新产品编号:155545
Chemical Name: (+)-1'-Methylspiro[5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-10,2'-pyrrolidin]-4-one
CAS No. 179174-42-6, 179174-43-7 ((-)-enantiomer), 179174-41-5 (racemate)
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:The known imidazoindenopyrazinone (I) was converted to oxime (II) by treatment with isoamyl nitrite and NaH.Subsequent reduction of oxime (II) by means of zinc and AcOH produced acetamide (III),which was hydrolyzed to amine (IV) upon refluxing in 2 N HCl.After protection of amine (IV) as the N-Boc derivative (V),alkylation with 1-bromo-3-chloropropane (VI) in the presence of NaH gave rise to the spiro derivative (VII).Deprotection of the Boc group of (VII) to give amine (VIII) was effected by treatment with trifluoroacetic acid.Finally,Eschweiler-Clarke reductive alkylation of (VIII) with formaldehyde and formic acid furnished the desired N-methyl derivative.
📌 参考资料/链接：
参考文献标题:Spiro[heterocycle-imidazo[1,2-a]indeno[1,2-e]pyrazine]-4'-ones,preparation thereof and drugs containing same
文献作者:Aloup,J.-C.; Audiau,F.; Barreau,M.; Damour,D.; Genevois-Borella,A.; Jimonet,P.; Mignani,S.; Ribeill,Y.(Aventis Pharma SA)
参考来源:JP 1998508311; US 5777114; WO 9614318
📄 详细内容
合成路线:The known imidazoindenopyrazinone (I) was converted to oxime (II) by treatment with isoamyl nitrite and NaH.Subsequent reduction of oxime (II) by means of zinc and AcOH produced acetamide (III),which was hydrolyzed to amine (IV) upon refluxing in 2 N HCl.After protection of amine (IV) as the N-Boc derivative (V),alkylation with 1-bromo-3-chloropropane (VI) in the presence of NaH gave rise to the spiro derivative (VII).Deprotection of the Boc group of (VII) to give amine (VIII) was effected by treatment with trifluoroacetic acid.Finally,Eschweiler-Clarke reductive alkylation of (VIII) with formaldehyde and formic acid furnished the desired N-methyl derivative.
参考文献标题:Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo
文献作者:Jimonet,P.; Boireau,A.; Chev? M.; Damour,D.; Genevois-Borella,A.; Imperato,A.; Pratt,J.; Randle,J.C.; Ribeill,Y.; Stutzmann,J.M.; Mignani,S.
参考来源:Bioorg Med Chem Lett 1999,9(20),2921