Minopafant, E-5880
Chemical Name: 1-Ethyl-2-[N-(2-methoxybenzoyl)-N-[2(R)-methoxy-3-[4-(octadecylcarbamoyloxy)piperidinocarbonyloxy]propyloxycarbonyl]aminomethyl]pyridinium chloride
CAS No. 128420-61-1
项目整合开发状态: Phase II
项目研究机构: Eisai (Originator)
合成路线:The racemic form of E-5880 is prepared as follows:The esterification of 2-methoxy-1,3-propanediol (I) with phenyl chlorocarbonate (II) in pyridine gives the diester (III),which is treated with 2-(aminomethyl)pyridine (IV) in refluxing chloroform,yielding the carbamate (V).The reaction of (V) with 4-hydroxypiperidine (VI) in refluxing chloroform affords the dicarbamate (VII),which by treatment with octadecyl isocyanate (VIII) gives the tricarbamate (X).Alternatively,(X) can be obtained by treatment of (VIII) with carbonate (II),yielding the intermediate (IX),which by treatment with octadecylamine (XI) at 100 C affords (X).The acylation of (X) with 2-methoxybenzoyl chloride (XII) in pyridine gives the precursor (XIII),which is finally treated with ethyl iodide in excess at reflux temperature and submitted to an ion exchange resin (Amberlite IRA-410 Cl- type).The optically active (R)-enantiomer is synthesized starting from L-mannitol.
📌 参考资料/链接：
参考文献标题:Glycerin deriv.and its pharmacological use
文献作者:Okano,K.; Asano,O.; Shimomura,N.; Kawahara,T.; Abe,S.; Miyazawa,S.; Miyamoto,M.; Yoshimura,H.; Harada,K.; Nagaoka,J.; Kawata,T.; Yoshimura,T.; Suzuki,H.; Souda,S.; Machida,Y.; Katayama,K.; Yamatsu,I.(Eisai Co.,Ltd.)
参考来源:AU 8937213; EP 0353474; JP 1990131467; JP 1996231508; US 5037827; US 5273985; US 5476863; US 5476864
📄 详细内容
合成路线:The racemic form of E-5880 is prepared as follows:The esterification of 2-methoxy-1,3-propanediol (I) with phenyl chlorocarbonate (II) in pyridine gives the diester (III),which is treated with 2-(aminomethyl)pyridine (IV) in refluxing chloroform,yielding the carbamate (V).The reaction of (V) with 4-hydroxypiperidine (VI) in refluxing chloroform affords the dicarbamate (VII),which by treatment with octadecyl isocyanate (VIII) gives the tricarbamate (X).Alternatively,(X) can be obtained by treatment of (VIII) with carbonate (II),yielding the intermediate (IX),which by treatment with octadecylamine (XI) at 100 C affords (X).The acylation of (X) with 2-methoxybenzoyl chloride (XII) in pyridine gives the precursor (XIII),which is finally treated with ethyl iodide in excess at reflux temperature and submitted to an ion exchange resin (Amberlite IRA-410 Cl- type).The optically active (R)-enantiomer is synthesized starting from L-mannitol.
参考文献标题:Okano,K.,Asano,O.,Shimomura,N.et al.Structure-activity relationships of platelet activating factor (PAF) antagonists
文献作者:Okano,K.; Shimomura,N.; Asano,O.; et al.
参考来源:198th ACS Natl Meet (Sept 10-15,Miami Beach) 1989,Abst MEDI 55
合成路线:The racemic form of E-5880 is prepared as follows:The esterification of 2-methoxy-1,3-propanediol (I) with phenyl chlorocarbonate (II) in pyridine gives the diester (III),which is treated with 2-(aminomethyl)pyridine (IV) in refluxing chloroform,yielding the carbamate (V).The reaction of (V) with 4-hydroxypiperidine (VI) in refluxing chloroform affords the dicarbamate (VII),which by treatment with octadecyl isocyanate (VIII) gives the tricarbamate (X).Alternatively,(X) can be obtained by treatment of (VIII) with carbonate (II),yielding the intermediate (IX),which by treatment with octadecylamine (XI) at 100 C affords (X).The acylation of (X) with 2-methoxybenzoyl chloride (XII) in pyridine gives the precursor (XIII),which is finally treated with ethyl iodide in excess at reflux temperature and submitted to an ion exchange resin (Amberlite IRA-410 Cl- type).The optically active (R)-enantiomer is synthesized starting from L-mannitol.
参考文献标题:E-5880
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1992,17(12),1082
产品链接: CAS No. 128420-61-1››