• 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 concerns alpha -aminoacyl derivatives of phenyl-, phenoxy-, thiophenoxy- and phenylsulphinylalkanoic acids together with their amides, esters and pharmaceutically acceptable salts; processes for their preparation; and pharmaceutical compositions for therapeutic use in inhibiting the formation of thrombi and also in reducing the persistence of thrombi formed in the blood of warm blooded animals. Representative compounds of the invention are methyl 4-(aminoacetyl)phenoxyacetate, 4-(aminoacetyl)phenoxyacetic acid and methyl 4-(aminoacetyl)-thiophenoxyacetate, preferably as their hydrochlorides.
    公开号:SU722481A3
    申请号:SU782579897
    申请日:1978-02-13
    公开日:1980-03-15
    发明作者:Рональд Хьюджес Клиффорд；Джон Джексон Стефен；Престон Джон；Лесли Уолтон Питер
    申请人:Империал Кемикал Индастриз Лимитед (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing new derivatives of aminoketone or their salts, which have biological activity and can find application in medicine.
    The literature describes various derivatives of aminoketone, for example, the formula
    (О where R | is hydrogen, lower alkyl,
    R 2 is lower alkyl * consisting in the interaction of a compound of the formula
    with amine in an organic solvent [1].
    The aim of the invention is to develop; a method for producing new derivatives of aminoketones or their salts, which would have high biological activity.
    - / VoCHjCOR, ^ | ή
    - / H-OSNGSOYA / Y}
    The goal is achieved by the described method, which is based on the known reaction of the exchange decomposition of halogen derivatives ’with amines.
    According to the invention describes a method for producing new derivatives of aminoketone General formula 1
    H 2 NCHiC0 wherein R - IDN hydroxy- methoxy, consists in the fact that the compound of formula g with SPC where Q - halogen,
    R has the abovementioned meaning, are reacted with geksametichentetraminom in an inert solvent at 20-60 ° C followed by acidic hydrolysis of the resulting salt minutes at 40-100 C. and isolating the desired product in the free form or in salt form. Hydrolysis is usually carried out in the presence of alcohol and hydrochloric acid.
    The reaction with hexamine is usually carried out using equimolecular amounts of reagents, and tetrahydrofuran or chloroform can be used as a solvent.
    The most suitable salts are hydrochloride or hydrobromide, as well as citrate, lactate or acetate.
    Example!. A solution of 26 g of 4- (- (bromoacetyl) phenoxyacetic acid in 150 ml of chloroform was stirred as 14 g of hexamine was added.The mixture was stirred at room temperature for 3 days and then filtered. The solid was suspended in 250 ml of ethanol, 50 was added ml of hydrochloric acid and the mixture was stirred at room temperature for 18 hours, the mixture was then filtered and the filtrate was diluted with 1500 ml of diethyl ether, the solid thus obtained was filtered, washed with a mixture of ethanol and diethyl ether to obtain 4- (aminoacetyl) -phenoxyacetic hydrochloride ^ yield 40%, mp> 250 ° C, NMR (d e '-flMS Ό 100 MHZ using tet-25 ramethylsilane as the internal' standard) 8 7.0- 7.14, 7.92-8.06 each 2H (aromatic protons), 4.5 (2H, NHjCH ^ CO) and 4.81 (2H, -OCH g , COOH) ·, ·. 30
    Example 2. A solution of 6.7 g of methyl ~ 4- (chloroacetyl) phenoxyacetate in 100 ml of methylene chloride was stirred while 4.5 g of hexamine (hexamethylenetetramine) was added.
    The mixture was stirred at room temperature for 3 days.
    The resulting solid (9.0 g) was separated by filtration and mixed with 60 ml of methanol and 30 ml of concentrated hydrochloric acid at room temperature for 60 hours, and then the resulting solid (5.1 g) was separated by filtration. this solid is dissolved in 100 ml of cold methanol, the solution is filtered off and the filtrate is evaporated to 30 ml.
    Methyl 4- (aminoacetyl) phenoxyacetβτθ hydrochloride (2.0 g, mp 202204 ° C) is separated off upon cooling.
    Example 3. Using the procedure described in example 2, but replacing concentrated hydrochloric acid with a 50% solution of sulfuric acid, methyl 4- (aminoacetyl) phenoxyacetate sulfate is obtained as a solid residue, yield 30-40%, mp. 125-128 ° C.
    权利要求:
    Claims (3)
    [1]
    Culinary amounts of reagents, tetrahydrofuran or chloroform can be used in KaiiecTBe solvent. The most suitable salts are hydrochloride or hydrobromide, as well as citrate, lactate or acetate. Example. A solution of 26 g of 4- (- (bromoacetyl) phenoxyacetic acid in .150 ml of chloroform is stirred as 14 g of hexamine is added. The mixture is stirred at room temperature for 3 days and then filtered. The solid is suspended in 250 ml of ethanol the mixture is then filtered and the filtrate is diluted with 1500 ml of diethyl ether. The solid thus obtained is filtered, washed with a mixture of ethanol and diethyl ether to obtain 4 - (aminoacetyl) -phenoxyacetic acid hydrate, 40% yield, mp 250 C, NMR (dg-flMS 0.100 MHZ, using thermal silane as an internal standard) 8 7.0-7.14, 7.92-8.06 each 2H (aromatic protons}, 4,5 (2H, NHjCH CO) AND 4.81 (2H, -OCH COOH) “Example
    [2]
    2. A solution of 6.7 g of meth-4- (chloroacetyl) phenoxyacetate in 100 ml of methylene chloride is stirred during the addition of 4.5 g of hexamine (hexametoethylenetetramine). The mixture is stirred at room temperature for 3 days. The resulting solid (9,, O g) is separated by filtration and mixed with 60 ml of methanol and 30 ml of concentrated hydrochloric acid at room temperature for 60 hours, and then the resulting solid (5.1 g) is separated by filtration. The solid is dissolved in 100 ml of cold methanol, the solution is filtered off and the filtrate is evaporated to 30 ml. Methyl 4- (aminoacetyl) phenoxyacetate hydrochloride (2.0 g, mp. 202204 ° C) is separated by cooling. Example
    [3]
    3. Using the procedure described in Example 2, but replacing concentrated hydrochloric acid with a 50% solution of sulfuric acid, methyl 4- (aminoacetyl) phenoxyacetate sulfate is obtained in the form of a solid residue, yield 30-40%, mp. 125-128 ° C. The invention method for producing amino ketone derivatives of the general formula HnCNHCO - / y OCH2SoB .VJ where R is hydroxy or methoxy radical, or their salts, characterized in that the compound of the formula oCHNCov qCHzCo where Q is halogen in an inert solvent at 20-60 s, followed by acidic hydrolysis of the obtained salt at 40100 ° C and the separation of the target product in free form or as a salt. Sources of information taken into account in the examination 1. USSR Patent No. 385435, cl. From 07 to 97/10, 1973, issued by the foreign company Dr. Karl Tome GMbH (Germany).
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    同族专利:
    公开号 | 公开日
    LU76251A1|1977-12-13|
    SE7613079L|1977-05-26|
    ATA870976A|1978-08-15|
    IL50904A|1980-02-29|
    PL105491B1|1979-10-31|
    NZ182581A|1978-09-20|
    DD127474A5|1977-09-28|
    JPS6360004B2|1988-11-22|
    JPS5265240A|1977-05-30|
    DE2653635A1|1977-06-02|
    ES465152A1|1978-10-01|
    DK531276A|1977-05-26|
    GB1559977A|1980-01-30|
    PT65892B|1978-05-18|
    NO764012L|1977-05-26|
    PL105799B1|1979-10-31|
    AU1962576A|1978-05-25|
    PT65892A|1976-12-01|
    AT348993B|1979-03-12|
    CS196333B2|1980-03-31|
    JPS61158922A|1986-07-18|
    IE44030B1|1981-07-29|
    US4105790A|1978-08-08|
    IE44030L|1977-05-25|
    FR2332747A1|1977-06-24|
    CA1068695A|1979-12-25|
    DE2653635C2|1986-10-02|
    FR2332747B1|1980-03-14|
    AU503657B2|1979-09-13|
    NL7613081A|1977-05-27|
    FI763399A|1977-05-26|
    BE848707A|1977-05-24|
    ES453632A1|1978-03-16|
    IN145003B|1978-08-12|
    ZA766696B|1977-10-26|
    AR215871A1|1979-11-15|
    PL193861A1|1978-03-28|
    CH624383A5|1981-07-31|
    JPS6120538B2|1986-05-22|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US7994315B2|2005-07-22|2011-08-09|Mitsubishi Tanabe Pharma Corporation|Intermediate compound for synthesizing pharmaceutical agent and production method thereof|CH543472A|1969-01-31|1973-10-31|Orchimed Sa|Process for the preparation of phenoxyalkylcarboxylic acids|JPH028457U|1988-07-01|1990-01-19|
    JPH02130656U|1989-03-31|1990-10-29|
    US5348969A|1992-04-03|1994-09-20|Bristol-Myers Squibb Company|Diphenyloxazolyl-oxazoles as platelet aggregation inhibitors|
    US6147216A|1993-06-25|2000-11-14|Merrell Pharmaceuticals Inc.|Intermediates useful for the preparation of antihistaminic piperidine derivatives|
    CN1275916C|1993-06-25|2006-09-20|阿温蒂斯公司|Novel intermediates useful for the preparation of antihistaminic piperidine derivatives|
    US6683094B2|1998-07-02|2004-01-27|Aventis Pharmaceuticals Inc.|Antihistaminic piperidine derivatives and intermediates for the preparation thereof|
    US6673933B2|1998-07-02|2004-01-06|Aventis Pharmaceutical Inc.|Antihistaminic piperidine derivatives and intermediates for the preparation thereof|
    FR2880887B1|2005-01-14|2009-01-30|Merck Sante Soc Par Actions Si|HYDROXYPHENOL DERIVATIVES, PROCESSES FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND THERAPEUTIC APPLICATIONS|
    WO2016009871A1|2014-07-16|2016-01-21|株式会社Adeka|Photosensitive composition|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB48402/75A|GB1559977A|1975-11-25|1975-11-25|Amines|
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