新产品编号:584267
Chemical Name: 2-[2,6-Dichloro-4-[2-[2(R)-hydroxy-2-(4-hydroxyphenyl)-1(S)-methylethylamino]ethyl]phenylamino]acetic acid hydrate
CAS No. 227467-90-5 (anhydrous)
项目整合开发状态: Preclinical
项目研究机构: Kissei (Originator)
合成路线:The condensation of 2-(4-aminophenyl)ethanol (I) with ethyl 2-bromoacetate (II) by means of K2CO3 in DMF gives 2-[4-(2-hydroxyethyl)phenylamino]acetic acid ethyl ester (III),which is chlorinated with t-butyl hypochlorite in dichloromethane to yield the 2,6-dichlorophenyl derivative (IV).The bromination of (IV) by means of PPh3 and CBr4 in dichloromethane affords the 2-bromoethyl derivative (V),which is condensed with (1R,2S)-2-amino-1-(4-hydroxyphenyl)-1-propanol (VI) by means of DIEA in hot DMF to provide the ethyl ester precursor (VII).Finally,this compound is hydrolyzed with aq.1N NaOH to give the target N-phenylglycine derivative.
📌 参考资料/链接：
参考文献标题:Phenylaminoalkylcarboxylic acid derivs.and medicinal compsns.containing the same
文献作者:Sato,M.; Tanaka,N.; Akahane,M.; Tamai,T.; Muranaka,H.; Mukaiyama,H.; Hirabayashi,A.(Kissei Pharmaceutical Co.,Ltd.)
参考来源:EP 1043308; WO 9931045
📄 详细内容
合成路线:The condensation of 2-(4-aminophenyl)ethanol (I) with ethyl 2-bromoacetate (II) by means of K2CO3 in DMF gives 2-[4-(2-hydroxyethyl)phenylamino]acetic acid ethyl ester (III),which is chlorinated with t-butyl hypochlorite in dichloromethane to yield the 2,6-dichlorophenyl derivative (IV).The bromination of (IV) by means of PPh3 and CBr4 in dichloromethane affords the 2-bromoethyl derivative (V),which is condensed with (1R,2S)-2-amino-1-(4-hydroxyphenyl)-1-propanol (VI) by means of DIEA in hot DMF to provide the ethyl ester precursor (VII).Finally,this compound is hydrolyzed with aq.1N NaOH to give the target N-phenylglycine derivative.
参考文献标题:Discovery of novel N-phenylglycine derivatives as potent and selective beta3-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence
文献作者:Tanaka,N.; Tamai,T.; Mukaiyama,H.; Hirabayashi,A.; Muranaka,H.; Akahane,S.; Miyata,H.; Akahane,M.
参考来源:J Med Chem 2001,44(9),1436