|
【结 构 式】 
|
【药物名称】Gepirone hydrochloride, ORG-33062, MJ-13805, BMY-13805, Variza, Ariza 【化学名称】4,4-Dimethyl-1-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,6-piperidinedione hydrochloride 【CA登记号】83928-66-9, 83928-76-1 (free base) 【 分 子 式 】C19H30ClN5O2 【 分 子 量 】395.93625 |
【开发单位】Bristol-Myers Squibb (Originator), Organon (Not Determined) 【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1A Receptor Agonists |
合成路线1
The quaternary salt (II), prepared from 1-(pyrimidin-2-yl)piperazine (I) and 1,4-dibromobutane (A), undergoes reaction with 3,3-dimethylglutarimide (III) in the presence of potassium carbonate in refluxing xylene to afford the free base (IV), which is isolated by acid extraction and basification of the extract. Treatment of the free base with HCl in isopropanol affords ttle compound as the monohydrochloride.
| 【1】 Temple, D.L. Jr. (Bristol-Myers Squibb Co.); 2-[4-[(4,4-Dialkyl-2,6-piperidinedion-1-yl)butyl]-1-piperazinyl]pyrimidines. BE 0895504; CH 656383; DE 3248160; FR 2518993; GB 2114122; JP 1983118582; JP 1994293753; US 4423049 . |
| 【2】 Eison, M.S.; Yevich, J.P.; Farney, R.F.; Gepirone Hydrochloride. Drugs Fut 1985, 10, 6, 456. |
| 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) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
| (I) | 11175 | 2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine | 20980-22-7 | C8H12N4 | 详情 | 详情 |
| (II) | 29661 | 8-(2-pyrimidinyl)-8-aza-5-azoniaspiro[4.5]decane bromide | C12H19BrN4 | 详情 | 详情 | |
| (III) | 29662 | 4,4-dimethyl-2,6-piperidinedione | 1123-40-6 | C7H11NO2 | 详情 | 详情 |
合成路线2
This compound has been obtained by two related ways: The reduction of 4-[4-(2-pyrimidinyl)piperazin-1-yl]butyronitrile (I) by means of RaNi and hydrazine in isopropanol gives 4-[4-(2-pyrimidinyl)piperazin-1-yl]butylamine (II), which is then condensed with 3,3-dimethylglutaric anhydride (III) in refluxing xylene or refluxing toluene to yield the target glutarimide derivative. Alternatively, the condensation of N-(4-bromobutyl)-3,3-dimethylglutarimide (IV) with 1-(2-pyrimidinyl)piperazine (V) by means of K2CO3 in refluxing acetonitrile also yields the target glutarimide derivative.
| 【1】 Yevich, J.P.; et al.; Buspirone analogues. 1. Structure-activity relationships in a series of N-aryl- and heteroarylpiperazine derivatives. J Med Chem 1983, 26, 2, 194. |
| 【2】 Temple, D.L. Jr. (Bristol-Myers Squibb Co.); 2-[4-[(4,4-Dialkyl-2,6-piperidinedion-1-yl)butyl]-1-piperazinyl]pyrimidines. BE 0895504; CH 656383; DE 3248160; FR 2518993; GB 2114122; JP 1983118582; JP 1994293753; US 4423049 . |
| 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) | 11180 | 4-[4-(2-Pyrimidinyl)piperazino]butanenitrile | C12H17N5 | 详情 | 详情 | |
| (II) | 11181 | 4-[4-(2-Pyrimidinyl)piperazino]butylamine; 4-[4-(2-Pyrimidinyl)piperazino]-1-butanamine | 33386-20-8 | C12H21N5 | 详情 | 详情 |
| (III) | 25549 | 4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione | 4160-82-1 | C7H10O3 | 详情 | 详情 |
| (IV) | 56851 | 1-(4-bromobutyl)-4,4-dimethyl-2,6-piperidinedione | C11H18BrNO2 | 详情 | 详情 | |
| (V) | 11175 | 2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine | 20980-22-7 | C8H12N4 | 详情 | 详情 |