新产品编号:831059

Chemical Name: 4-(2,4-Dichlorophenylamino)-6-methoxy-7-[3-(4-morpholinyl)propoxy]quinoline-3-carbonitrile
CAS No. 331662-69-2
项目整合开发状态: Biological Testing
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Chloroquinoline derivative (I) was condensed with 2,4-dichloroaniline (II) in boiling ethoxyethanol in the presence of pyridine hydrochloride to furnish the title compound.

合成路线:In an alternative synthesis,the chloropropoxy derivative (III) was similarly condensed with 2,4-dichloroaniline (II) to give (IV),which was then treated with morpholine (V),yielding the title compound.

合成路线:Alkylation of 4-hydroxy-5-methoxy benzoic acid methyl ester (I) with 3-chloropropyl p-toluene sulfonate (III) by means of K2CO3 and methyl-tricapryl ammonium chloride (Aliquat 128) in refluxing acetone affords compound (III),which is then nitrated by means of HNO3 in HOAc to furnish 2-nitro derivative (IV).Reduction of the nitro moiety of (IV) by means of Fe in H2O/MeOH in the presence of ammonium chloride yields 2-amino compound (V),which is subjected to reaction with refluxing dimethylformamide dimethylacetal (VI) to provide amidine (VII).Condensation of (VII) with acetonitrile by means of n-BuLi in hexane/THF/HOAc gives substituted quinoline-carbonitrile (IX),whose hydroxyl group is replaced by a chlorine by treatment of (IX) with refluxing POCl3 to afford compound (X).Coupling of (X) with 2,4-dichloro-5-methoxyaniline (XI) in 2-ethoxyethanol in the presence of pyridine hydrochloride yields compound (XII),which is finally converted into the desired compound by condensation with 1-methylpiperazine (XII) by means of NaI in refluxing ethylene glycol dimethyl ether.