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【结 构 式】 
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【药物名称】Asimadoline, EMR-63320, EMD-61753 【化学名称】N-Methyl-N-[1(S)-phenyl-2-[3(S)-hydroxypyrrolidin-1-yl]]ethyl-2,2-diphenylacetamide 【CA登记号】153205-46-0 【 分 子 式 】C27H30N2O2 【 分 子 量 】414.55235 |
【开发单位】Merck KGaA (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, GASTROINTESTINAL DRUGS, Irritable Bowel Syndrome, Agents for, Opioid Analgesics, kappa-Opioid Agonists |
合成路线1
The condensation of (S)-phenylglycine (I) with ethyl chloroformate gave carbamate (II). After activation of (II) as the mixed anhydride with ethyl chloroformate in the presence of N-methylmorpholine, coupling with (S)-3-hydroxypyrrolidine (III) provided amide (IV). Reduction of both amide and carbamate groups of (IV) employing LiAlH4 in refluxing THF yielded diamine (V). This was finally condensed with diphenylacetyl chloride (VI) to furnish the title amide The condensation of (S)-phenylglycine (I) with ethyl chloroformate gave carbamate (II). After activation of (II) as the mixed anhydride with ethyl chloroformate in the presence of N-methylmorpholine, coupling with (S)-3-hydroxypyrrolidine (III) provided amide (IV). Reduction of both amide and carbamate groups of (IV) employing LiAlH4 in refluxing THF yielded diamine (V). This was finally condensed with diphenylacetyl chloride (VI) to furnish the title amide.
| 【1】 Ackermann, K.-A.; Budak, J.; Bathe, A.; Gottschlich, R.; Helfert, B.; Stein, I. (Merck Patent GmbH); Method for producing enantiomer-free N-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidine-1-yl)ethyl]-2,2-diphenyl acetamide. DE 19827633; WO 9954298 . |
| 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) | 10716 | (2S)-2-Amino-2-phenylethanoic acid; L-(+)-alpha-Phenylglycine | 2935-35-5 | C8H9NO2 | 详情 | 详情 |
| (II) | 12171 | (2S)-2-[(Ethoxycarbonyl)amino]-2-phenylethanoic acid | C11H13NO4 | 详情 | 详情 | |
| (III) | 14490 | (3R)tetrahydro-1H-pyrrol-3-ol; R-3-hydroxypyrrolidine | 2799-21-5 | C4H9NO | 详情 | 详情 |
| (IV) | 31452 | ethyl (1S)-2-[(3S)-3-hydroxypyrrolidinyl]-2-oxo-1-phenylethylcarbamate | C15H20N2O4 | 详情 | 详情 | |
| (V) | 31453 | (3S)-1-[(2S)-2-(methylamino)-2-phenylethyl]-3-pyrrolidinol | C13H20N2O | 详情 | 详情 | |
| (VI) | 23800 | Diphenylacetyl chloride; 2,2-diphenylacetyl chloride | 1871-76-7 | C14H11ClO | 详情 | 详情 |