公开(公告)号：EP2643304A2

公开(公告)日：2013-10-02

申请号：EP11843289.7

申请日：2011-11-23

申请人： Sequent Scientific Ltd. ,  Arulmoli, Thangavel

发明人： RANE, Ramkrishna Appaji ,  NAITHANI, Sushil ,  NATIKAR, Rajendra Devendra ,  VERMA, Sudhakar

IPC分类号： C07D235/30

CPC分类号： C07D235/32 ,  C07D235/30

摘要： The present invention discloses a novel, cost-effective process for preparation of a benzimidazole carbamates compound. Specifically, it relates to the process for the preparation of anti-parasite bulk drug albendazole. The process comprises a) thiocyanating 2-nitroaniline of formula VI with ammonium thiocyanated in presence of a halogen to obtain 2-nitro-4-thiocyanoaniline of formula V; b)propylating 2-nitro-4-thiocyanoaniline of formula V with propylbromide in presence of n-propanol and a base in absence of a phase transfer catalyst to obtain 4-propylthio-2-nitroaniline of formula III; C) reducing the nitro group of 4- propylthio-2-nitroaniline prepared in step b) by reacting an aqueous alkali metal sulphide or an alkaline metal sulphide to obtain 4-propylthio-o-phenylenediamine of formula II; and d)condensing 4-propylthio-o-phenylenediamine of formula II with alkali or alkaline earth metal salt of methylcyano carbamate in presence of an acid to form Albendazole of formula I.

摘要翻译： 本发明公开了一种制备苯并咪唑氨基甲酸酯化合物的新型成本有效的方法。 具体而言，涉及制备抗寄生虫药物阿苯达唑的方法。 该方法包括a）在卤素存在下硫氰酸化式VI的2-硝基苯胺与硫氰酸铵反应，得到式Ⅴ的2-硝基-4-硫代氰胺; b）在不存在相转移催化剂的情况下，在正丙醇和碱的存在下，用丙基溴将式V的2-硝基-4-氰基氰胺丙基化，得到式III的4-丙硫基-2-硝基苯胺; C）通过使碱金属硫化物水溶液或碱金属硫化物水溶液还原步骤b）中制备的4-丙基硫代-2-硝基苯胺的硝基，得到式II的4-丙硫基 - 邻苯二胺; 和d）将式II的4-丙硫基 - 邻苯二胺与甲基氰基氨基甲酸酯的碱金属或碱土金属盐在酸存在下缩合形成式I的阿苯达唑。

公开(公告)号：EP2642995A2

公开(公告)日：2013-10-02

申请号：EP11843342.4

申请日：2011-11-23

申请人： Sequent Scientific Ltd.

发明人： RANE, Ramkrishna Appaji ,  VERMA, Sudhakar ,  ARULMOLI, Thangavel

IPC分类号： A61K31/4184 ,  C07C43/00

CPC分类号： C07D235/28

摘要： The present invention discloses a method for preparing Triclabendazole comprising condensing N-(4,5-dichloro-2-nitrophenyl)acetamide with 2,3-dichlorophenol to obtain 4-chloro-5(2,3-dichlorophenoxy)-2-nitrophenyl acetamide and it to obtain 4- chloro-5(2,3-dichlorophenoxy)-2-nitroaniline; reducing 4-chloro-5(2,3- dichlorophenoxy)-2-nitroaniline in presence of Raney nickel to obtain 4-chloro-5- (2,3-dichlorophenoxy)benzene-l,2-diamine of; cyclising 4-chloro-5-(2,3- dichlorophenoxy)benzene-l,2-diamine in presence of carbondisulfide to obtain 6- chloro-5-(2,3-dichlorophenoxy)-lH-benzimidazole-2-thiol; methylating 6-chloro-5- (2,3-dichlorophenoxy)-lH-benzimidazole-2 -thiol using a methylating agent to obtain triclabendazole methanesulfonate salt; converting triclabendazole methanesulfonate salt to hydrochloride salt of Triclabendazole and hydrolysing it to obtain Triclabendazole.

摘要翻译： 本发明公开了一种三氯苯达唑的制备方法，其包括将N-（4,5-二氯-2-硝基苯基）乙酰胺与2,3-二氯苯酚缩合得到4-氯-5（2,3-二氯苯氧基）-2- 硝基苯基乙酰胺，得到4-氯-5（2,3-二氯苯氧基）-2-硝基苯胺; 在阮内镍存在下还原4-氯-5（2,3-二氯苯氧基）-2-硝基苯胺，得到4-氯-5-（2,3-二氯苯氧基）苯-1,2-二胺， 在二硫化碳存在下环化4-氯-5-（2,3-二氯苯氧基）苯-1,2-二胺，得到6-氯-5-（2,3-二氯苯氧基）-1H-苯并咪唑-2-硫醇; 使用甲基化剂甲基化6-氯-5-（2,3-二氯苯氧基）-1H-苯并咪唑-2-硫醇，得到三氯苯达唑甲磺酸盐; 将三氯苯达唑甲磺酸盐转化为三氯苯达唑的盐酸盐并水解，得到三氯苯达唑。