KW-3635
Chemical Name: (E)-11-[2-(5,6-Dimethyl-1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepine-2-carboxylic acid sodium salt monohydrate
CAS No. 127166-41-0 (anhydrous), 127166-39-6 (anhydrous free acid), 127166-40-9 (anhydrous free acid monoHCl salt)
项目整合开发状态: Phase I
项目研究机构: Kyowa Hakko (Originator)
合成路线:The reaction of 11-methylene-6,11-dihydrodibenzo[b,e]oxepine-2-carboxylic acid methyl ester (I) with N-methylpiperazine and paraformaldehyde by means of trifluoroacetic acid in hot tetrachloroethane gives 11-[2-(4-methylpiperazin-1-yl)ethylidene]-6,11-dihydrodibenzo[b,e]oxepine-2-carboxylic acid methyl ester (II),which by reaction with ethyl chloroformate and sodium acetate in dichloromethane yields the corresponding 2-chloroethylidene derivative (III).The condensation of (III) with 5,6-dimethyl-1H-benzimidazole (IV) in refluxing toluene affords the methyl ester (V) of the desired product,which is finally hydrolyzed with sodium methoxide in methanol.
📌 参考资料/链接：
参考文献标题:Tricyclic cpds
文献作者:Oshima,E.; Obase,H.; Karasawa,A.; Kubo,K.; Miki,I.; Ishii,A.(Kyowa Hakko Kogyo Co.,Ltd.)
参考来源:EP 0345747; JP 1990091040; US 4999363; US 5118701; US 5242931; US 5302596
📄 详细内容
合成路线:The reaction of 11-methylene-6,11-dihydrodibenzo[b,e]oxepine-2-carboxylic acid methyl ester (I) with N-methylpiperazine and paraformaldehyde by means of trifluoroacetic acid in hot tetrachloroethane gives 11-[2-(4-methylpiperazin-1-yl)ethylidene]-6,11-dihydrodibenzo[b,e]oxepine-2-carboxylic acid methyl ester (II),which by reaction with ethyl chloroformate and sodium acetate in dichloromethane yields the corresponding 2-chloroethylidene derivative (III).The condensation of (III) with 5,6-dimethyl-1H-benzimidazole (IV) in refluxing toluene affords the methyl ester (V) of the desired product,which is finally hydrolyzed with sodium methoxide in methanol.
参考文献标题:Synthesis and biological activity of a novel thromboxane A2 receptor antagonist,KW-3635,and its related derivatives
文献作者:Ishii,A.; Higo,K.; Miki,I.; Kubo,K.; Ohshima,E.; Takami,H.; Karasawa,A.; Sato,H.; Obase,H.; Shirakura,S.
参考来源:11th Symp Med Chem (Dec 4-5,Tokushima) 1990,Abst P-6
合成路线:The reaction of 11-methylene-6,11-dihydrodibenzo[b,e]oxepine-2-carboxylic acid methyl ester (I) with N-methylpiperazine and paraformaldehyde by means of trifluoroacetic acid in hot tetrachloroethane gives 11-[2-(4-methylpiperazin-1-yl)ethylidene]-6,11-dihydrodibenzo[b,e]oxepine-2-carboxylic acid methyl ester (II),which by reaction with ethyl chloroformate and sodium acetate in dichloromethane yields the corresponding 2-chloroethylidene derivative (III).The condensation of (III) with 5,6-dimethyl-1H-benzimidazole (IV) in refluxing toluene affords the methyl ester (V) of the desired product,which is finally hydrolyzed with sodium methoxide in methanol.
参考文献标题:KW-3635
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1992,17(9),782
产品链接: CAS No.127166-39-6››