-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	37287
标题:	Imidazo (1,2-a)-indeno (1,2-e) pyrazin-4-one derivs. and pharmaceutical compsns. containing same
作者:	Genevois-Borella, A.; Aloup, J.-C.; Audiau, F.; Barreau, M.; Mignani, S.; Ribeill, Y.; Damour, D.; Jimonet, P. (Aventis Pharma SA)
来源:	US 5807859; WO 9526350

合成路线图解说明: The condensation of 2-bromo-1-indanone (I) with 1-methylimidazole-2-carboxamide (II) in hot DMF produced the tetracyclic ammonium salt (III), which was further demethylated to (IV) by means of imidazole at 160 C. Regioselective nitration of (IV) employing KNO3 in H2SO4 produced nitro derivative (V), which was reduced to amine (VI) by catalytic hydrogenation over Pd/C. Amine (VI) was converted to urea (VII) by treatment with methyl isocyanate. Subsequent base-catalyzed condensation of (VII) with glyoxylic acid monohydrate (VIII) produced hydroxyacid (IX). This was dehydrated with ZnCl2 and acetic anhydride to give unsaturated acid (X), which was finally hydrogenated over Pd/C to furnish the title compound.

合成路线图解说明: The tetracyclic imidazoindenopyrazinone (IV) was obtained by condensation of 2-bromoindanone (I) with 1-methylimidazole-2-carboxamide (II), followed by demethylation of the resulting imidazolium salt (III) in molten imidazole at 160 C (1). Reaction of (IV) with isoamyl nitrite in the presence of NaH produced oxime (V), which was reduced with zinc powder in acetic acid to yield acetamide (VI). Regioselective methylation of (VI) using methyl iodide and NaH gave (VII). Subsequent nitration of (VII) by means of KNO3 and H2SO4 afforded the 8-nitro derivative (VIII), which was reduced to amine (IX) by hydrogenation over Pd/C. Condensation of amine (IX) with methyl isocyanate in DMF produced urea (X). Finally, the acetamido group of (X) was hydrolyzed in refluxing 6 M HCl.

参考文献No.	590743
标题:	8-Methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-ones: Highly in vivo potent and selective AMPA receptor antagonists
作者:	Jimonet, P.; Chev? M.; Bohme, G.A.; Boireau, A.; Damour, D.; Debono, M.W.; Genevois-Borella, A.; Imperato, A.; Pratt, J.; Randle, J.C.; Ribeill, Y.; Stutzmann, J.M.; Vuilhorgne, M.; Mignani, S.
来源:	Bioorg Med Chem 2000,8(8),2211

合成路线图解说明: The tetracyclic imidazoindenopyrazinone (IV) was obtained by condensation of 2-bromoindanone (I) with 1-methylimidazole-2-carboxamide (II), followed by demethylation of the resulting imidazolium salt (III) in molten imidazole at 160 C (1). Reaction of (IV) with isoamyl nitrite in the presence of NaH produced oxime (V), which was reduced with zinc powder in acetic acid to yield acetamide (VI). Regioselective methylation of (VI) using methyl iodide and NaH gave (VII). Subsequent nitration of (VII) by means of KNO3 and H2SO4 afforded the 8-nitro derivative (VIII), which was reduced to amine (IX) by hydrogenation over Pd/C. Condensation of amine (IX) with methyl isocyanate in DMF produced urea (X). Finally, the acetamido group of (X) was hydrolyzed in refluxing 6 M HCl.