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【结 构 式】 
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【药物名称】RP-67580 【化学名称】(+)-(3aR,7aR)-2-[1-Imino-2-(2-methoxyphenyl)ethyl]-7,7-diphenylperhydroisoindol-4-one 【CA登记号】135911-02-3 【 分 子 式 】C29H30N2O2 【 分 子 量 】438.57465 |
【开发单位】Aventis Pharma (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Tachykinin NK1 Antagonists |
合成路线1
The cyclization of 4,4-diphenyl-2-cyclohexen-1-one (I) with N-benzyl-N-(butoxymethyl)-N-(trimethylsilylmethyl)amine (II) gives 2-benzyl-7,7-diphenylperhydroisoindol-4-one (III), which is debenzylated by hydrogenation with H2 over Pd/C to afford 7,7-diphenylperhydroisoindol-4-one (IV). The optical resolution of (IV) yields the desired enantiomer, which is finally condensed with 2-(2-methoxyphenyl)acetimidic acid ethyl ester tetrafluoroborate (V).
| 【1】 Peyronel, J.-F.; et al.; Synthesis of RP-67,580, a new potent nonpeptide substance P antagonist. Bioorg Med Chem Lett 1992, 2, 1, 37. |
| 【2】 Lowe, J.A. III; Substance P antagonists. Drugs Fut 1992, 17, 12, 1115. |
| 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) | 30325 | 4,4-diphenyl-2-cyclohexen-1-one | C18H16O | 详情 | 详情 | |
| (II) | 19702 | N-benzyl-N-(butoxymethyl)-N-[(trimethylsilyl)methyl]amine; N-(butoxymethyl)(phenyl)-N-[(trimethylsilyl)methyl]methanamine | C16H29NOSi | 详情 | 详情 | |
| (III) | 42930 | (3aR,7aR)-2-benzyl-7,7-diphenyloctahydro-4H-isoindol-4-one | C27H27NO | 详情 | 详情 | |
| (IV) | 42931 | (3aR,7aR)-7,7-diphenyloctahydro-4H-isoindol-4-one | C20H21NO | 详情 | 详情 | |
| (V) | 42932 | ethyl 2-(2-methoxyphenyl)ethanimidoate | C11H15NO2 | 详情 | 详情 |