ACEA-762, ACEA-0762-药物合成数据库

【药物名称】ACEA-762, ACEA-0762

化学结构式(Chemical Structure):

参考文献No.	30605
标题:	Aza and aza (N-oxy) analogs of glycine/NMDA receptor antagonists
作者:	Keana, J.F.W.; Cai, S.X.; Martin, V.V.; Zhou, Z.-L.; Navratil, J.M. (Oregon Health Sciences University)
来源:	EP 0805809; US 5801183; WO 9622990

合成路线图解说明: Nitration of 2-amino-5-chloropyridine (I) in hot sulfuric acid afforded (II). Diazotization of amine (II) in the presence of Br2 and HBr produced the bromopyridine (III), and subsequent displacement of the bromide of (III) with cuprous cyanide at 150 C yielded the picolinonitrile (IV). Catalytic hydrogenation of the nitro group of (IV) in the presence of Raney-Ni gave rise to the amino amide (V), which was further hydrolyzed to acid (VI) using conc. HCl. Fischer esterification of acid (VI) with EtOH and H2SO4 furnished the ethyl ester (VII). Acid chloride (IX), prepared from m-phenoxyphenylacetic acid (VIII) and oxalyl chloride, was then condensed with amino ester (VII) to produce amide (X). Finally, cyclization of (X) in the presence of potassium hexamethyldisilazide yielded the title naphthyridinone.

参考文献No.	629150
标题:	Synthesis and SAR of 5-,6-,7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-ones as NMDA/glycine site antagonists
作者:	Zhou, Z.-L.; Navratil, J.M..; Cai, S.X.; Whittemore, E.R.; Espitia, S.A.; Hawkinson, J.E.; Tran, M.; Woodward, R.M.; Weber, E.; Keana, J.F.
来源:	Bioorg Med Chem 2001,9(8),2061

合成路线图解说明: Nitration of 2-amino-5-chloropyridine (I) in hot sulfuric acid afforded (II). Diazotization of amine (II) in the presence of Br2 and HBr produced the bromopyridine (III), and subsequent displacement of the bromide of (III) with cuprous cyanide at 150 C yielded the picolinonitrile (IV). Catalytic hydrogenation of the nitro group of (IV) in the presence of Raney-Ni gave rise to the amino amide (V), which was further hydrolyzed to acid (VI) using conc. HCl. Fischer esterification of acid (VI) with EtOH and H2SO4 furnished the ethyl ester (VII). Acid chloride (IX), prepared from m-phenoxyphenylacetic acid (VIII) and oxalyl chloride, was then condensed with amino ester (VII) to produce amide (X). Finally, cyclization of (X) in the presence of potassium hexamethyldisilazide yielded the title naphthyridinone.