CRL-8256
Chemical Name: 5,7-Dimethoxy-3-(4-methoxyphenyl)-1-[2-(1H-tetrazol-5-yl)ethyl]quinolin-2(1H)-one
CAS No. 256424-07-4
项目整合开发状态: Preclinical
项目研究机构: Lafon (Originator)
合成路线:Acylation of 3,5-dimethoxyaniline (I) with 4-methoxyphenylacetyl chloride (II) afforded amide (III).Treatment of (III) with Vilsmeier reagent gave rise to 2-chloroquinoline derivative (IV),which was hydrolyzed to quinolinone (V) using aqueous HOAc.Conjugate addition to (V) of acrylonitrile (VI) produced the cyanoethyl quinolinone (VII).The title tetrazole was then obtained by reaction of nitrile (VII) with tributyltin azide in hot toluene.
📌 参考资料/链接：
参考文献标题:Pharmaceutical compsns.comprising 2-quinolones
文献作者:Guillaumet,G.; Darro,F.; Frydman,A.; Joseph,B.; Kiss,R.(Laboratoires L.Lafon)
参考来源:EP 1097138; FR 2781218; WO 0003990
📄 详细内容
合成路线:The cyclization of 3,5-dimethoxyaniline (I) with 2-formyl-2-(4-methoxyphenyl)acetic acid ethyl ester (II) by means of polyphosphoric acid trimethylsilyl ester (PPSE) by heating at 110 C gives the quinolone (III),which is alkylated with vinyl cyanide (IV) by means of Triton B in DMF to yield the propionitrile derivative (V).Finally,the cyano group of (V) is converted into the target tetrazolyl derivative by cyclization with tri-tert-butylstannyl azide in refluxing toluene.
参考文献标题:3-Aryl-2-quinolone derivatives: Synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration
文献作者:Joseph,B.; Darro,F.; Behard,A.; Lesur,B.; Collignon,F.; Decaestecker,C.; Frydman,A.; Guillaumet,G.; Kiss,R.
参考来源:J Med Chem 2002,45(12),2543