AR-C102222
Chemical Name: 5-(4'-Amino-5',8'-difluoro-1',2'-dihydrospiro[piperidine-4,2'-quinazoline]-1-ylcarbonyl)pyridine-2-carbonitrile
CAS No. 253771-21-0, 190010-48-1 (diHCl)
项目整合开发状态: Preclinical
项目研究机构: AstraZeneca Charnwood (Originator)
合成路线:Displacement of the 2-fluoro group in 2,3,6-trifluorobenzonitrile (I) with aqueous ammonia leads to 2-amino-3,6-difluorobenzonitrile (II).Addition of hydroxylamine to the nitrile (II) in the presence of NaOMe affords benzamidoxime (III).Subsequent catalytic hydrogenation of (III) over Raney nickel furnishes benzamidine (IV).
合成路线:4-Piperidone ethylene ketal (V) is acylated with 6-bromonicotinic acid (VI) employing 1,1'-carbonyldiimidazole to yield amide (VII).The bromide group of (VII) is then displaced with CuCN in hot DMF producing nitrile (VIII).Finally,condensation between N-acylpiperidone (VIII) and amidine (IV) in refluxing EtOH leads to the target spiro quinazoline.
📌 参考资料/链接：
参考文献标题:Pharmaceutically active quinazoline cpds.
文献作者:Hamley,P.R.J.; Pimm,A.D.; Tinker,A.C.; Beaton,H.G.; McInally,T.(AstraZeneca plc)
参考来源:EP 0858451; JP 1999513679; WO 9714686
📄 详细内容
合成路线:Displacement of the 2-fluoro group in 2,3,6-trifluorobenzonitrile (I) with aqueous ammonia leads to 2-amino-3,6-difluorobenzonitrile (II).Addition of hydroxylamine to the nitrile (II) in the presence of NaOMe affords benzamidoxime (III).Subsequent catalytic hydrogenation of (III) over Raney nickel furnishes benzamidine (IV).
合成路线:4-Piperidone ethylene ketal (V) is acylated with 6-bromonicotinic acid (VI) employing 1,1'-carbonyldiimidazole to yield amide (VII).The bromide group of (VII) is then displaced with CuCN in hot DMF producing nitrile (VIII).Finally,condensation between N-acylpiperidone (VIII) and amidine (IV) in refluxing EtOH leads to the target spiro quinazoline.
参考文献标题:1,2-Dihydro-4-quinazolinamines: Potent,highly selective inhibitors of inducible nitric oxide synthase which show antiinflammatory activity in vivo
文献作者:Tinker,A.C.; Beaton,H.G.; Boughton-Smith,N.; Cook,T.R.; Cooper,S.L.; Fraser-Rae,L.; Hallam,K.; Hamley,P.; McInally,T.; Nicholls,D.J.; Pimm,A.D.; Wallace,A.V.
参考来源:J Med Chem 2003,46(6),913
产品链接: CAS No. 253771-21-0››