新产品编号:519405
Chemical Name: N-[4-(3-Bromophenylamino)quinazolin-6-yl]-4-(dimethylamino)-2(E)-butenamide
CAS No. 220699-51-4
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:5-Nitroanthranilonitrile (I) was converted into the corresponding formamidine (II) using dimethylformamide dimethyl acetal.Heating a solution of formamidine (II) and 3-bromoaniline (III) in HOAc gave the nitro quinazoline (IV).The nitro group of (IV) was then reduced with iron in HOAc to yield the intermediate amino quinazoline (V).
合成路线:Methyl 4-bromocrotonate (VI) was hydrolyzed with barium hydroxide under controlled conditions and the resulting bromocrotonic acid (VII) was converted to the corresponding acid chloride (VIII) by treatment with oxalyl chloride.Condensation of acid chloride (VIII) with amino quinazoline (V) produced the bromocrotonamide (IX).Finally,nucleophilic displacement of the allylic bromine with dimethylamine provided the title compound.
📌 参考资料/链接：
参考文献标题:Substd.quinazoline derivs.and their use as tyrosine kinase inhibitors
文献作者:Wissner,A.; Johnson,B.D.; Zhang,N.; Tsou,H.-R.; Hamann,P.R.(American Cyanamid Co.)
参考来源:EP 1000039; JP 2001515071; WO 9909016
📄 详细内容
合成路线:5-Nitroanthranilonitrile (I) was converted into the corresponding formamidine (II) using dimethylformamide dimethyl acetal.Heating a solution of formamidine (II) and 3-bromoaniline (III) in HOAc gave the nitro quinazoline (IV).The nitro group of (IV) was then reduced with iron in HOAc to yield the intermediate amino quinazoline (V).
合成路线:Methyl 4-bromocrotonate (VI) was hydrolyzed with barium hydroxide under controlled conditions and the resulting bromocrotonic acid (VII) was converted to the corresponding acid chloride (VIII) by treatment with oxalyl chloride.Condensation of acid chloride (VIII) with amino quinazoline (V) produced the bromocrotonamide (IX).Finally,nucleophilic displacement of the allylic bromine with dimethylamine provided the title compound.
参考文献标题:6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity
文献作者:Tsou,H.-R.; Mamuya,N.; Johnson,B.D.; Reich,M.F.; Gruber,B.C.; Ye,F.; Nilakantan,R.; Shen,R.; Discafani,C.; DeBlanc,R.; Davis,R.; Koehn,F.E.; Greenberger,L.M.; Wang,Y.F.; Wissner,A.
参考来源:J Med Chem 2001,44(17),2719