DA-3934
Chemical Name: 2-[3-[3-[N-[2-(N-Methyl-N-phenylcarbamoylmethoxy)phenyl]-N-(N-methyl-N-phenylcarbamoylmethyl)carbamoylmethyl]ureido]phenyl]acetic acid
CAS No. 183176-50-3
项目整合开发状态: Preclinical
项目研究机构: Daiichi Pharmaceutical (Originator)
合成路线:Coupling of 2-benzyloxyaniline (I) with N-Boc-glycine (II) by means of EDC aforded amide (III).Subsequent N-alkylation of (III) with N-methyl-N-phenyl-2-bromoacetamide (IV) in the presence of NaH provided diamide (V).Hydrogenolysis of the benzyl ether of (V) over Pd/C gave phenol derivative (VI) (1).Phenol (VI) was then alkylated with bromoamide (IV) to furnish ether (VII).After cleavage of the Boc group of (VII) with trifluoroacetic acid,the resulting amine (VIII) was reacted with carbonyldiimidazole to produce imidazolide (IX),which was subsequently coupled with aniline (X) yielding urea (XI).Finally,basic hydrolysis of the methyl ester group of (XI) gave the title carboxylic acid.
📌 参考资料/链接：
参考文献标题:Aminophenol derivs.
文献作者:Yokohama,S.; Kawagoe,K.; Takeda,Y.; Yokomizo,Y.; Yokomizo,A.(Daiichi Pharmaceutical Co.,Ltd.)
参考来源:EP 0985660; US 5919824; WO 9628416
📄 详细内容
合成路线:Coupling of 2-benzyloxyaniline (I) with N-Boc-glycine (II) by means of EDC aforded amide (III).Subsequent N-alkylation of (III) with N-methyl-N-phenyl-2-bromoacetamide (IV) in the presence of NaH provided diamide (V).Hydrogenolysis of the benzyl ether of (V) over Pd/C gave phenol derivative (VI) (1).Phenol (VI) was then alkylated with bromoamide (IV) to furnish ether (VII).After cleavage of the Boc group of (VII) with trifluoroacetic acid,the resulting amine (VIII) was reacted with carbonyldiimidazole to produce imidazolide (IX),which was subsequently coupled with aniline (X) yielding urea (XI).Finally,basic hydrolysis of the methyl ester group of (XI) gave the title carboxylic acid.
参考文献标题:Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors.II
文献作者:Takeda,Y.; Kawagoe,K.; Yokomizo,A.; Yokomizo,Y.; Hosokami,T.; Shimoto,Y.; Tabuchi,Y.; Ogihara,Y.; Otsubo,R.; Honda,Y.; Yokohama,S.
参考来源:Chem Pharm Bull 1998,46(6),951