• 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:
    The invention relates to heterocyclic compounds, in particular to the preparation of 4,5-dihydroimidazo-4,5, lj-kjri 1 -benzazepin-2, B, 6H -dione (1), which has a high antihypertensive, hypotensive and vasodilator activity. The goal is to develop a method for producing new intermediates for the synthesis of compounds with pharmacological properties. Compound preparation
    公开号:SU1384201A3
    申请号:SU864015498
    申请日:1986-01-30
    公开日:1988-03-23
    发明作者:Фреше Даниель；Неделек Люсьен；Плассар Ги；Лесли Браун Неил
    申请人:Руссель-Юклаф (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to the field of 1 h, to obtain a new 4,5-dihydroimidazoyl residue C4,5,1-jk 1 P-benzazepine-2,. 6H acid to the dione, which is the starting material in the synthesis of 6-amino -7-hydroxy-4,5,6,7-tetrahydro-imidazo 4,5,1-jk benzazepin-2 1H-it has a high antihypertensive and hypotensive as well as vasodilator. Yu activity.
    The aim of the invention is to develop, on the basis of a known method, a method of producing new intermediates for the synthesis of compounds that have a pharmacological properties. .
    Example 1,4,5-Dihydroimide-, 5,1-j-k P1-benzazepin-2 ,, 6H-dion.20
    A. 2,3-Dihydro-3- (1-meiylethenyl) -2-oxo-1H-benzimidazole-1-butyric acid ethyl ester.
    one .
    5.75 g of 50% is stirred, methanol is distilled off and the pH 1 is concentrated with concentrated hydrochloric acid at 1.5 hours of ice water, the precipitate is filtered off with suction, washed with water and 18.1 g of product are collected with a melting point of 180 ° C .
    Recrystallized in iso nol and obtain 15.2 g of a target product with a melting point
    G, 4,5-Dihydroimidazo 4,5,1 tl-benzazepin-2 ,,
    For 1 h and 30 min, heat with reflux 300 with chloroform, 15.2 cm of chloride and 15.2 g of the acid obtained in 100%. 18.4 g of chlorine aluminum are cooled to 15 seconds and drilled at one time. Stir in water at room temperature and mix the mixture with 600 cm of ice water, which burns 15 cm of concentrated acid, and mix with 5 min.
    of sodium chloride in oil in 10 cm of dimethyl- 25, the resulting precipitate of formamide is sucked in, added over 45
    9.9 g of crude target product are obtained. Collect 2.5 g of uterine tubes. The total amount of the products obtained is recrystallized in propanol. Obtain 8.5 g of target product with a melting point of 238 C.
    min, above temperature at 20 C + 2.19 g of 1,3-dihydro-1- (1-methyl-ethylene) -2H-benzimidazol-2-ona in 150 cm of dimethylformamide and maintain stirring for another 0.5 h. 23.4 g of 4-bromo-butyric acid ethyl ester is added over 15 minutes and stirred for an additional 4 hours at room temperature. Pour the reaction mixture into 800 cm of ice-water, extract with ether, wash with water, resist and concentrate to dryness. Obtain 33 g of the desired product.
    B. Ethyl ester of 2, 3-dihydro-2-oxo-1H-benzimidazole-1-butyric acid.
    Mix 15.5 cm of sulfuric acid to °
    155 cm of ethanol, cooled to 0 ° C and 5 ° C, 31.4 g of the obtained product are added and stirred for 5 hours at 0 ° C and 5 ° C. Neutralized with sodium hydroxide solution, the reaction mixture is poured onto 1.5 liters of ice water and stirred for 5 minutes . The mixture is filtered off with suction, washed with water and 22 g of the expected product are obtained with a melting point of 88 ° C.
    B, 2, 3-Dihydro-2-oxo-1P-benzimidazole-1-butanoic acid.
    22 g of the product obtained in step B are dissolved in 22 cm of sodium hydroxide solution and 200 cm of methanol. The mixture is heated under reflux for 1 hour, the residue is acidified to
    methanol was distilled off and 1.5 hour ice water was collected. Sub pH 1 with concentrated hydrochloric acid, the precipitate formed is filtered off with suction, washed with water and 18.1 g of product are collected with a melting point of 180 ° C.
    It is recrystallized in isopropanol to obtain 15.2 g of the expected product with a melting point.
    G, 4,5-Dihydroimidazo 4,5,1-j-k tl-benzazepin-2, 6H -dione.
    For 1 hour and 30 minutes, 300 cm of chloroform, 15.2 cm of thionyl chloride and 15.2 g of the acid obtained in stage P are heated under reflux. The mixture is cooled to 15 seconds and 18.4 g of aluminum chloride are added at a time. The mixture is stirred for 4 hours at room temperature and the mixture is poured onto 600 cm of ice-cold water containing 15 cm of concentrated hydrochloric acid, stirred for 5 minutes, the precipitate formed is sucked off
     and
    suck the precipitate
    9.9 g of crude desired product are obtained. Collect 2.5 g of stock solutions. The total amount of the products obtained is recrystallized in isopropanol. 8.5 g of the expected product are obtained with a melting point of 238 C.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining 4,5-digschrohimidazo-4,5,1-jk l -benzazepin-2,7-1H, 6H -dione, characterized in that 1,3-dihydro-1- (1-methyl- ethynyl) -2H-benzimidazol-2-one of formula
    H C C CH3
    subjected to interaction with ethyl ester of 4-bsmcelic acid of formula
    Vg-Ssp,), -
    in the presence of an alkali metal hydride as a base, the resulting 2,3-dihydro-3- (1-methylethenyl) -2-oxo-1H-benzimidazole-1-butyric acid ethyl ester of the formula
    1384201 .4
    C Op-HjC-CHi is removed with caustic soda in an alcohol medium to the acid of formula
    5НООС-СН2-СН2
    SNS
    subjected to acid hydrolysis in alcohol, the resulting 2,3-dihydro-2-oxo-1H-benz-.-imidazole-1-butyric acid ethyl ester of the formula CjHs-OjO-H C-tJHi
    i which is then converted into halogen f-ariD and treated with chloride
    aluminum to cyclize the side chain.
    类似技术:
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    同族专利:
    公开号 | 公开日
    IL69993D0|1984-01-31|
    DK163734C|1992-08-31|
    AU559422B2|1987-03-12|
    FI833697A|1984-04-13|
    AU2005383A|1984-04-19|
    EP0107569A1|1984-05-02|
    DD215784A5|1984-11-21|
    PT77469A|1983-11-01|
    FR2534257B1|1984-12-28|
    IE832387L|1984-04-12|
    US4585770A|1986-04-29|
    DE3370332D1|1987-04-23|
    HU188499B|1986-04-28|
    ES8405802A1|1984-06-16|
    IE59441B1|1994-02-23|
    ES526390A0|1984-06-16|
    KR900006753B1|1990-09-20|
    FI76340B|1988-06-30|
    IL69993A|1987-10-30|
    GR78731B|1984-10-02|
    FI833697A0|1983-10-11|
    PT77469B|1986-05-07|
    CA1222246A|1987-05-26|
    ZA837480B|1984-11-28|
    MX8495A|1993-09-01|
    DK466483D0|1983-10-11|
    DK163734B|1992-03-30|
    SU1287753A3|1987-01-30|
    CA1216847A|1987-01-20|
    NZ205918A|1985-12-13|
    JPH0454671B2|1992-08-31|
    FR2534257A1|1984-04-13|
    FI76340C|1988-10-10|
    AT25981T|1987-04-15|
    DK466483A|1984-04-13|
    KR840006484A|1984-11-30|
    EP0107569B1|1987-03-18|
    PH20031A|1986-09-04|
    JPS59130289A|1984-07-26|
    引用文献:
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    EP0034989B1|1980-02-26|1983-10-05|Roussel-Uclaf|Cycloheptindolol derivatives and their acid-addition salts, their preparation, their use as medicines and composition containing them|AU616390B2|1986-12-11|1991-10-31|Hoechst Roussel Vet S.A.|Zootechnical compositions containing a beta-adrenergic|
    FR2608046B1|1986-12-11|1989-03-31|Roussel Uclaf|ZOOTECHNIC COMPOSITIONS CONTAINING A DERIVATIVE OF 6-AMINO 7-HYDROXY 4,5,6,7-TETRAHYDROIMIDAZO / 4,5, 1-J-K / / 1 / BENZAZEPIN-2--ONE|
    FR2608047B1|1986-12-11|1990-08-31|Roussel Uclaf|ZOOTECHNIC COMPOSITIONS CONTAINING A DERIVATIVE OF 6-AMINO 7-HYDROXY 4,5,6,7-TETRAHYDROIMIDAZO / 4,5,1-J-K / / 1 / BENZAZEPIN-2--ONE|
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    GB8806449D0|1988-03-18|1988-04-20|Janssen Pharmaceutica Nv|Antiviral hexahydroimiazobenzodiazepin-2-ones|
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    FR2735474B1|1995-06-13|1997-08-08|Roussel Uclaf|ZILPATEROL HYDROCHLORIDE IN A PARTICULAR CRYSTALLIZED FORM, ITS PREPARATION PROCESS AND THE INTERMEDIATE PRODUCTS USED|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8217054A|FR2534257B1|1982-10-12|1982-10-12|
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