Igmesine hydrochloride, CI-1019, JO-1784

(E)-(+)-N-(环丙基甲基)-α-乙基-N-甲基-α-(3-苯基-2-丙基)-苯甲基胺盐酸盐 伊格美新 Chemical Name: (+)-N-(Cyclopropylmethyl)-N-[1-ethyl-1,4-diphenyl-3(E)-butenyl]-N-methylamine hydrochloride
CAS No. 130152-35-1, 140850-73-3 (free base)
项目整合开发状态: Phase II
项目研究机构: Jouveinal (Originator), Pfizer (Originator)
合成路线: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: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.