NSL-96184
Chemical Name: 1-[3-[2-Fluoro-4-(thiazolidin-3-ylcarboimidoyl)benzamido]-2,2-dimethylpentanoyl]piperidine-4-acetic acid ethyl ester
CAS No. 200490-65-9
项目整合开发状态: Preclinical
项目研究机构: Nippon Steel (Originator)
合成路线:Protection of beta-alanine derivative (I) with di-tert-butyl dicarbonate afforded the tert-butyl carbamate (II).This was condensed with ethyl piperidine-4-acetate (III) using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyuronium hexafluorophosphate (HATU) and diisopropyl ethylamine to give amide (IV).Subsequent Boc deprotection of (IV) with trifluoroacetic acid provided amine (V),which was coupled with 2-fluoro-4-cyanobenzoic acid (VI) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole yielding (VII).Treatment of the resulting cyanobenzamide (VII) with SH2 and Et3N produced the corresponding thioamide,which was S-alkylated with MeI to give (VIII).Finally,displacement of the methylthio group of (VIII) with thiazolidine (IX) furnished the corresponding amidine.
📌 参考资料/链接：
参考文献标题:Fibrinogen receptor antagonists and medicinal preparations containing the same as the active ingredient
文献作者:Hayashi,Y.; Harada,T.; Tachiki,A.; Katada,J.(Nippon Steel Corp.)
参考来源:EP 0852225; JP 1998017550; WO 9749682
📄 详细内容
合成路线:Protection of beta-alanine derivative (I) with di-tert-butyl dicarbonate afforded the tert-butyl carbamate (II).This was condensed with ethyl piperidine-4-acetate (III) using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyuronium hexafluorophosphate (HATU) and diisopropyl ethylamine to give amide (IV).Subsequent Boc deprotection of (IV) with trifluoroacetic acid provided amine (V),which was coupled with 2-fluoro-4-cyanobenzoic acid (VI) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole yielding (VII).Treatment of the resulting cyanobenzamide (VII) with SH2 and Et3N produced the corresponding thioamide,which was S-alkylated with MeI to give (VIII).Finally,displacement of the methylthio group of (VIII) with thiazolidine (IX) furnished the corresponding amidine.
参考文献标题:GPIIb/IIIa integrin antagonists with the new conformational restriction unit,trisubstituted beta-amino acid derivatives,and substituted benzamidine structure
文献作者:Hayashi,Y.; Katada,J.; Harada,T.; Tachiki,A.; Iijima,K.; Takiguchi,Y.; Muramatsu,M.; Miyazaki,H.; Asari,T.; Okazaki,T.; Sato,Y.; Yasuda,E.; Yano,M.; Uno,I.; Ojima,I.
参考来源:J Med Chem 1998,41(12),2345