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【结 构 式】 
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【药物名称】S-34324 【化学名称】4-(5-Fluoroindan-2-ylmethyl)-4,5-dihydro-1H-imidazole 【CA登记号】276235-47-3 【 分 子 式 】C13H15FN2 【 分 子 量 】218.2763 |
【开发单位】Servier (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, alpha2-Adrenoceptor Antagonists, Norepinephrine Transporter (NET) Inhibitors, Serotonine Transporter (SERT) Inhibitors |
合成路线1
2-(Hydroxymethyl)-5-fluoroindane (I) was converted to bromide (II) upon treatment with CBr4 and PPh3. Alkylation of N-(diphenylmethylene)aminoacetonitrile (III) with bromide (II) under phase-transfer conditions furnished amino nitrile (V), which was reduced to diamine (VI) by using LiAlH4 in THF. Finally, condensation of diamine (V) with formamidine acetate yielded the target imidazoline.
| 【1】 Newman-Tancredi, A.; Lacoste, J.-M.; Millan, M.; Cordi, A.; Gobert, A. (ADIR et Cie.); Imidazoline derivs., preparation and pharmaceutical compsns. containing them. EP 1010693; FR 2787451; JP 2000178255; US 6127396 . |
| 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) | 46414 | (5-fluoro-2,3-dihydro-1H-inden-2-yl)methanol | C10H11FO | 详情 | 详情 | |
| (II) | 46415 | 2-(bromomethyl)-5-fluoroindane | C10H10BrF | 详情 | 详情 | |
| (III) | 46416 | 2-[(dibenzylene)amino]acetonitrile | 70591-20-7 | C15H12N2 | 详情 | 详情 |
| (IV) | 46417 | 2-amino-3-(5-fluoro-2,3-dihydro-1H-inden-2-yl)propanenitrile | C12H13FN2 | 详情 | 详情 | |
| (V) | 46418 | 3-(5-fluoro-2,3-dihydro-1H-inden-2-yl)-1,2-propanediamine; 2-amino-1-[(5-fluoro-2,3-dihydro-1H-inden-2-yl)methyl]ethylamine | C12H17FN2 | 详情 | 详情 |
合成路线2
In an alternative procedure, Wadsworth-Emmons condensation of 5-fluoroindan-2-one (VI) with triethyl phosphonoacetate gave the indeneacetate (VII), which was reduced to aldehyde (VIII) employing diisobutylaluminum hydride. Strecker reaction of aldehyde (VIII) with NaCN and NH-4-Cl produced amino nitrile (IX). This was reduced to diamine (X) using LiAlH4, and then condensed with formamidine acetate to produce imidazoline (XI). Finally, catalytic hydrogenation of indene (XI) over Pd/C provided the title indane derivative.
| 【1】 Persigand, T.; Lacoste, J.-M.; Audinot, V.; Millan, M.J.; Newman-Tancredi, A.; Cordi, A.A.; Berque-Bestel, I.; Potential antidepressants displayed combined alpha2-adrenoceptor antagonist and monoamine uptake inhibitor properties. J Med Chem 2001, 44, 5, 787. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 46419 | 5-fluoro-1,3-dihydro-2H-inden-2-one | C9H7FO | 详情 | 详情 | |
| (VII) | 46420 | ethyl 2-(5-fluoro-1H-inden-2-yl)acetate | C13H13FO2 | 详情 | 详情 | |
| (VIII) | 46421 | 2-(5-fluoro-1H-inden-2-yl)acetaldehyde | C11H9FO | 详情 | 详情 | |
| (IX) | 46422 | 2-amino-3-(5-fluoro-1H-inden-2-yl)propanenitrile | C12H11FN2 | 详情 | 详情 | |
| (X) | 46423 | 3-(5-fluoro-1H-inden-2-yl)-1,2-propanediamine; 2-amino-1-[(5-fluoro-1H-inden-2-yl)methyl]ethylamine | C12H15FN2 | 详情 | 详情 | |
| (XI) | 46424 | 4-[(5-fluoro-1H-inden-2-yl)methyl]-4,5-dihydro-1H-imidazole | C13H13FN2 | 详情 | 详情 |