【结 构 式】 |
【药物名称】Nefazodone hydrochloride, MJ-13754-1, BMY-13754-1, Rulivan, Reseril, Menfazona, Nefadar, Dutonin, Serzone 【化学名称】2-[3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl]-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one hydrochloride 【CA登记号】82752-99-6, 83366-66-9 (free base) 【 分 子 式 】C25H33Cl2N5O2 【 分 子 量 】506.48006 |
【开发单位】Bristol-Myers Squibb (Originator), Cephalon (Licensee), Lipha (Licensee), Menarini (Licensee), Mitsubishi Pharma (Licensee) 【药理作用】Antidepressants, Diabetic Neuropathy, Agents for, ENDOCRINE DRUGS, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Diabetic Complications, 5-HT Reuptake Inhibitors, 5-HT2A Antagonists |
合成路线1
Reaction of 2-ethyloxazoline (A) with phenol (B) affords the propionamide (I). Treatment of (I) with phosgene yields the imino chloride (II), which is reacted with methylcarbazate to provide the amidrazone (III). Cyclodehydration of (III) gives the triazolone (IV). Alkylation of (IV) with 1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine affords nefazodone, which is isolated as the hydrochloride salt.
【1】 Fathi, N.H.; et al.; J Heterocycl Chem 1985, 22, 10, 1121. |
【2】 Eison, M.S.; Smith, D.W.; Madding, G.D.; Taylor, D.P.; Nefazodone Hydochloride. Drugs Fut 1987, 12, 8, 758. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(B) | 23540 | Phenol | 108-95-2 | C6H6O | 详情 | 详情 |
(A) | 28216 | 2-ethyl-4,5-dihydro-1,3-oxazole | 10431-98-8 | C5H9NO | 详情 | 详情 |
(I) | 28217 | N-(2-phenoxyethyl)propanamide | C11H15NO2 | 详情 | 详情 | |
(II) | 28218 | N-(2-phenoxyethyl)propanimidoyl chloride | C11H14ClNO | 详情 | 详情 | |
(III) | 28219 | methyl 2-[(Z)-1-[(2-phenoxyethyl)amino]propylidene]-1-hydrazinecarboxylate | C13H19N3O3 | 详情 | 详情 | |
(IV) | 28220 | 5-ethyl-4-(2-phenoxyethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one | C12H15N3O2 | 详情 | 详情 | |
(V) | 28221 | 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine | 39577-43-0 | C13H18Cl2N2 | 详情 | 详情 |
(C) | 12556 | methyl 1-hydrazinecarboxylate; methyl carbazate | 6294-89-9 | C2H6N2O2 | 详情 | 详情 |