合成路线:3-Hydroxy-4-nitrobenzaldehyde (I) was treated with 1,3-propanediol (II) in the presence of p-toluenesulfonic acid to afford the corresponding acetal (III).Catalytic hydrogenation of the nitro group of (III) over Raney-Ni gave aniline (IV),which was then acylated with chloroacetyl chloride (V) in the presence of NaHCO3 to the chloroacetamide (VI).The acetal function of (VI) was hydrolyzed with HCl in aqueous MeOH,and subsequent cyclization of the chloroacetamide (VII) using K2CO3 in acetonitrile produced the formylbenzoxazinone (VIII).The target compound was then prepared by reductive condensation of aldehyde (VIII) with N-(4-chlorophenyl)piperazine (IX) in the presence of sodium triacetoxyborohydride and AcOH.
合成路线:The reduction of 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbaldehyde (I) with NaBH4 in methanol gives the corresponding carbinol (II),which is acylated with TsCl in pyridine yielding the tosylate (III).Finally,this compound is condensed with 1-(4-chlorophenyl)piperazine (IV) by means of K2CO3 in refluxing acetonitrile.
参考文献标题:A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: Discovery of a potential atypical antipsychotic agent
文献作者:Belliotti,T.R.; Wustrow,D.J.; Brink,W.A.; Zoski,K.T.; Shih,Y.H.; Whetzel,S.Z.; Georgic,L.M.; Corbin,A.E.; Akunne,H.C.; Heffner,T.G.; Pugsley,T.A.; Wise,L.D.
参考来源:J Med Chem 1999,42(25),5181
产品链接: CAS No. 200195-01-3››