Igmesine hydrochloride, CI-1019, JO-1784-药物合成数据库

【药物名称】Igmesine hydrochloride, CI-1019, JO-1784

化学结构式(Chemical Structure):

参考文献No.	13001
标题:	Disubstituted benzylamines, process for their preparation, their use as medicament and their synthesis intermediates
作者:	Aubard, G.; Calvet, A.; Gouret, C.; Grouhel, A.; Jacobelli, H.; Junien, J.-L. (Jouveinal SA)
来源:	EP 0361990; EP 0362001; FR 2636625; US 5034419; US 5089639

合成路线图解说明: 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.

合成路线图解说明: 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.

参考文献No.	474038
标题:	Igmesine Hydrochloride
作者:	Sorbera, L.A.; Casta馿r, J.; Silvestre, J.S.
来源:	Drugs Fut 1999,24(2),133

合成路线图解说明: 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.

合成路线图解说明: 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.