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【结 构 式】 
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【药物名称】ICI-197067 【化学名称】(-)-2-(3,4-Dichlorophenyl)-N-methyl-N-[2-methyl-1(S)-(pyrrolidin-1-ylmethyl)propyl]acetamide hydrochloride 【CA登记号】115199-69-4, 136328-64-8 (free base) 【 分 子 式 】C18H27Cl3N2O 【 分 子 量 】393.78769 |
【开发单位】AstraZeneca (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, kappa-Opioid Agonists |
合成路线1
N-tert-Butoxycarbonyl valine (I) was converted to amide (III) by coupling with pyrrolidine (II) by means of DCC and HOBT. Simultaneous reduction of both carbamoyl and amide functions of (III) using excess LiAlH4 in THF gave the chiral diamine (IV). Final acylation of (IV) with (3,4-dichlorophenyl)acetyl chloride (V) in CH2Cl2 yielded the target amide.
| 【1】 Costello, G.F.; et al.; 2-(3, 4-Dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl)-1-substituted-ethyl]-acetamides: The use of conformational analysis in the development of a novel series of potent opioid kappa agonists. J Med Chem 1991, 34, 1, 181-9. |
| 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) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (II) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (III) | 26112 | tert-butyl (1S)-2-methyl-1-(1-pyrrolidinylcarbonyl)propylcarbamate | C14H26N2O3 | 详情 | 详情 | |
| (IV) | 26113 | N-methyl-N-[(1S)-2-methyl-1-(1-pyrrolidinylmethyl)propyl]amine; (2S)-N,3-dimethyl-1-(1-pyrrolidinyl)-2-butanamine | C10H22N2 | 详情 | 详情 | |
| (V) | 26111 | 2-(3,4-dichlorophenyl)acetyl chloride | C8H5Cl3O | 详情 | 详情 |
Extended Information