新产品编号:837387
Chemical Name: N-(1,3-Benzodioxol-5-ylmethyl)-6-fluoro-7-(1-piperazinyl)quinazolin-4-amine hydrochloride
CAS No. 333400-60-5 (free base)
项目整合开发状态: Preclinical
项目研究机构: Japan Energy (Originator)
合成路线:4,5-Difluoroanthranilic acid (I) is coupled with ammonium hydroxide upon activation with diphenylphosphoryl chloride to furnish the amino benzamide (II) (1).Subsequent cyclization of anthranilamide (II) with trimethyl orthoformate produces quinazolone (III),which is converted into the chloroquinazoline (IV) by using either POCl3 or SOCl2.Condensation of (IV) with 3,4-methylenedioxy-benzylamine (V) affords the aminoquinazoline derivative (VI).Then,regioselective displacement of the 7-fluorine atom in (VI) with piperazine (VII) in hot 1-butanol gives rise to the title compound (1,2).
📌 参考资料/链接：
参考文献标题:Novel quinazoline derivs.
文献作者:Matsumoto,M.; Isobe,Y.; Nagasaki,T.; Obara,F.; Tobe,M.; Tomizawa,H.(Japan Energy Corp.)
参考来源:EP 1229025; WO 0125218
📄 详细内容
合成路线:4,5-Difluoroanthranilic acid (I) is coupled with ammonium hydroxide upon activation with diphenylphosphoryl chloride to furnish the amino benzamide (II) (1).Subsequent cyclization of anthranilamide (II) with trimethyl orthoformate produces quinazolone (III),which is converted into the chloroquinazoline (IV) by using either POCl3 or SOCl2.Condensation of (IV) with 3,4-methylenedioxy-benzylamine (V) affords the aminoquinazoline derivative (VI).Then,regioselective displacement of the 7-fluorine atom in (VI) with piperazine (VII) in hot 1-butanol gives rise to the title compound (1,2).
参考文献标题:Structure-activity relationships of 6-fluoroquinazolines: Dual-acting compounds with inhibitory activities toward both TNF-alpha production and T cell proliferation
文献作者:Tobe,M.; Isobe,Y.; Tomizawa,H.; Nagasaki,T.; Obara,F.; Hayashi,H.
参考来源:Bioorg Med Chem 2003,11(4),609