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【结 构 式】 
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【分子编号】68619 【品名】N-methoxy-N,1-dimethylpiperidine-4-carboxamide 【CA登记号】 |
【 分 子 式 】C9H18N2O2 【 分 子 量 】186.254 【元素组成】C 58.04% H 9.74% N 15.04% O 17.18% |
合成路线1
该中间体在本合成路线中的序号：(II)Metalation of 2-chloropyridine (I) with BuLi in the presence of N,Ndimethylethanolamine in hexane at –78 °C, followed by condensation with N-methoxy-N,1-dimethylpiperidine-4-carboxamide (II) in hexane provides (6-chloropyridin-2-yl)(1-methylpiperidin-4-yl)methanone (III). Condensation of chloropyrimidine derivative (III) with benzophenone imine, Pd2dba3, BINAP and t-BuONa in refluxing toluene yields compound (IV), which by hydrolysis with HCl in THF furnishes (6-aminopyridin-2-yl)(1-methylpiperidin-4-yl)methanone (V). N-Acylation of amine (V) with 2,4,6-trifluorobenzoyl chloride (VI), optionally in the presence of Et3N in THF or refluxing 1,4-dioxane, generates lasmiditan (VII), which is finally treated with NH4Cl in MeOH or HCl in refluxing i-PrOH .
| 【1】 Kohlman, D.T., Mancuso, V., Cohen, M.P. et al. (Eli Lilly and Company). Pyridinoylpiperidines as 5-HT1F agonists. EP 1492786, JP 2005530722, JP 2010159272, US 2005222206, US 7423050, US 8044207, WO 2003084949. |
| 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) | 17503 | 2-chloropyridine | 109-09-1 | C5H4ClN | 详情 | 详情 |
| (II) | 68619 | N-methoxy-N,1-dimethylpiperidine-4-carboxamide | C9H18N2O2 | 详情 | 详情 | |
| (III) | 68620 | (6-chloropyridin-2-yl)(1-methylpiperidin-4-yl)methanone | C12H15ClN2O | 详情 | 详情 | |
| (IV) | 68621 | (6-((diphenylmethylene)amino)pyridin-2-yl)(1-methylpiperidin-4-yl)methanone | C25H25N3O | 详情 | 详情 | |
| (V) | 68622 | (6-aminopyridin-2-yl)(1-methylpiperidin-4-yl)methanone | C12H17N3O | 详情 | 详情 | |
| (VI) | 68623 | 2,4,6-trifluorobenzoyl chloride | 79538-29-7 | C7H2ClF3O | 详情 | 详情 |
| (VII) | 68624 | 2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl)benzamide | C19H18F3N3O2 | 详情 | 详情 |