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【结 构 式】 
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【分子编号】18340 【品名】N(1),N(2)-dibenzyl-1,2-ethanediamine; N-benzyl-N-[2-(benzylamino)ethyl]amine; N,N-Dibenzylethylendiamine 【CA登记号】140-28-3 |
【 分 子 式 】C16H20N2 【 分 子 量 】240.34828 【元素组成】C 79.96% H 8.39% N 11.66% |
合成路线1
该中间体在本合成路线中的序号：(I)A new synthesis of centperazine has been reported: The cyclization of N,N'-dibenzylethylenediamine (I) with 2,3-dibromopropionitrile (II) by means of triethylamine in refluxing toluene gives 2-(1,4-dibenzylpiperazin-2-yl)acetonitrile (III), which is reduced with H2 over RaNi in methanol to yield the corresponding ethylamine (IV). Acylation of (IV) with ethyl chloroformate (V) and triethylamine in dichloromethane affords the corresponding carbamate (VI), which is debenzylated by hydrogenation with H2 over Pd/C in acetic acid, giving N-[2-(2-piperazinyl)ethyl]carbamic acid ethyl ester (VII). The cyclization of (VII) by means of sodium ethoxide in hot ethanol yields perhydropyrazino[1,2-c]pyrimidin-6-one (VIII), which is methylated with formaldehyde-formic acid to the 2-methyl derivative (IX). Finally, this compound is ethylated with ethyl iodide, tetrabutylammonium bromide and KOH in THF.
| 【1】 Chatterjee, S.K.; Sahu, D.P.; Sengupta, S.; A convenient synthesis of centperazine, an antifilarial candidate drug. Liebigs Ann Chem 1993, 4, 4, 437. |
| 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) | 18340 | N(1),N(2)-dibenzyl-1,2-ethanediamine; N-benzyl-N-[2-(benzylamino)ethyl]amine; N,N-Dibenzylethylendiamine | 140-28-3 | C16H20N2 | 详情 | 详情 |
| (II) | 10364 | 3,4-dibromobutanenitrile | C4H5Br2N | 详情 | 详情 | |
| (III) | 10365 | 2-(1,4-Dibenzyl-2-piperazinyl)acetonitrile | C20H23N3 | 详情 | 详情 | |
| (IV) | 10366 | 2-(1,4-Dibenzyl-2-piperazinyl)ethylamine; 2-(1,4-Dibenzyl-2-piperazinyl)-1-ethanamine | C20H27N3 | 详情 | 详情 | |
| (VI) | 10367 | ethyl N-[2-(1,4-dibenzyl-2-piperazinyl)ethyl]carbamate | C23H31N3O2 | 详情 | 详情 | |
| (VII) | 10368 | ethyl N-[2-(2-piperazinyl)ethyl]carbamate | C9H19N3O2 | 详情 | 详情 | |
| (VIII) | 10369 | Octahydro-6H-pyrazino[1,2-c]pyrimidin-6-one | C7H13N3O | 详情 | 详情 | |
| (IX) | 10370 | 2-Methyloctahydro-6H-pyrazino[1,2-c]pyrimidin-6-one | C8H15N3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Condensation of N,N'-dibenzylethylenediamine (I) with ethyl 2,3-dibromopropionate (II) in the presence of Et3N in toluene at 80 C gave, after acidification, piperazine (III). Then, hydrogenolytic N-debenzylation in the presence of Pd/C provided ethyl piperazine-2-carboxylate (IV), which was selectively alkylated at position 4 with 1 equivalent of triphenylmethyl chloride in the presence of Et3N at -10 C to give (V). Subsequent alkylation with 2,4-dichlorobenzyl chloride (VI) in the presence of K2CO3 and a catalytic amount of KI provided (VII). Removal of the N-trityl group by treatment with HCl in either acetone or ethanol afforded piperarine (VIII), which was N-methylated by reaction with formaldehyde and formic acid in refluxing MeOH. Finally, the resulting compound (IX) was converted into the imidazoline on treatment with ethylenediamine and trimethylaluminum in refluxing toluene.
| 【1】 Rondu, F.; et al.; Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 1. Synthesis and biological activities of N-benzyl-N'-(arylalkyl)-2-(4', 5'-dihydro-1'H-imidazol-2'-yl)piperazines. J Med Chem 1997, 40, 23, 3793. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 | |
| (I) | 18340 | N(1),N(2)-dibenzyl-1,2-ethanediamine; N-benzyl-N-[2-(benzylamino)ethyl]amine; N,N-Dibenzylethylendiamine | 140-28-3 | C16H20N2 | 详情 | 详情 |
| (II) | 18341 | ethyl 2,3-dibromopropanoate | 3674-13-3 | C5H8Br2O2 | 详情 | 详情 |
| (III) | 18342 | ethyl 1,4-dibenzyl-2-piperazinecarboxylate | 72351-59-8 | C21H26N2O2 | 详情 | 详情 |
| (IV) | 18343 | ethyl 2-piperazinecarboxylate | 89941-07-1 | C7H14N2O2 | 详情 | 详情 |
| (V) | 18344 | ethyl 4-trityl-2-piperazinecarboxylate | C26H28N2O2 | 详情 | 详情 | |
| (VI) | 18345 | 2,4-Dichlorobenzyl chloride; 2,4-Dichloro-1-(chloromethyl)benzene | 94-99-5 | C7H5Cl3 | 详情 | 详情 |
| (VII) | 18346 | ethyl 1-(2,4-dichlorobenzyl)-4-trityl-2-piperazinecarboxylate | C33H32Cl2N2O2 | 详情 | 详情 | |
| (VIII) | 18347 | ethyl 1-(2,4-dichlorobenzyl)-2-piperazinecarboxylate | C14H18Cl2N2O2 | 详情 | 详情 | |
| (IX) | 18348 | ethyl 1-(2,4-dichlorobenzyl)-4-methyl-2-piperazinecarboxylate | C15H20Cl2N2O2 | 详情 | 详情 |