-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	546075
标题:	Novel prodrug approach for tertiary amines: Synthesis and preliminary evaluation of N-phosphonooxymethyl prodrugs
作者:	Krise, J.P.; Zygmunt, J.; Georg, G.I.; Stella, V.J.
来源:	J Med Chem 1999,42(16),3094

合成路线图解说明: Treatment of cinnarizine (I) with phosphate (IV) in acetonitrile in the presence of the proton scavenger 1,2,2,6,6-pentamethylpiperidine affords cinarizinium chloride (II), which is finally treated with TFA in benzene to yield the target trifluoroacetate derivative. Phosphate (IV) can be obtained from phosphite (III) by first treatment with KHCO3 and KMnO4 followed by conversion to tetramethylammonium di-tert-butylphosphate by means of tetramethylammonium hydroxide and final treatment with chloroiodomethane (A) in refluxing dimethoxyethane.

合成路线图解说明: Loxapine (I) is treated with phosphate (IV) in acetonitrile in the presence of the proton scavenger 1,2,2,6,6-pentamethylpiperidine to afford loxapinium chloride (II), which is finally treated with TFA in benzene to yield the target trifluoroacetate derivative. Phosphate (IV) can be obtained from phosphite (III) by treatment with KHCO3 and KMnO4 followed by conversion to tetramethylammonium di-tert-butylphosphate by means of tetramethylammonium hydroxide and final treatment with chloroiodomethane (A) in refluxing dimethoxyethane.