新产品编号:128651

Chemical Name: (+)-8-(3-Methylureido)-4-oxo-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine-10-acetic acid
CAS No. 173156-08-6, 173155-70-9 (monohydrochloride), 173155-69-6 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线: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: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.