FR-145715
Chemical Name: N-[3-[2-[N3-(2-Methoxyethyl)guanidino]thiazol-4-yl]benzyl]acetamide
CAS No. 149917-31-7, 149889-63-4 (monohydrochloride), 150592-79-3 (monomethanesufonate salt)
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:3-Acetylbenzonitrile (I) was protected as the ethylene ketal (II) employing ethylene glycol and boron trifluoride etherate.Reduction of the cyano group of (II) with LiAlH4 gave amine (III),and further ketal hydrolysis provided 3-acetylbenzylamine (IV).This was acetylated using acetyl chloride and Et3N to yield the intermediate amide (V).Alternatively,intermediate (V) was obtained by addition of methylmagnesium bromide to N-(3-cyanobenzyl)acetamide (VI).Bromination of (V) in dioxan furnished the bromoacetophenone (VII).This was cyclized to the aminothiazole (IX) by treatment with thiourea (VIII) in refluxing ethanol.Condensation of (IX) with benzoyl isothiocyanate (X) provided the benzoyl thiourea (XI).After selective hydrolysis of the benzoyl group of (XI) with NaOH in MeOH-H2O at 60 C,the resulting thiourea (XII) was methylated with iodomethane yielding S-methylisothiourea (XIII).Finally,displacement of the methylthio group with 2-methoxyetylamine (XIV) furnished the title guanidinothiazole.
合成路线:An alternative procedure consisted in the bromination of acetophenone (V),followed by formation of the target thiazole by condensation of the resulting bromoacetophenone (VII) with [(2-methoxyethylamino)(amino)methylene]thiourea (XV).
📌 参考资料/链接：
参考文献标题:Guanidino thiazoles and their use as H2-receptor antagonist
文献作者:Katsura,Y.; Tomishi,T.; Inoue,Y.; Takasugi,H.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0545376; JP 1994321921; US 5532258
📄 详细内容
合成路线:3-Acetylbenzonitrile (I) was protected as the ethylene ketal (II) employing ethylene glycol and boron trifluoride etherate.Reduction of the cyano group of (II) with LiAlH4 gave amine (III),and further ketal hydrolysis provided 3-acetylbenzylamine (IV).This was acetylated using acetyl chloride and Et3N to yield the intermediate amide (V).Alternatively,intermediate (V) was obtained by addition of methylmagnesium bromide to N-(3-cyanobenzyl)acetamide (VI).Bromination of (V) in dioxan furnished the bromoacetophenone (VII).This was cyclized to the aminothiazole (IX) by treatment with thiourea (VIII) in refluxing ethanol.Condensation of (IX) with benzoyl isothiocyanate (X) provided the benzoyl thiourea (XI).After selective hydrolysis of the benzoyl group of (XI) with NaOH in MeOH-H2O at 60 C,the resulting thiourea (XII) was methylated with iodomethane yielding S-methylisothiourea (XIII).Finally,displacement of the methylthio group with 2-methoxyetylamine (XIV) furnished the title guanidinothiazole.
合成路线:An alternative procedure consisted in the bromination of acetophenone (V),followed by formation of the target thiazole by condensation of the resulting bromoacetophenone (VII) with [(2-methoxyethylamino)(amino)methylene]thiourea (XV).
参考文献标题:Anti-Helicobacter pylori agents.4.2-(Substituted guanidino)-4-phenylthiazoles and some structurally rigid derivatives
文献作者:Katsura,Y.; Tomishi,T.; Inoue,Y.; Sakane,K.; Matsumoto,Y.; Morinaga,C.; Ishikawa,H.; Takasugi,H.
参考来源:J Med Chem 2000,43(17),3315
产品链接: CAS No. 149917-31-7››