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【结 构 式】 
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【分子编号】62397 【品名】6,11-dihydro-5H-dibenzo[b,e]azepin-6-yl-N-methylmethanamine; N-(6,11-dihydro-5H-dibenzo[b,e]azepin-6-ylmethyl)-N-methylamine 【CA登记号】 |
【 分 子 式 】C16H18N2 【 分 子 量 】238.3324 【元素组成】C 80.63% H 7.61% N 11.75% |
合成路线1
该中间体在本合成路线中的序号：(VI)The title compound has been synthesized by several procedures. Acylation of 2-benzylaniline (I) by chloroacetyl chloride (II) gave chloroacetamide (III). Subsequent cyclization of amide (III) under Vilsmeier conditions furnished the dibenzoazepine (IV). Nucleophilic substitution of the chlorine atom of (IV) by methylamine led to amine (V). The imine function of (V) was reduced with either LiAlH4 or NaBH4 to the diamine (VI), which was further converted into the fused diketopiperazine (VII) upon heating with diethyl oxalate. The amide groups of (VII) were then reduced by means of borane in THF, yielding the target tetracyclic diamine, which was finally isolated as the corresponding hydrochloride salt
| 【1】 van der Burg, W.J.; et al.; A novel type of substituted piperazine with high antiserotonin potency. J Med Chem 1970, 13, 1, 35. |
| 【2】 van der Burg, W.J.; Delobelle, J.; Polycyclic piperazines. US 3534041 . |
| 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) | 62393 | 2-benzylaniline; 2-benzylphenylamine | 28059-64-5 | C13H13N | 详情 | 详情 |
| (II) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (III) | 62394 | N-(2-benzylphenyl)-2-chloroacetamide | C15H14ClNO | 详情 | 详情 | |
| (IV) | 62395 | 6-(chloromethyl)-11H-dibenzo[b,e]azepine | 21535-44-4 | C15H12ClN | 详情 | 详情 |
| (V) | 62396 | 11H-dibenzo[b,e]azepin-6-yl-N-methylmethanamine; N-(11H-dibenzo[b,e]azepin-6-ylmethyl)-N-methylamine | C16H16N2 | 详情 | 详情 | |
| (VI) | 62397 | 6,11-dihydro-5H-dibenzo[b,e]azepin-6-yl-N-methylmethanamine; N-(6,11-dihydro-5H-dibenzo[b,e]azepin-6-ylmethyl)-N-methylamine | C16H18N2 | 详情 | 详情 | |
| (VII) | 62398 | 2-methyl-1,2,10,14b-tetrahydrodibenzo[c,f]pyrazino[1,2-a]azepine-3,4-dione | C18H16N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Treatment of alpha-chlorophenylacetyl chloride (VIII) with methylamine provided the corresponding chloro amide (IX), which was subsequently condensed with 2-aminobenzyl alcohol (X) to afford amino alcohol (XI). Cyclization of (XI) in the presence of AlCl3 led to the dibenzoazepine (XII). This was converted to the tetracyclic compound (XIV) by reaction with dibromoethane (XIII) in the presence of Na2CO3. Reduction of the amide carbonyl group of (XIV) by means of LiAlH4 furnished the title compound. In a related strategy, amide (XII) was initially reduced to diamine (VI) by using LiAlH4. Subsequent condensation of (VI) with dibromoethane (XIII) led to the target tetracyclic derivative
| 【1】 Haider, A.; Bollinger, H.; Fischer, A. (Sochinaz SA); Process for the preparation of a tetracyclic compound and application of this process for the preparation of 1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin. FR 2647114 . |
| 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) | 62397 | 6,11-dihydro-5H-dibenzo[b,e]azepin-6-yl-N-methylmethanamine; N-(6,11-dihydro-5H-dibenzo[b,e]azepin-6-ylmethyl)-N-methylamine | C16H18N2 | 详情 | 详情 | |
| (VIII) | 62399 | 2-chloro-2-phenylacetyl chloride | C8H6Cl2O | 详情 | 详情 | |
| (IX) | 62400 | 2-chloro-N-methyl-2-phenylacetamide | C9H10ClNO | 详情 | 详情 | |
| (X) | 18619 | (2-aminophenyl)methanol; 2-Amino-benzenemethanol；2-Hydroxymethyl aniline;2-aminobenzyl alcohol;o-Aminobenzyl 2-aminobenzylalcohol;alcohol; 2-aminobenzenemethanol; 2-aminobenzyl alcohol | 5344-90-1 | C7H9NO | 详情 | 详情 |
| (XI) | 62401 | 2-[2-(hydroxymethyl)anilino]-N-methyl-2-phenylacetamide | C16H18N2O2 | 详情 | 详情 | |
| (XII) | 62402 | N-methyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide | C16H16N2O | 详情 | 详情 | |
| (XIII) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (XIV) | 62403 | 2-methyl-3,4,10,14b-tetrahydrodibenzo[c,f]pyrazino[1,2-a]azepin-1(2H)-one | C18H18N2O | 详情 | 详情 |