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【结 构 式】 
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【药物名称】BIA-2-059 【化学名称】Acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10(R)-yl ester 【CA登记号】186694-45-1, 186694-11-1 (undefined isomer) 【 分 子 式 】C17H16N2O3 【 分 子 量 】296.32867 |
【开发单位】Bial (Originator) 【药理作用】Antiepileptic Drugs, NEUROLOGIC DRUGS, Sodium Channel Blockers |
合成路线1
Oxcarbazepine (I) was reduced with NaBH4 to afford the racemic alcohol (IIa-b). Esterification with (-)-menthoxyacetic acid chloride (III) in the presence of dimethylaminopyridine provided the diastereomeric mixture of esters (IV) and (V), from which the desired isomer (V) was isolated by fractional crystallization from CH2Cl2/EtOAc. Basic hydrolysis of (V) then provided pure (R)-alcohol (VI). Finally, esterification of (VI) with acetyl chloride led to the title acetate ester.
| 【1】 Garrett, J.; Soares-da-Silva, P.; Freitas, A.P.; Cunha, R.A.; Benes, J.; Parada, A.; Learmonth, D.A.; Alves, P.C.; Figueiredo, A.; Anticonvulsant and sodium channel-blocking properties of novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives. J Med Chem 1999, 42, 14, 2582. |
| 【2】 Benes, J.; Vieira Araujo Soares da Silva, P.M. (Portela & Ca., SA); Substd. dihydrodibenzo[b,f]azepines, method of their preparation, their use in the treatment of some central nervous system disorders, and pharmaceutical compsns. containing them. EP 0751129; US 5753646 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIa) | 33775 | (10S)-10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide | C15H14N2O2 | 详情 | 详情 | |
| (IIb),(VI) | 33779 | (10R)-10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide | C15H14N2O2 | 详情 | 详情 | |
| (I) | 33774 | 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide | 28721-07-5 | C15H12N2O2 | 详情 | 详情 |
| (III) | 33776 | 2-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]acetyl chloride | 15356-62-4 | C12H21ClO2 | 详情 | 详情 |
| (IV) | 33777 | (10S)-5-(aminocarbonyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl 2-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]acetate | C27H34N2O4 | 详情 | 详情 | |
| (V) | 33778 | (10R)-5-(aminocarbonyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl 2-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy]acetate | C27H34N2O4 | 详情 | 详情 |