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【结 构 式】 
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【分子编号】58179 【品名】6-({[1-(ethoxycarbonyl)-1H-indazol-3-yl]carbonyl}amino)-4-methyl-1-(3-methylbenzyl)-3,4,5,6-tetrahydro-2H-1,4-diazepin-1-ium 【CA登记号】 |
【 分 子 式 】C25H30N5O3 【 分 子 量 】448.5451 【元素组成】C 66.94% H 6.74% N 15.61% O 10.7% |
合成路线1
该中间体在本合成路线中的序号：(IX)The reductocondensation of ethanolamine (I) with 3-methylbenzaldehyde (II) by means of NaBH4 gives N-(3-methylbenzyl)ethanolamine (III), which is treated with SOCl2 to yield the 2-chloroethyl derivative (IV). The reaction of (IV) with methylamine (V) affords N-methyl-N'-(3-methylbenzyl)ethane-1,2-diamine (VI), which is condensed with the pyrazole-carboxamide derivative (VII) to provide the unstable compound (VIII)?? (IX). The reduction of (IX) with NaBH4 gives the racemic amide (X), which is submitted to optical resolution by preferential crystallization to yield the (R)-isomer (XI) (1,2). The hydrogenation of (XI) with H2 over Pd/C in ethanol affords the debenzylated compound (XII), which is alkylated by reductocondensation with acetaldehyde (XIII) and NaBH4 in methanol to provide the chiral N-(1-ethyl-4'-methylperhydro-1,4-diazepin-6-(R)-yl)-1H-pyrazole-3-carboxamide (XIV). Finally, this compound is treated with refluxing aqueous HCl to give the corresponding 6(R)-amino derivative (XV).
| 【2】 Hirokawa, Y.; et al.; Synthesis and structure-activity relationships of 4-amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide derivatives, novel and potent serotonin 5-HT3 and dopamine D2 receptors dual antagonist. Chem Pharm Bull 2002, 50, 7, 941. |
| 【1】 Harada, H.; et al.; Synthesis and resolution of (±)-N-[1-methyl-4-(3-methylbenzyl)hexahydro-1H-1,4-diazepin-6-yl]-1H-indazole-3-carboxamide by preferential crystallization. Tetrahedron Asymmetry 1997, 8, 14, 2367. |
| 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) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (II) | 41077 | 3-methylbenzaldehyde | 620-23-5 | C8H8O | 详情 | 详情 |
| (III) | 58175 | 2-[(3-methylbenzyl)amino]-1-ethanol | C10H15NO | 详情 | 详情 | |
| (IV) | 58176 | 2-chloro-N-(3-methylbenzyl)-1-ethanamine; N-(2-chloroethyl)-N-(3-methylbenzyl)amine | C10H14ClN | 详情 | 详情 | |
| (V) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |
| (VI) | 54009 | N~1~-methyl-N~2~-(3-methylbenzyl)-1,2-ethanediamine; N-methyl-N-{2-[(3-methylbenzyl)amino]ethyl}amine | n/a | C11H18N2 | 详情 | 详情 |
| (VII) | 58177 | ethyl 3-{[(1-formylvinyl)amino]carbonyl}-1H-indazole-1-carboxylate | C14H13N3O4 | 详情 | 详情 | |
| (VIII) | 58178 | ethyl 3-({[1-formyl-2-(methyl{2-[(3-methylbenzyl)amino]ethyl}amino)ethyl]amino}carbonyl)-1H-indazole-1-carboxylate | C25H31N5O4 | 详情 | 详情 | |
| (IX) | 58179 | 6-({[1-(ethoxycarbonyl)-1H-indazol-3-yl]carbonyl}amino)-4-methyl-1-(3-methylbenzyl)-3,4,5,6-tetrahydro-2H-1,4-diazepin-1-ium | C25H30N5O3 | 详情 | 详情 | |
| (X) | 58180 | N-[1-methyl-4-(3-methylbenzyl)-1,4-diazepan-6-yl]-1H-indazole-3-carboxamide | C22H27N5O | 详情 | 详情 | |
| (XI) | 58181 | N-[(6S)-1-methyl-4-(3-methylbenzyl)-1,4-diazepan-6-yl]-1H-indazole-3-carboxamide | C22H27N5O | 详情 | 详情 | |
| (XII) | 58182 | N-[(6S)-1-methyl-1,4-diazepan-6-yl]-1H-indazole-3-carboxamide | C14H19N5O | 详情 | 详情 | |
| (XIII) | 11974 | Acetaldehyde | 75-07-0 | C2H4O | 详情 | 详情 |
| (XIV) | 58183 | N-[(6S)-1-ethyl-4-methyl-1,4-diazepan-6-yl]-1H-indazole-3-carboxamide | C16H23N5O | 详情 | 详情 | |
| (XV) | 17802 | (6S)-1-ethyl-4-methyl-1,4-diazepan-6-ylamine; (6S)-1-ethyl-4-methyl-1,4-diazepan-6-amine | C8H19N3 | 详情 | 详情 |