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【结 构 式】 
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【药物名称】(-)-cis-MR-22, (-)-MR-22 【化学名称】(-)-cis-2-[N-(1-Adamantyl)-N-methylaminomethyl]-1-phenylcyclopropanecarboxylic acid methyl ester 【CA登记号】290342-29-9 【 分 子 式 】C23H31NO2 【 分 子 量 】353.50902 |
【开发单位】Università degli Studi di Catania (Originator), Università degli Studi di Messina (Originator) 【药理作用】Antiglaucoma Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, sigma Receptor Agonists |
合成路线1
Opening of the known lactone (I) with HBr in HOAc produces the racemic cis bromo-acid (II). Acid (II) is then converted to the corresponding methyl ester (III) by chlorination with SOCl2, followed by treatment with methanolic HCl. Acylation of 1-adamantanamine (IV) with ethyl formate yields the formamide (V), which is subsequently reduced to the N-methyl amine (VI) employing LiAlH4 in THF. Finally, alkylation of the secondary amine (VI) with bromo ester (III) in the presence of NaHCO3 in hot DMF gives rise to the title compound.
| 【1】 Ronsisvalle, G.; et al.; Substituted 1-phenyl-2-cyclopropylmethylamines with high affinity and selectively for sigma sites. Bioorg Med Chem 2000, 8, 6, 1503. |
| 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) | 28144 | 1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one | C11H10O2 | 详情 | 详情 | |
| (II) | 59006 | (1S,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid | C11H11BrO2 | 详情 | 详情 | |
| (III) | 59007 | methyl (1S,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylate | C12H13BrO2 | 详情 | 详情 | |
| (IV) | 53978 | 1-Adamantanamine; 1-Adamantylamine; 1-Aminoadamantane | 768-94-5 | C10H17N | 详情 | 详情 |
| (V) | 59008 | 1-adamantylformamide | C11H17NO | 详情 | 详情 | |
| (VI) | 59009 | N-(1-adamantyl)-N-methylamine; N-methyl-1-adamantanamine | C11H19N | 详情 | 详情 |
合成路线2
In a closely related method, bromo-ester (I) is condensed with 1-adamantanamine (II) in hot DMF to afford amino ester (III). The secondary amine of (III) is then alkylated with iodomethane to produce the title compound.
| 【1】 Marrazzo, A.; et al.; Synthesis of (+)- and (-)-cis-2-[(1-adamantylamino)-methyl]-1-phenylcyclopropane derivatives as high affinity probes for sigma1 and sigma2 binding sites. Farmaco 2002, 57, 1, 45. |
| 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) | 59007 | methyl (1S,2R)-2-(bromomethyl)-1-phenylcyclopropanecarboxylate | C12H13BrO2 | 详情 | 详情 | |
| (II) | 53978 | 1-Adamantanamine; 1-Adamantylamine; 1-Aminoadamantane | 768-94-5 | C10H17N | 详情 | 详情 |
| (III) | 59010 | methyl (1S,2R)-2-[(1-adamantylamino)methyl]-1-phenylcyclopropanecarboxylate | C22H29NO2 | 详情 | 详情 |