; Stamvik, A.; Carlsson, J.-I.; Billstrom, A. (Pharmacia AB); Novel antitumour cpds. with antimitotic activity. WO 9529155 . |
| 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) | 55986 | 4,4'-Biphenol; 4,4'-Dihydroxybiphenyl; 4,4'-Dihydroxydiphenyl; 4,4'-Diphenol | 92-88-6 | C12H10O2 | 详情 | 详情 |
| (II) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (III) | 55987 | ethyl 2-[(4'-hydroxy[1,1'-biphenyl]-4-yl)oxy]acetate | C16H16O4 | 详情 | 详情 | |
| (IV) | 48834 | 3-Fluorobenzylamine | 100-82-3 | C7H8FN | 详情 | 详情 |
| (V) | 55990 | N-(3-fluorobenzyl)-2-[(4'-hydroxy[1,1'-biphenyl]-4-yl)oxy]acetamide | C21H18FNO3 | 详情 | 详情 | |
| (VI) | 55991 | 4'-{2-[(3-fluorobenzyl)amino]ethoxy}[1,1'-biphenyl]-4-ol | C21H20FNO2 | 详情 | 详情 |
Extended Information