• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Compounds of the formula I <IMAGE> whose radicals are specified in Patent Claim 1, are obtained by reaction of a compound of the formula IV <IMAGE> containing radicals as in Patent Claim 1, with a compound of the formula V, Z<1>-B-Het, in which B is the group -CH2- or -CH(CH3)- and Z<1> denotes a reactive, esterified hydroxyl group or -SH. The compounds of the formula I can be used for affecting gastric acid secretion of mammals, in particular humans. They are best suited for the treatment, for example, of gastric ulcers or similar disorders.
    公开号:SU795476A3
    申请号:SU752106386
    申请日:1975-02-14
    公开日:1981-01-07
    发明作者:Бернхард Бернтссон Педер；Аке Ингемар Карльссон Стиг；Эрик Гарберг Ларс；Кристер Юнггрен Ульф；Эрик Съестранд Свен；Вика Фон Витткен Сундель Гунхильд
    申请人:Аб Хессле (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a process for the preparation of new benzimide azole derivatives, which affect the release of gastric acid and can be used for the treatment of, for example, heptic ulcer, i.e. in medicine. A method of producing 2- (pyri dilmethylthio) -benzimidazoles in which the benzene core is unsubstituted or substituted by a hydrogen atom, methyl, a nitro group or a halogen atom, by reacting 2-mercaptobenzimidazole with aminomethylpyridine or with chloromethylpyridine in a jjene, you would have to apply a procedure to obtain a solvent. The aim of the invention is to obtain benzimidazole derivatives, which expand the arsenal of human exposure agents. This goal is achieved by a method for preparing previously unknown benzimidazole derivatives of general formula I .IT. where R and R are the same or different and mean hydrogen, halogen, alkyl with up to 4 carbon atoms, carboxyl, carboalkoxy with up to 4 carbon atoms in the alkoxy group, methoxy, oxy, oxalkyl with up to 4 carbon atoms in the alkyl part and alkanoyl with up to 4 in. carbon atoms. any position; R is hydrogen, alkanoyl with up to 4 carbon atoms, carbalkoxy with up to 4 carbon atoms; A is a -SCH2- or -5CH (CH3) - group, with a sulfur atom bound to a benzimidazole group; Het is 2-pyridyl, unsubstituted or substituted by methyl and chlorine, and if R and R are hydrogen, halo, methyl, then 2, alkanoyl with up to 4 carbon atoms, or carbalkoxy with up to 4 carbon atoms and / or Het means 2 -pyridyl substituted with methyl or chlorine, and / or A means the -5CH group (CH3) or their salts, consisting in that the compounds of formula E
    where R, R, Kd have the above values, Z - SH
    or a reactive esterified hydroxyl group, reacted with a compound of the formula ffl
    z-CH-Het
    R,
    where R5 is hydrogen or methyl;
    Not have the above values, in an aqueous organic medium at a temperature of 40-19 ° C in the presence of a base, followed by isolation of the target product in free form or as a salt.

    Example 1.0.1 mol of 5-ethyl-2-mercaptobenzimidazole is dissolved in a mixture of 200 ml of water, 200 ml of ethanol and 0.2 mol of hydroxide. Then 0.1 mol of 2-chloromethylpyridine hydrochloride is added and the mixture is heated under reflux at a temperature of 78.5-80 ° C for 2 hours. The sodium chloride formed is filtered and the solution is evaporated in vacuo. The residue is dissolved in acetone and treated with activated charcoal. An equivalent amount of concentrated hydrochloric acid is then added and 2- (2-pyridylmethylthio.) - (5-ethyl) -benzimidazole monohydrochloride with m.p. . Exit 68% of theory.
    Approximately 2. 0.1 mol of 5-acetyl-4-methyl-2 mercaptobenzimidazole was dissolved in a mixture of 20 ml of water, 200 ml of propanol and 0.2 mol of hydroxide. Then, 0.1 mol of 2-chloromethyl-5-methylpyridine hydrochloride is added and the mixture is heated with a reverse chiller at a temperature of 97-100 ° C for: 2 hours. The resulting sodium chloride is filtered and the solution is evaporated in vacuo. The residue is dissolved in acetone and treated with active carbon. The solution is evaporated and the 2- 2- (5-methyl) -pyridylmethylthio1-5-acetyl-4-methylbenzimidazole is isolated with a m.p. 170 ° C. Exit 57% of theory.
    Example 3.0.1 mol 5-carbomethoxy-2-mercaptobenzimidazole is dissolved in a mixture of 20 ml of water, 200 ml of iso-propanol and 0.2 mol of sodium hydroxide. Then 0.1 mol of hydrochloride. {Rmethyl-5-methylpyridine) is added and the mixture is heated under reflux at 82-85 ° C for 2 hours. The resulting sodium chloride is filtered and evaporated in vacuo. The residue is dissolved in acetone and treated with activated charcoal. Then the solution is evaporated and 2- 2- (5-methyl-pyridylmethylthio} -5 -carbomethoxybenzimidazole is isolated with mp 1401 {base). Exit 71% of theory.
    Example 4. OD mole of 5-propionyl-2-mercaptobenzimidazole is dissolved in a mixture of 20 ml of water, 200 ml of dimethylformamide and 0.2 mol of sodium hydroxide. Then 0.1 mol of 2-chloromethylpyridine hydrochloride is added and the mixture is heated under reflux at 153-155 ° C for 2 hours. The resulting sodium chloride is filtered and the solution is evaporated in vacuo. The residue is dissolved in acetone and treated with activated charcoal. The solution is evaporated and set aside.
    2- 2-pyridylmethylthioZ-5-propionyl, | benzimidazole with m.p. 130 ° C (base). Yield 62% of theory. Example 5. 0.1 mol of 5-propionyl-2-mercaptobenzimidazole is dissolved in a mixture of 20 ml of water, 200 ml of methanol and 0.2 mol of sodium hydroxide. Then 2-chloromethyl-5-methylpyridine hydrochloride is added and the mixture is heated under reflux
    at a temperature of 2 hours. The resulting sodium chloride is filtered and the solution is evaporated in vacuo. The residue is dissolved in acetone and treated with activated charcoal. The solution is evaporated and the (5-methyl) -pyridylmethylthio-5-propionylbenzimidazole is isolated with m.p. 126 ° C (base). Exit 68% of theory.
    Example 6. Example 5 is repeated with the difference that the reaction is carried out at a temperature. 40 C and a pressure of 200 mm Hg. Within 2.5 hours
    2-2- (5-methyl) -pyridylmethylthio-5-pro-espionylbenzimidazole is obtained with m.p. 12bs (base). Yield 62%
    theories.
    Example 7. 0.1 mol of 5-methyl-6-acetyl-2-mercaptobenzimidazole is dissolved in a mixture of 20 ml of water, 200 ml
    dimethyl sulfoxide and 0.2 mol of sodium hydroxide. Then 0.1 mol of 2-chloromethyl-5-methylpyridine hydrochloride is added and the mixture is heated under reflux at 190 ° C in
    for 2 hours. The sodium chloride formed is filtered and the solution is evaporated in vacuo. The residue is dissolved in acetone and treated with activated charcoal. An equivalent amount of concentrated hydrochloric acid is then added and (5-methyl) -pyridylmethylthio-5-methyl-6-acetyl-2-benzimidazole monohydrochloride with m.p. 145c (BUT), Yield 58% of theory.
    Similarly, for example, 1-7, compounds of the general formula are obtained.
    The results of examples 8-30 are shown below.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of producing benzimidazole derivatives of the general formula {I)
    and / or Het means 2-pyridyl substituted with methyl or chlorine and / or A means a group V or their salts, characterized in that the compound of formula (II)
    (I)
    net,
    (Yu where R and R are the same or different and mean hydrogen, halogen, alkyl with up to 4 carbon atoms, carboxyl, caralkoxy with up to 4 carbon atoms in the alkoxy group / me7oxy, hydroxy group, oxyalkyl with up to 4 carbon atoms in alkyl parts and alkanoyl with the number of carbon atoms up to 4, in any position; 2. hydrogen, alkanoyl with the number of carbon atoms up to 4, carbalkoxyl with the number of carbon atoms up to 4; A - the -SCHj and -5CH (CH3) / groups than the sulfur atom is bound to the benzimidazole group. Het. - 2-pyridyl, unsubstituted or substituted by methyl and chlorine, with If R and R are hydrogen, methyl, and halogen, then R 2. means alkanoyl with carbon number up to 4 or carb alkoxy with number of carbon atoms to where R, R, Rg have the above values; Z is SH or reactive esterified hydroxyl the group is reacted with a compound of the formula (III) z-CH-Het where R 3 is hydrogen or methyl; Het and Z are as defined above, in an aqueous organic medium at a temperature of 40-190 ° C in the presence of a base, followed by isolation of the desired product, in free form or in the form of salt. Sources of information taken into account in the examination 1. The patent of Hungary No. 156129, cl. 12p 6-10, published. 01.10.70.
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    同族专利:
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    法律状态:
    优先权:
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