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【结 构 式】 
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【分子编号】11436 【品名】4-[Benzyl(isopropyl)amino]-2-(2-chlorophenyl)-2-(2-piperidinoethyl)butanenitrile 【CA登记号】 |
【 分 子 式 】C27H36ClN3 【 分 子 量 】438.05576 【元素组成】C 74.03% H 8.28% Cl 8.09% N 9.59% |
合成路线1
该中间体在本合成路线中的序号：(III)The alkylation of the alpha-N-piperidinylethyl derivative of the 2-chlorophenylacetonitrile (I) with N-benzyl-N-isopropylaminoethyl chloride (II) (4) and sodium amide in refluxing toluene gives (rac)-alpha-(2-chlorophenyl)-alpha-[2-[(1-methylethyl)(phenylmethyl) amino]ethyl]-1-piperidinebutanenitrile (III). Hydration of the nitrile (III) with sulfuric acid provided (rac)-alpha-[1-[(1-methylethyl)(phenylmethyl)amino]ethyl]-1-piperidinebutanamide (IV), and subsequent catalytic hydrogenolysis of the N-benzyl group yielded (rac)-alpha-(2-chlorophenyl)-alpha-[(1-methylethyl)amino]ethyl] piperidinebutanamide (V). Final acylation of the secondary amine (V) with acetyl chloride in chloroform in the presence of triethylamine was carried out at 0 C to provide bidisomide (SC-40230).
| 【1】 Desai, B.N.; Chorvat, R.J.; Rorig, K.J. (G.D. Searle & Co.); Monobasic derivatives of disobutamide. US 4639524 . |
| 【2】 Novotney, R.L.; Woo, C.M.; Yonan, P.K.; Hershenson, F.; Prodan, K.A.; Synthesis and antiarrhythmic activity of alpha-bis[(dialkylamino)alkyl]phenylacetamides. J Med Chem 1980, 23, 10, 1102. |
| 【3】 Chorvat, R.J.; Rorig, K.J.; Fowler, K.W.; Frederick, L.G.; Desai, B.N.; Garthwaite, S.M.; Hatley, F.R.; Synthesis and structure-activity relationships of new series of antiarrhythmic agents: Monobasic derivatives of disobutamide. J Med Chem 1988, 31, 2158. |
| 【4】 Cook, C.S.; Claypool, W.D.Garthwaite, S.M.; Desai, B.N.; Bidisomide. Drugs Fut 1992, 17, 5, 374. |
| 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) | 11434 | 2-(2-Chlorophenyl)-4-piperidinobutanenitrile | C15H19ClN2 | 详情 | 详情 | |
| (II) | 11435 | N-Benzyl-N-(2-chloroethyl)-2-propanamine; N-Benzyl-N-(2-chloroethyl)-N-isopropylamine | C12H18ClN | 详情 | 详情 | |
| (III) | 11436 | 4-[Benzyl(isopropyl)amino]-2-(2-chlorophenyl)-2-(2-piperidinoethyl)butanenitrile | C27H36ClN3 | 详情 | 详情 | |
| (IV) | 11437 | 4-[Benzyl(isopropyl)amino]-2-(2-chlorophenyl)-2-(2-piperidinoethyl)butanamide | C27H38ClN3O | 详情 | 详情 | |
| (V) | 11438 | 2-(2-Chlorophenyl)-4-(isopropylamino)-2-(2-piperidinoethyl)butanamide | C20H32ClN3O | 详情 | 详情 |