• 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 method of obtaining H-
    公开号:SU1195909A3
    申请号:SU833593066
    申请日:1983-05-23
    公开日:1985-11-30
    发明作者:Мерц Герберт；Лангбейн Адольф；Штокхаус Клаус
    申请人:Берингер Ингельгейм Кг.(Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of a new mink derivative of symforhon M- (2-methoxyeth-1) -noroxy morphone of the formula -N-CH-i-CH-O-CH but; or its acid addition salts having analgesic properties. The aim of the invention is to obtain a novel noroxymorphone derivative, which does not cause addiction and has a higher analgesic activity as compared with the known morphine-like compounds. Example 1. N- (2-Methoxyethyl) noroxymorphone. 1. Preparation of the starting compound. A. Ethylene ketal N-methoxy-acetylnormoxymorphane. To an intensively mixed suspension of a suspension of 66.2 g (0.2 mol) ethylene ketal of noroxymorphone in a mixture of 662 MP of absolute methyl chloride and 80 ml of triethylamine, cooled with ice, a solution of 47.8 g is added dropwise over 2 hours (0.44 mol) of methoxyacetyl chloride in 331 ml of absolute methylene chloride. A clear solution is formed which is boiled under reflux for 1 hour. After cooling, the methylene chloride solution is rinsed 3 times with water, dried with sulphate and evaporated in a rotary evaporator, completing the process in a vacuum. The residue was dissolved in 100 mp of toluene and the solution was re-evaporated. The ethylene ketal of N-labels of siacetyl-noroxymorphone obtained as a crystalline residue (91.2 g) without intermediate purification is used in the next stage. B. Ethylene ketal H- (2-methoxyethyl1 noroxymorphone. The residue obtained in the previous step, heated, is dissolved in 1400 ml of absolute tetrahydrofuran. The solution, after cooling to 25-30 ° C, is added dropwise over 4 hours to the vigorously stirred suspension g (0 , 63 mol) lithium aluminum hydride in 600 ml of absolute tetrahydrofuran is cooled to ensure that the reaction temperature does not exceed 3035 s. The reaction mixture is subsequently boiled under reflux for 2 hours. Then cooled with vigorous stirring is added dropwise 300 MP water. Pos add 2,6 l of the whole; a solution of tartrate diammonin is stirred for 2 h. Then the lighter solution of tetrahydrofuran is separated and evaporated in vacuo.The resulting aqueous solution is extracted twice with methylene chloride (400 ml). The residue of the tetrahydrofuran fraction is solution in methylene chloride extracts, the resulting solution is twice washed with water (400 l each), dried with sodium sulfate and evaporated in a vacuum.The ethylene ketal of M- (2-methoxyethyl) -noroxymorphone obtained as a residue (69 g) is subjected after further purification uyuschemu cleavage. 2. Preparation of the target product, N- (2-methoxyethyl) -noroxymorphone hydrochloride. For the cleavage of the ketal, the residue obtained in the preceding stage is refluxed in a mixture of 70 ml of water with 40 ml of concentrated hydrochloric acid for 1 hour. The light brown solution is cooled and 800 ml of acetone is added. In this case, N- (2-methoxy-ethyl) -oproxymphophan hydrochloride is precipitated as crystals. After storage overnight in the refrigerator, it is sucked off, rinsed with acetone, and dried at -60 ° C. 74.0 g are obtained (70.7%) %) hydrochloride of N- (2-methoxyethyl) -noroxymorphone with so pl. . After recrystallization from a mixture of 167 ml of water (dissolving is carried out at boiling point) and 1.4 l of acetone (which is added after cooling the aqueous solution, 62.0 g of pure substance is obtained with a mp of 265-267 s. Obtained after repeated recrystallization from methanol, the product melts at 269-270 ° C. EXAMPLE 2 K- (2-methoxyethyl) noroxymorphone 1.4 g (3.67 mmol) of H- (2-methoxyethyl) noroxymorphone hydrochloride are dissolved in 20 ml of a mixture of methanol and water (1: 1). While stirring, 3.0 ml of 2 nam are added dropwise to the solution.
    权利要求:
    Claims (1)
    [1]
    The method of obtaining the I- (2-me — toxethyl - noroxymorphon formula, or its acid addition salt, characterized in that the compound of the formula rN ~ CH 2 —CHj — O — CHj is subjected to water and concentrated hydrochloric acid in a ratio of 7: 4 by volume followed by isolation of the target product in the form of a base or an acid addition salt.
    interaction with the mixture
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    同族专利:
    公开号 | 公开日
    ES522897A0|1984-03-16|
    KR840005146A|1984-11-03|
    DE3220831A1|1983-12-08|
    JPS591487A|1984-01-06|
    NO158579B|1988-06-27|
    FI831941L|1983-12-04|
    EP0096279B1|1985-11-06|
    NO158579C|1988-10-05|
    GR78273B|1984-09-26|
    KR900006754B1|1990-09-20|
    FI78101B|1989-02-28|
    JPH0373552B2|1991-11-22|
    ES8403487A1|1984-03-16|
    PH19518A|1986-05-14|
    AU1531483A|1983-12-08|
    PL242312A1|1985-04-09|
    DK156068C|1989-11-06|
    NO831995L|1983-12-05|
    US4473573A|1984-09-25|
    NZ204451A|1986-07-11|
    IE831299L|1983-12-03|
    PT76805A|1983-07-01|
    IL68872D0|1983-10-31|
    CA1196633A|1985-11-12|
    AU558319B2|1987-01-29|
    DD209834A5|1984-05-23|
    SG58788G|1989-03-10|
    DK250783A|1983-12-04|
    PL139569B1|1987-02-28|
    EP0096279A1|1983-12-21|
    IE55232B1|1990-07-04|
    GB2121041B|1985-09-11|
    HK1389A|1989-01-13|
    FI78101C|1989-06-12|
    ZA833981B|1985-01-30|
    DK250783D0|1983-06-02|
    HU185832B|1985-04-28|
    GB8315292D0|1983-07-06|
    PT76805B|1986-04-09|
    FI831941A0|1983-05-31|
    DE3361165D1|1985-12-12|
    CZ410691A3|1993-02-17|
    GB2121041A|1983-12-14|
    CS236882B2|1985-05-15|
    DK156068B|1989-06-19|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3332950A|1963-03-23|1967-07-25|Endo Lab|14-hydroxydihydronormorphinone derivatives|
    DE2538075A1|1975-08-27|1977-03-17|Boehringer Sohn Ingelheim|N-TETRAHYDROFURFURYL NOROXYMORPHONES, THEIR ACID ADDITIONAL SALTS, THE MEDICINAL PRODUCTS AND THE METHOD FOR THEIR MANUFACTURING|DE4132159A1|1991-09-27|1993-04-01|Boehringer Ingelheim Kg|14-HYDROXY-N--7,8-DIHYDROMORPHINE AND -NORISOMORPHINE, PROCESS FOR THEIR PREPARATION AND THEIR USE AS DRUG|
    HUE043963T2|2009-12-04|2019-09-30|Alkermes Pharma Ireland Ltd|Morphinan derivatives for the treatment of drug overdose|
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    US9211293B2|2011-12-15|2015-12-15|Alkermes Pharma Ireland Limited|Opioid agonist antagonist combinations|
    WO2014190271A2|2013-05-24|2014-11-27|Alkermes Pharma Ireland Limted|Methods for treating depressive symptoms|
    AU2014268361B2|2013-05-24|2018-09-06|Alkermes Pharma Ireland Limited|Morphan and morphinan analogues, and methods of use|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19823220831|DE3220831A1|1982-06-03|1982-06-03|N--NOROXYMORPHONE, ITS ACID ADDITION SALTS, MEDICINAL PRODUCTS CONTAINING THEM AND METHOD FOR THE PRODUCTION THEREOF|
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