Sivelestat sodium hydrate, EI-546, Ono-5046.Na, Elaspol
西维来司他 Chemical Name: N-[2-[4-(tert-Butoxycarbonyloxy)phenylsulfonamido]benzoyl]glycine sodium salt tetrahydrate
CAS No. 201677-61-4, 127373-66-4 (anhydrous, free acid), 150374-95-1 (monoNa salt)
项目整合开发状态: Launched-2002
项目研究机构: Ono (Originator), Lilly (Licensee)
合成路线:The condensation of 4-(pivaloyloxy)benzenesulfonyl chloride (I) with the glycine benzyl ester (II) in pyridine gives N-[2-[4-(pivaloyloxy)phenylsulfonamido]benzoyl]glycine benzyl ester (III),which is then debenzylated by hydrogenolysis with H2 over Pd/C in methanol.The starting compounds (I) and (II) are obtained as follows:1) The condensation of pivaloyl chloride (IV) with 4-hydroxybenzenesulfonic acid (V) by means of NaOH in THF - water gives 4-(pivaloyloxy)benzenesulfonic acid (VI),which is then treated with SOCl2 to afford the corresponding acyl chloride (I).2) The condensation of 2-nitrobenzoyl chloride (VII) with glycine benzyl ester (VIII) by means of triethylamine in dichloromethane gives N-(2-nitrobenzoyl)glycine benzyl ester (IX),which is then reduced with Fe - HCl in THF - water to the amino derivative (II).
📌 参考资料/链接：
参考文献标题:Derivs.of p-substituted phenyl ester of pivalic acid
文献作者:Imaki,K.; Arai,Y.; Okegawa,T.(Ono Pharmaceutical Co.,Ltd.)
参考来源:EP 0347168; JP 1991020253; JP 1994179645; US 5017610; US 5336681; US 5403850
📄 详细内容
合成路线:The condensation of 4-(pivaloyloxy)benzenesulfonyl chloride (I) with the glycine benzyl ester (II) in pyridine gives N-[2-[4-(pivaloyloxy)phenylsulfonamido]benzoyl]glycine benzyl ester (III),which is then debenzylated by hydrogenolysis with H2 over Pd/C in methanol.The starting compounds (I) and (II) are obtained as follows:1) The condensation of pivaloyl chloride (IV) with 4-hydroxybenzenesulfonic acid (V) by means of NaOH in THF - water gives 4-(pivaloyloxy)benzenesulfonic acid (VI),which is then treated with SOCl2 to afford the corresponding acyl chloride (I).2) The condensation of 2-nitrobenzoyl chloride (VII) with glycine benzyl ester (VIII) by means of triethylamine in dichloromethane gives N-(2-nitrobenzoyl)glycine benzyl ester (IX),which is then reduced with Fe - HCl in THF - water to the amino derivative (II).
参考文献标题:Glycine deriv.monosodium salt tetrahydrate having an inhibitory effect on elastase
文献作者:Imaki,K.; Wakatsuka,H.(Ono Pharmaceutical Co.,Ltd.)
参考来源:EP 0539223; JP 1993194366
合成路线:The condensation of 4-(pivaloyloxy)benzenesulfonyl chloride (I) with the glycine benzyl ester (II) in pyridine gives N-[2-[4-(pivaloyloxy)phenylsulfonamido]benzoyl]glycine benzyl ester (III),which is then debenzylated by hydrogenolysis with H2 over Pd/C in methanol.The starting compounds (I) and (II) are obtained as follows:1) The condensation of pivaloyl chloride (IV) with 4-hydroxybenzenesulfonic acid (V) by means of NaOH in THF - water gives 4-(pivaloyloxy)benzenesulfonic acid (VI),which is then treated with SOCl2 to afford the corresponding acyl chloride (I).2) The condensation of 2-nitrobenzoyl chloride (VII) with glycine benzyl ester (VIII) by means of triethylamine in dichloromethane gives N-(2-nitrobenzoyl)glycine benzyl ester (IX),which is then reduced with Fe - HCl in THF - water to the amino derivative (II).
参考文献标题:Ono-5046
文献作者:Castar,J.; Graul,A.; Prous,J.
参考来源:Drugs Fut 1994,19(11),1000
产品链接: CAS No. 201677-61-4›› 产品链接: CAS No.127373-66-4››