RPR-117824
Chemical Name: 9-(Carboxymethyl)-4-oxo-5,10-dihydro-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine-2-carboxylic acid
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:Heck coupling of 2-bromophenylacetic acid (I) with acrylic acid (II) produces the dicarboxylic acid adduct (III).Subsequent catalytic hydrogenation of the olefinic double bond of (III) gives rise to the saturated diacid (IV).Then,Friedel-Crafts intramolecular cyclization of (IV) in hot H2SO4 affords indanone (V).Bromination of (V) in AcOH yields 2-bromo-1-oxoindan-4-ylacetic acid (VI).Esterification of (VI) is carried out via conversion to the corresponding acid chloride,followed by quenching with EtOH to provide the ethyl ester (VII).Condensation of bromo indanone (VII) with diethyl imidazole-2,4-dicarboxylate (VIII) furnishes the imidazolyl indanone (IX).Ring closure of keto ester (IX) with ammonium acetate in refluxing AcOH produces the tetracyclic compound (X).The ethyl ester groups of (X) are finally hydrolyzed under basic conditions to yield the title dicarboxylic acid.
📌 参考资料/链接：
参考文献标题:5H,10H-Imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivs.,preparation thereof,intermediates thereof and drugs containing same
文献作者:Aloup,J.-C.; Bouquerel,J.; Damour,D.; Hardy,J.-C.; Jimonet,P.; Manfre,M.; Mignani,S.; Nemecek,P.(Aventis Pharma SA)
参考来源:EP 0880522; FR 2743366; JP 2000505073; US 5990108; WO 9725328
📄 详细内容
合成路线:Heck coupling of 2-bromophenylacetic acid (I) with acrylic acid (II) produces the dicarboxylic acid adduct (III).Subsequent catalytic hydrogenation of the olefinic double bond of (III) gives rise to the saturated diacid (IV).Then,Friedel-Crafts intramolecular cyclization of (IV) in hot H2SO4 affords indanone (V).Bromination of (V) in AcOH yields 2-bromo-1-oxoindan-4-ylacetic acid (VI).Esterification of (VI) is carried out via conversion to the corresponding acid chloride,followed by quenching with EtOH to provide the ethyl ester (VII).Condensation of bromo indanone (VII) with diethyl imidazole-2,4-dicarboxylate (VIII) furnishes the imidazolyl indanone (IX).Ring closure of keto ester (IX) with ammonium acetate in refluxing AcOH produces the tetracyclic compound (X).The ethyl ester groups of (X) are finally hydrolyzed under basic conditions to yield the title dicarboxylic acid.
参考文献标题:9-Carboxymethyl-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one-2-carbocylic acid (RPR117824): Selective anticonvulsive and neuroprotective AMPA antagonist
文献作者:Mignani,S.; Bohme,G.A.; Birraux,G.; Boireau,A.; Jimonet,P.; Damour,D.; Genevois-Borella,A.; Debono,M.W.; Pratt,J.; Vuilhorgne,M.; Wahl,F.; Stutzmann,J.M.
参考来源:Bioorg Med Chem 2002,10(5),1627