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【结 构 式】 
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【药物名称】HSP-117 【化学名称】(2S,3S)-3-(5-Isopropyl-2,3-dihydrobenzofuran-7-ylmethylamino)-2-phenylpiperidine dihydrochloride 【CA登记号】 【 分 子 式 】C23H32Cl2N2O 【 分 子 量 】423.43029 |
【开发单位】Hisamitsu (Originator) 【药理作用】Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS, Tachykinin NK1 Antagonists |
合成路线1
Reductive condensation of 3-amino-2-chloropyridine (I) with 5-isopropylbenzofuran-7-carbaldehyde (II) in the presence of sodium triacetoxyborohydride provided secondary amine (III). Displacement of the chlorine atom of (III) with phenylmagnesium bromide (IV) using NiCl2 produced phenylpyridine (V), which was hydrogenated with hydrogen over PtO2 in acetic acid to give racemic piperidine (VI). Resolution of (VI) with (R)-(-)-mandelic acid yielded the (2S,3S)-isomer, which was finally isolated as the dihydrochloride salt.
| 【1】 Tanaoue, Y.; Beppu, K.; Okayama, A.; Sakamoto, O. (Hisamitsu Pharmaceutical Co., Ltd.); Piperidine derivs.. EP 0826684; US 5886011; WO 9630367 . |
| 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) | 11160 | 2-Chloro-3-pyridinamine; 2-Chloro-3-pyridinylamine; 3-Amino-2-chloropyridine; 2-Chloro-3-aminopyridine | 6298-19-7 | C5H5ClN2 | 详情 | 详情 |
| (II) | 26501 | 5-isopropyl-2,3-dihydro-1-benzofuran-7-carbaldehyde | C12H14O2 | 详情 | 详情 | |
| (III) | 26502 | 2-chloro-N-[(5-isopropyl-2,3-dihydro-1-benzofuran-7-yl)methyl]-3-pyridinamine | C17H19ClN2O | 详情 | 详情 | |
| (IV) | 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 |
| (V) | 26503 | N-[(5-isopropyl-2,3-dihydro-1-benzofuran-7-yl)methyl]-2-phenyl-3-pyridinamine | C23H24N2O | 详情 | 详情 | |
| (VI) | 26504 | N-[(5-isopropyl-2,3-dihydro-1-benzofuran-7-yl)methyl]-2-phenyl-3-piperidinamine | C23H30N2O | 详情 | 详情 |