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【结 构 式】 
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【药物名称】Fluoxetine hydrochloride, LY-110140, Fluoxeren, Framex, Adofen, Sarafem, Flunirin, Lovan, Fluctin, Prozac 【化学名称】(±)-N-Methyl-gamma-[4-(trifluoromethyl)phenoxy]benzenepropanamine hydrochloride 【CA登记号】59333-67-4, 54910-89-3 (free base) 【 分 子 式 】C17H19ClF3NO 【 分 子 量 】345.79528 |
【开发单位】Indevus (Proprietary), Lilly (Originator), Menarini (Not Determined), Galen (Marketer), Chugai (Licensee), Ferrer (Licensee), Gedeon Richter (Licensee), Biovail (Formulation) 【药理作用】Antidepressants, Antiobesity Drugs, Anxiolytics, METABOLIC DRUGS, Mood Disorders, Treatment of, Obsessive-Compulsive Disorder (OCD), Treatment of, Posttraumatic Stress Disorder (PTSD), Treatment of, Premenstrual Syndrome, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Bulimia, Treatment of Eating Disorders, Treatment of Nutritional Disorders, 5-HT Reuptake Inhibitors |
合成路线1
The reduction of beta-dimethylaminopropiophenone (I) with diborane in THF gives N,N-dimethyl-3-phenyl-3-hydroxypropylamine (II), which is converted into N,N-dimethyl-3-phenyl-3-chloropropylamine (III) wtih refluxing SOCl2. The condensation of 4-trifluoromethylphenol (A) with (III) by means of NaOH in refluxing methanol affords N,N-dimethyl-3-phenyl-3-(p-trifluoromethylphenoxy) propylamine (IV), which is treated with BrCN in benzene to yield N-methyl-N-cyano-3-phenyl-3-(p-trifluoromethylphenoxy)propylamine (V). Finally, (V) is hydrolyzed with KOH in ethylene glycol at 130 C.
| 【1】 Molloy, B.B.; Schmiegel, K.K. (Eli Lilly and Company); Arloxyphenylpropylamines. DE 2500110; ES 433720; FR 2257288; GB 1493961; JP 50101333; US 4314081 . |
| 【2】 Paton, D.M.; Castaner, J.; Fluoxetine. Drugs Fut 1977, 2, 1, 27. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 33607 | 4-(trifluoromethyl)phenol | 402-45-9 | C7H5F3O | 详情 | 详情 |
| (I) | 33602 | 3-(Dimethylamino)propiophenone; beta-Dimethylaminopropiophenone; 3-(dimethylamino)-1-phenyl-1-propanone | 879-72-1 | C11H15NO | 详情 | 详情 |
| (II) | 33603 | 3-(dimethylamino)-1-phenyl-1-propanol | C11H17NO | 详情 | 详情 | |
| (III) | 33604 | N-(3-chloro-3-phenylpropyl)-N,N-dimethylamine; 3-chloro-N,N-dimethyl-3-phenyl-1-propanamine | C11H16ClN | 详情 | 详情 | |
| (IV) | 33605 | N,N-dimethyl-N-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]amine; N,N-dimethyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine | C18H20F3NO | 详情 | 详情 | |
| (V) | 33606 | methyl[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]cyanamide | C18H17F3N2O | 详情 | 详情 |