|
【结 构 式】 
|
【药物名称】Doxefazepam, SAS-643, Doxans 【化学名称】7-Chloro-5-(o-fluorophenyl)-1,3-dihydro-3-hydroxy-1-(2-hydroxyethyl)-2H-1,4-benzodiazepin-2-one 【CA登记号】40762-15-0 【 分 子 式 】C17H14ClFN2O3 【 分 子 量 】348.76413 |
【开发单位】Schiapparelli Farmaceutici (Originator) 【药理作用】PSYCHOPHARMACOLOGIC DRUGS, Sedative/Hypnotics, Sleep Disorders, Treatment of, Benzodiazepines, GABA(A) BZ Site Receptor Agonists |
合成路线1
Compound can be prepared in two similar ways both starting from 7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one-4-oxide (I): 1) The condensation of (I) with 2-bromoethanol (A) by means of NaH in DMF gives the N-hydroxyethyl derivative (II), which by refluxing with acetic anhydride is converted into 7-chloro-1,3-dihydro-1-(2-acetoxyethyl)-3-acetoxy-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one (III). Finally, (III) is deacetylated with methanolic ammonia. 2) The condensation of (I) with 2-bromoethylacetate (B) as before gives the N-acetoxyethyl derivative (IV), which by refluxing with acetic anhydride is converted into (III).
| 【1】 Tamagnone, G.F.; et al.; A new benzodiazepine: 1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepine-2-one. J Pharm Pharmacol 1974, 26, 566. |
| 【2】 De Marchi, F.; Tamagnone, G.F.; Benzodiazepine compounds for therapeutical use. DE 2338058; ES 405260; FR 2194432; GB 1431282; JP 49080086 . |
| 【3】 Tamagnone, G.F.; et al.; A new series of benzodiazepines: 1-Hydroxyalkyl derivatives of 1,3-dihydro-2H-1,4-benzodiazepin-2-one. Arzneim-Forsch Drug Res 1975, 25, 5, 720-722. |
| 【4】 de Angelis, L.; Castaner, J.; SAS-643. Drugs Fut 1978, 3, 2, 145. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (B) | 33463 | 2-bromoethyl acetate | 927-68-4 | C4H7BrO2 | 详情 | 详情 |
| (I) | 33459 | 7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-4-ium-4-olate | C15H10ClFN2O2 | 详情 | 详情 | |
| (II) | 33460 | 7-chloro-5-(2-fluorophenyl)-1-(2-hydroxyethyl)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-4-ium-4-olate | C17H14ClFN2O3 | 详情 | 详情 | |
| (III) | 33461 | 2-[3-(acetoxy)-7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-1-yl]ethyl acetate | C21H18ClFN2O5 | 详情 | 详情 | |
| (IV) | 33462 | 1-[2-(acetoxy)ethyl]-7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-4-ium-4-olate | C19H16ClFN2O4 | 详情 | 详情 |