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    • 2. 发明公开
    • 결정성 세포조프란 중간체의 제조방법
    • 制备晶体中间体的方法
    • KR1020090109256A
    • 2009-10-20
    • KR1020080034609
    • 2008-04-15
    • 주식회사 엔지켐생명과학
    • 이태석육진수이종수유창현이주철이철민김은경이완희
    • C07D501/02C07D487/04C07D403/02
    • Y02P20/55C07D501/18
    • PURPOSE: A method for producing a crystalline Cefozopran intermediate is provided to produce useful Cefozopran as antibiotics with high purity and high yield. CONSTITUTION: A method for producing a crystalline Cefozopran intermediate comprises: a step of reacting 7-aminocephalosporanic acid with acylating agent; a step of synthesizing a cephalosporanic acid derivative which amine group of site 7 is protected; a step of reacting cephalosporanic acid derivative with imidazo-[1,2-b]pyridazine; a step of synthesizing 7 beta-acylamino-3-[(imidazo-[1,2-b]pyridazinium-1-yl)methyl]-3-cephem-5-carboxylate; a step of removing amine group protection group; and a step of synthesizing 7 beta-acylamino-3-[(imidazo-[1,2-b]pyridazinium-1-yl)methyl]-3-cephem-5-carboxylate hydrochloride.
    • 目的:提供一种生产结晶Cefozopran中间体的方法,以生产有效的Cefozopran作为高纯度和高产率的抗生素。 构成:结晶Cefozopran中间体的制备方法包括:使7-氨基头孢烷酸与酰化剂反应的步骤; 合成位点7的胺基保护的头孢菌酸衍生物的工序; 使头孢菌酸衍生物与咪唑并[1,2-b]哒嗪反应的步骤; 合成7β-酰氨基-3 - [(咪唑并[1,2-b]哒嗪鎓-1-基)甲基] -3-头孢烯-5-羧酸酯的步骤; 去除胺基保护基的一个步骤; 和合成7β-酰基氨基-3 - [(咪唑并[1,2-b]哒嗪鎓-1-基)甲基] -3-头孢烯-5-羧酸酯盐酸盐的步骤。
    • 5. 发明公开
    • (1­옥사­또는 1­티아­)3­세펨 유도체의 제조 방법
    • (1-氧化物或1-THIA-)3-CEPHEM衍生物的制备
    • KR1020080111062A
    • 2008-12-22
    • KR1020087025168
    • 2007-03-14
    • 카르테시아 에스.에이.에스. 디 엠마누엘라 미글리아바카 앤 씨.
    • 달’아스타,레오네
    • C07D501/04C07D505/06C07D505/16
    • C07D501/02C07D501/18C07D503/02C07D503/10
    • There is described a process for the preparation of carboxy-protected 7beta-amino-7alpha-methoxy-(l-oxa-or l-thia-)3-(l-substituted-lH-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid. Said process comprises (a) reacting a carboxy-protected 7-amino-3-chloromethyl-(l-oxa-or 1-thia-) 3-cephem-4-carboxylate with an alkyl-or aryl-sulfenyl chloride; (b) reacting the corresponding 7-alkyl-or aryl-thioimino derivative with a l-(alkyl-o i-hydroxyalkyl-)lH-tetrazol-5-ylthiol; and (c) reacting the corresponding 7-(alkyl-or aryl-)thioimino-3-(l-substituted-lH-tetrazol-5-yl)Momethyl-(1-oxa-or l-thia-)3-cephem with methanol in the presence of triphenylphosphine and aluminum chloride neutralized with a base. The reaction of the obtained carboxy-protected 7beta-amino-7alpha-methoxy-(1-oxa-or 1-thia-)3-(1-substituted-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid with activated 2-(cyanomethylthio)acetic or 2-(difiuoromethyl thio)acetic acid affords, after final removal of the protecting ester group, cefmetazole and fiomoxef, respectively. The 7-(alkyl-or aryl)thioimino-3-(1-substituted-1H-tetrazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem intermediates are new compounds. ® KIPO & WIPO 2009
    • 描述了制备羧基保护的7β-氨基-7α-甲氧基 - (1-氧杂 - 或1-硫杂 - )3-(1-取代-1H-四唑-5-基)硫代甲基-3- 头孢烯-4-羧酸。 所述方法包括(a)使羧基保护的7-氨基-3-氯甲基 - (1-氧杂 - 或1-硫杂)-3-头孢烯-4-羧酸酯与烷基 - 或芳基 - 亚硫酰氯反应; (b)使相应的7-烷基 - 或芳基 - 硫代亚氨基衍生物与1-(烷基 - 邻 - 羟基烷基)-1H-四唑-5-基硫醇反应; 和(c)使相应的7-(烷基 - 或芳基)硫代亚氨基-3-(1-取代-1H-四唑-5-基)甲基 - (1-氧杂 - 或1-硫杂 - )-3-头孢烯与 在三苯基膦和氯化铝存在下用碱中和的甲醇。 得到的羧基保护的7-氨基-7α-甲氧基 - (1-氧杂 - 或1-硫杂 - )3-(1-取代-1H-四唑-5-基)硫甲基-3-头孢-4-酮 羧酸与活化的2-(氰基甲硫基)乙酸或2-(二氟甲硫基)乙酸分别得到最终去除保护酯基,头孢美唑和肟基。 7-(烷基 - 或芳基)硫代亚氨基-3-(1-取代-1H-四唑-5-基)硫甲基-1-脱硫-1-氧杂-3-甲氧基中间体是新的化合物。 ®KIPO&WIPO 2009