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【结 构 式】 
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【分子编号】21134 【品名】1-[(E)-1-ethyl-1-isocyanato-4-phenyl-3-butenyl]benzene; (E)-1-ethyl-1,4-diphenyl-3-butenyl isocyanate 【CA登记号】 |
【 分 子 式 】C19H19NO 【 分 子 量 】277.366 【元素组成】C 82.28% H 6.9% N 5.05% O 5.77% |
合成路线1
该中间体在本合成路线中的序号：(V)1) Racemic igmesine has been synthesized as follows: Alkylation of 2-phenylbutyric acid (I) with cinnamyl bromide (II) by means of butyllithium in THF gives 2-ethyl-2,5-diphenyl-4-pentenoic acid (III), which is treated with sodium azide and phenyl dichlorophosphate in dichloromethane, yielding the corresponding azide (IV). The Curtius rearrangement of (IV) in refluxing toluene affords the isocyanate (V), which is reduced with LiAlH4/AlCl3 in THF to give N-(1-ethyl-1,4-diphenyl-3-butenyl)-N-metylamine (VI). The acylation of (VI) with cyclopropanecarbonyl chloride (VII) by means of triethylamine in dichloromethane yields the corresponding amide (VIII), which is finally reduced with LiAlH4/AlCl3 in THF/ethyl ether.
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【1】
Sorbera, L.A.; Castaner, J.; Silvestre, J.S.; Igmesine Hydrochloride |
| 【2】 Aubard, G.; Calvet, A.; Gouret, C.; Grouhel, A.; Jacobelli, H.; Junien, J.-L. (Jouveinal SA); Disubstituted benzylamines, process for their preparation, their use as medicament and their synthesis intermediates. EP 0361990; EP 0362001; FR 2636625; US 5034419; US 5089639 . |
| 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) | 21130 | 2-Phenylbutyric acid; alpha-Ethylbenzeneacetic acid | 90-27-7 | C10H12O2 | 详情 | 详情 |
| (II) | 21131 | 1-[(E)-3-bromo-1-propenyl]benzene | 4392-24-9 | C9H9Br | 详情 | 详情 |
| (III) | 21132 | (E)-2-ethyl-2,5-diphenyl-4-pentenoic acid | C19H20O2 | 详情 | 详情 | |
| (IV) | 21133 | (E)-2-ethyl-2,5-diphenyl-4-pentenoyl azide | C19H19N3O | 详情 | 详情 | |
| (V) | 21134 | 1-[(E)-1-ethyl-1-isocyanato-4-phenyl-3-butenyl]benzene; (E)-1-ethyl-1,4-diphenyl-3-butenyl isocyanate | C19H19NO | 详情 | 详情 | |
| (VI) | 21135 | (rac)-[(E)-N-methyl-3,6-diphenyl-5-hexen-3-amine]; (rac)-[N-[(E)-1-ethyl-1,4-diphenyl-3-butenyl]-N-methylamine] | C19H23N | 详情 | 详情 | |
| (VII) | 14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 |
| (VIII) | 21137 | (rac)-[N-[(E)-1-ethyl-1,4-diphenyl-3-butenyl]-N-methylcyclopropanecarboxamide] | C23H27NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)2) Igmesine has been synthesized as follows: Hydrolysis of the previously described isocyanate (V) with HCl in refluxing THF/water gives the corresponding amine (IX), which is submitted to optical resolution with L-(-)tartaric acid, yielding the (+)-isomer (+)-(IX). The acylation of (+)-(IX) with formic acid and carbonyldiimidazole (CDI) affords the expected formamide (+)-(X), which is reduced with AlAl3/LiAlH4 in THF/ethyl ether, giving (-)-N-(1-ethyl-1,4-diphenyl-3-butenyl)-N-metylamine (-)-(VI). The condensation of (-)-(VI) with cyclopropanecarbonyl chloride (VII) by means of triethylamine in dichloromethane yields the corresponding amide (+)-(VIII), which is finally reduced with AlCl3/LiAlH4 in THF/ethyl ether.
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【1】
Sorbera, L.A.; Castaner, J.; Silvestre, J.S.; Igmesine Hydrochloride |
| 【2】 Aubard, G.; Calvet, A.; Gouret, C.; Grouhel, A.; Jacobelli, H.; Junien, J.-L. (Jouveinal SA); Disubstituted benzylamines, process for their preparation, their use as medicament and their synthesis intermediates. EP 0361990; EP 0362001; FR 2636625; US 5034419; US 5089639 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (+)-(IX) | 64672 | (E)-1-ethyl-1,4-diphenyl-3-butenylamine; (E)-3,6-diphenyl-5-hexen-3-amine | C18H21N | 详情 | 详情 | |
| (+)-(X) | 64673 | (E)-1-ethyl-1,4-diphenyl-3-butenylformamide | C19H21NO | 详情 | 详情 | |
| (-)-(VI) | 64674 | (E)-N-methyl-3,6-diphenyl-5-hexen-3-amine; N-[(E)-1-ethyl-1,4-diphenyl-3-butenyl]-N-methylamine | C19H23N | 详情 | 详情 | |
| (+)-(VIII) | 64675 | N-[(E)-1-ethyl-1,4-diphenyl-3-butenyl]-N-methylcyclopropanecarboxamide | C23H27NO | 详情 | 详情 | |
| (V) | 21134 | 1-[(E)-1-ethyl-1-isocyanato-4-phenyl-3-butenyl]benzene; (E)-1-ethyl-1,4-diphenyl-3-butenyl isocyanate | C19H19NO | 详情 | 详情 | |
| (VII) | 14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 |
| (IX) | 21138 | (rac)-(E)-3,6-diphenyl-5-hexen-3-amine; (rac)-[(E)-1-ethyl-1,4-diphenyl-3-butenylamine] | C18H21N | 详情 | 详情 |