公开(公告)号：KR1020020083568A

公开(公告)日：2002-11-04

申请号：KR1020010022944

申请日：2001-04-27

Applicant: 한국화학연구원

Inventor： 김대황 ,  정근회 ,  장해성 ,  고영관 ,  류재욱 ,  우재춘 ,  구동완 ,  김선옥 ,  황의형

IPC: C07C317/32

Abstract: PURPOSE: Provided is a method for economically synthesizing glibenclamide, with powder shape, which is used as an intermediate for synthesis of medicine useful for treatment of diabetes. CONSTITUTION: The method comprises the steps of (i) reacting N-phenethyl-5-chloro-2-methoxybenzamide with chlorosulfonic acid(ClSO3H) represented by formula 2 in the presence of thionyl chloride(SOCl2) to form p-(N-phenethyl-5-chloro-2-methoxybenzamide)sulfonylchloride represented by formula 3; (ii) reacting sulfonylchloride compound represented by formula 3 with ammonia to form p-(N-phenethyl-5-chloro-2-methoxybenzamide)sulfoneamide represented by formula 4; (iii) reacting sulfoneamide compound represented by formula with alkali metal hydroxide in the presence of alcohol solvent to form p-(N-phenethyl-5-chloro-2-methoxybenzamide)sulfone amide-metal salt represented by formula 5; and (iv) reacting the metal represented by formula 5 with cyclohexyl isocyanate or phenylcyclohexyl carbamate to form glibenclamide represented by formula 1.

Abstract translation: 目的：提供一种经济合成格列本脲的方法，其具有粉末形状，用作合成用于治疗糖尿病的药物的中间体。 方法：该方法包括以下步骤：（i）使N-苯乙基-5-氯-2-甲氧基苯甲酰胺与亚硫酰氯（SOCl 2）存在下由式2表示的氯磺酸（ClSO 3 H）反应，形成对 - （N-苯乙基 -5-氯-2-甲氧基苯甲酰胺）磺酰氯; （ii）使由式3表示的磺酰氯化合物与氨反应以形成由式4表示的对 - （N-苯乙基-5-氯-2-甲氧基苯甲酰胺）磺酰胺; （iii）在醇溶剂存在下使由式表示的磺酰胺化合物与碱金属氢氧化物反应，形成由式5表示的对 - （N-苯乙基-5-氯-2-甲氧基苯甲酰胺）砜酰胺 - 金属盐; 和（iv）使由式5表示的金属与环己基异氰酸酯或苯基环己基氨基甲酸酯反应，形成由式1表示的格列本脲。

公开(公告)号：KR100402055B1

公开(公告)日：2003-10-17

申请号：KR1020010022944

申请日：2001-04-27

Applicant: 한국화학연구원

Inventor： 김대황 ,  정근회 ,  장해성 ,  고영관 ,  류재욱 ,  우재춘 ,  구동완 ,  김선옥 ,  황의형

IPC: C07C317/32

Abstract: PURPOSE: Provided is a method for economically synthesizing glibenclamide, with powder shape, which is used as an intermediate for synthesis of medicine useful for treatment of diabetes. CONSTITUTION: The method comprises the steps of (i) reacting N-phenethyl-5-chloro-2-methoxybenzamide with chlorosulfonic acid(ClSO3H) represented by formula 2 in the presence of thionyl chloride(SOCl2) to form p-(N-phenethyl-5-chloro-2-methoxybenzamide)sulfonylchloride represented by formula 3; (ii) reacting sulfonylchloride compound represented by formula 3 with ammonia to form p-(N-phenethyl-5-chloro-2-methoxybenzamide)sulfoneamide represented by formula 4; (iii) reacting sulfoneamide compound represented by formula with alkali metal hydroxide in the presence of alcohol solvent to form p-(N-phenethyl-5-chloro-2-methoxybenzamide)sulfone amide-metal salt represented by formula 5; and (iv) reacting the metal represented by formula 5 with cyclohexyl isocyanate or phenylcyclohexyl carbamate to form glibenclamide represented by formula 1.

Abstract translation: 目的：提供一种经济地合成格列本脲粉末状的方法，其用作合成用于治疗糖尿病的药物的中间体。 构成：该方法包括以下步骤：（i）使N-苯乙基-5-氯-2-甲氧基苯甲酰胺与式2代表的氯磺酸（ClSO 3 H）在亚硫酰氯（SOCl 2）存在下反应形成对 - （N-苯乙基 -5-氯-2-甲氧基苯甲酰胺）磺酰氯，由式3表示; （ii）使由式3表示的磺酰氯化合物与氨反应以形成由式4表示的对 - （N-苯乙基-5-氯-2-甲氧基苯甲酰胺）磺酰胺; （ⅲ）在醇溶剂存在下使下式表示的磺酰胺化合物与碱金属氢氧化物反应，生成式5表示的对 - （N-苯乙基-5-氯-2-甲氧基苯甲酰胺）磺酰胺 - 金属盐; （iv）使由式5表示的金属与环己基异氰酸酯或苯基环己基氨基甲酸酯反应以形成由式1表示的格列本脲。