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【结 构 式】 
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【药物名称】Ricainide, Indecainide, LY-135837, Decabid 【化学名称】9-[3-[(1-Methylethyl)amino]propyl]-9H-fluorene-9-carboxamide 【CA登记号】74517-78-5, 73681-12-6 (monoHCl) 【 分 子 式 】C20H24N2O 【 分 子 量 】308.42708 |
【开发单位】Lilly (Originator) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS |
合成路线1
The condensation of 9-cyanofluorene (I) with 3-(dimethylamino)propyl chloride (II) by means of sodium amide in refluxing THF gives 9-[3-(dimethyl amino)propyl]-9-cyanofluorene (III), which is hydrolyzed partially with hot sulfuric acid water.
| 【1】 Wiegand, H.; Bosslet, S.; Bosslet, K.; Sedlacek, K. (Behringwerke AG); Neoglucoproteins, their preparation and use. AU 8944368; EP 0368131 . |
| 【2】 Lacefield, W.B.; Simon R.L. (Eli Lilly and Company); Antiarrhythmic method. US 4197313 . |
| 【3】 Serradell, M.N.; Sneddon, J.; Castaner, J.; Indecainide. Drugs Fut 1985, 10, 2, 121. |
合成路线2
The condensation of fluorene-9-carboxamide (IV) with acrylonitrile (V) by means of benzyltrimethylammonium hydroxide (VI) in hot dioxane gives 9-carbamoyl-9-(2-cyanoethyl)fluorene (VII), which is then hydrogenated and condensed with isopropylamine (VIII) and H2 over PtO2 with the same isopropylamine (VIII) as solvent.
| 【1】 Lavagnino, E.R.; Pike, A.J.; Campbell, J.B. (Eli Lilly and Company); 9-Carbamoyl-9-(2-cyanoethyl)fluorenes. DD 158395; EP 0038676; GB 2074161; JP 1125363; US 4282170 . |
| 【2】 Serradell, M.N.; Sneddon, J.; Castaner, J.; Indecainide. Drugs Fut 1985, 10, 2, 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 28969 | 9H-fluorene-9-carboxamide | C14H11NO | 详情 | 详情 | |
| (V) | 28970 | 3-butenenitrile | 109-75-1 | C4H5N | 详情 | 详情 |
| (VI) | 27394 | Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide | 100-85-6 | C10H17NO | 详情 | 详情 |
| (VII) | 28971 | 9-(2-cyanoethyl)-9H-fluorene-9-carboxamide | C17H14N2O | 详情 | 详情 | |
| (VIII) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |