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【结 构 式】 
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【药物名称】LY-349950 【化学名称】N-[3-[2-(Dimethylamino)ethyl]-2-methyl-1H-indol-5-yl]-4-fluorobenzamide hydrochloride 【CA登记号】189805-93-4, 189806-34-6 (free base) 【 分 子 式 】C20H23ClFN3O 【 分 子 量 】375.87721 |
【开发单位】Lilly (Originator), Synaptic (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Antimigraine Drugs, 5-HT1F Agonists |
合成路线1
Acylation of 4-nitroaniline (I) with 4-fluorobenzoyl chloride (II) affords benzanilide (III). Catalytic hydrogenation of the nitro group of (III) employing Pt/C then gives amine (IV). Diazotization of (IV), followed by reduction with SnCl2 leads to hydrazine (V). Reaction of 5-chloro-2-pentanone (VI) with dimethylamine yields the amino ketone (VII). Finally, the title compound is obtained by Fisher indole synthesis from aryl hydrazine (V) and ketone (VII) under acidic conditions.
| 【1】 Xu, Y.-C.; Johnson, K.W.; Phebus, L.A.; et al.; N-[3-(2-Dimethylaminoethyl)-2-methyl-1-H-indol-5-yl]-4-fluorobenzamide: A potent, selective, and orally active 5-HT1F receptor agonist potentially useful for migraine therapy. J Med Chem 2001, 44, 24, 4031. |
| 【2】 Johnson, K.W.; Phebus, L.A. (Eli Lilly and Company); Use of a serotonin 5-HT1F agonist in the manufacture of a medicament for treating or ameliorating the symptoms of common cold or allergic rhinitis. EP 0824917; US 5962473; WO 9806402 . |
| 【3】 Fritz, J.E.; Hahn, P.J.; Kaldor, S.W.; Siegel, M.G.; Xu, Y.-C. (Eli Lilly and Company); N-[2-Substd.-3-(2-aminoethyl)-1H-indol-5-yl]-amides: New 5-HT1F agonists. EP 0768301; JP 1999513666; WO 9713512 . |
| 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) | 15547 | 4-nitrophenylamine; p-Nitroaniline; 4-nitroaniline | 100-01-6 | C6H6N2O2 | 详情 | 详情 |
| (II) | 17263 | 4-fluorobenzoyl chloride | 403-43-0 | C7H4ClFO | 详情 | 详情 |
| (III) | 60456 | 4-fluoro-N-(4-nitrophenyl)benzamide | C13H9FN2O3 | 详情 | 详情 | |
| (IV) | 60457 | N-(4-aminophenyl)-4-fluorobenzamide | C13H11FN2O | 详情 | 详情 | |
| (V) | 60458 | 4-fluoro-N-(4-hydrazinophenyl)benzamide | C13H12FN3O | 详情 | 详情 | |
| (VI) | 60460 | 5-chloro-2-pentanone | C5H9ClO | 详情 | 详情 | |
| (VII) | 60459 | 5-(dimethylamino)-2-pentanone | C7H15NO | 详情 | 详情 |