【药物名称】Sivelestat sodium hydrate, EI-546, Ono-5046.Na, Elaspol
化学结构式(Chemical Structure):
参考文献No.11675
标题:Derivs. of p-substituted phenyl ester of pivalic acid
作者:Imaki, K.; Arai, Y.; Okegawa, T. (Ono Pharmaceutical Co., Ltd.)
来源:EP 0347168; JP 1991020253; JP 1994179645; US 5017610; US 5336681; US 5403850
合成路线图解说明:

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No.20658
标题:Glycine deriv. monosodium salt tetrahydrate having an inhibitory effect on elastase
作者:Imaki, K.; Wakatsuka, H. (Ono Pharmaceutical Co., Ltd.)
来源:EP 0539223; JP 1993194366
合成路线图解说明:

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No.268120
标题:Ono-5046
作者:Casta馿r, J.; Graul, A.; Prous, J.
来源:Drugs Fut 1994,19(11),1000
合成路线图解说明:

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).

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