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【结 构 式】 
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【药物名称】ORG-25435 【化学名称】2(R)-[N,N-Bis(2-methoxyethyl)amino]butyric acid 4-methyl-2,6-dimethoxyphenyl ester hydrobromide 【CA登记号】256456-73-2 ((R)-isomer, free base), 256456-45-8 (free base) 【 分 子 式 】C19H32BrNO6 【 分 子 量 】450.37399 |
【开发单位】Organon (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Anesthetic Drugs, GABA(A) Receptor Modulators |
合成路线1
Treatment of 2,6-dimethoxy-4-methylphenol (I) with 2-bromobutyryl bromide (II) and Et3N in dichloromethane provides 2,6-dimethoxy-4-methylphenyl ester (III), which is converted into the target product by reaction with bis(2-methoxyethyl)amine (IV) and Et3N in refluxing toluene. The target (R)-enantiomer is isolated by resolution of the racemic amino ester by either enantiospecific enzyme hydrolysis of the corresponding (S)-isomer or by means of chiral HPLC.
| 【1】 Bennett, D.J.; Belelli, D.; Anderson, A.; et al.; alpha-Amino acid phenolic ester derivatives: Novel water-soluble general anesthetic agents which allosterically modulate GABAA receptors. J Med Chem 2001, 44, 22, 3582. |
| 【2】 Hamilton, N.M. (Akzo Nobel N.V.); alpha-Amino acid phenyl ester derivs.. EP 1098871; WO 0005196 . |
| 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) | 47212 | 2,6-dimethoxy-4-methylphenol | C9H12O3 | 详情 | 详情 | |
| (II) | 47213 | 2-bromobutanoyl bromide | 26074-52-2 | C4H6Br2O | 详情 | 详情 |
| (III) | 47214 | 2,6-dimethoxy-4-methylphenyl 2-bromobutanoate | C13H17BrO4 | 详情 | 详情 | |
| (IV) | 23785 | N,N-bis(2-methoxyethyl)amine; 2-methoxy-N-(2-methoxyethyl)-1-ethanamine | 111-95-5 | C6H15NO2 | 详情 | 详情 |
| (V) | 56452 | 2,6-dimethoxy-4-methylphenyl 2-[bis(2-methoxyethyl)amino]butanoate | C19H31NO6 | 详情 | 详情 |