• 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:
    4-(Polyalkoxyphenyl)-2-pyrrolidones of the formula <IMAGE> wherein R1 and R2 are hydrocarbon; R3 is hydrogen or methoxy; R is O-alkyl, O-aryl, O-aralkyl, NH2, NH-alkyl, NH-aryl, NH-aralkyl, N(alkyl)2, N(aryl)2 or <IMAGE> AND X is O or S, are neuropsychotropic agents.
    公开号:SU795465A3
    申请号:SU762385904
    申请日:1976-07-28
    公开日:1981-01-07
    发明作者:Хут Андреас；Шмихен Ральф；Кер Вольфганг；Паленшат Дитер；Пашельке Герт；Вахтель Хельмут
    申请人:Шеринг Аг (Фирма)；
    IPC主号:
    专利说明:

    (54) METHODS OF 4- (POLYALCOXYPHENYL) 2-PYRROLIDONES
    one
    A method for preparing novel pyrrolidine derivatives, which may be used in the pharmaceutical industry, is proposed.
    The reaction of the acylation of amines 1 is widely described in the literature.
    The aim of the invention is to develop a method based on the known reaction for the preparation of new compounds with high pharmacological activity.
    The proposed method for the preparation of 4- (polyalkoxyphenyl) -2-pyrrolidones of the general formula
    oni "go
    at
    0
    "3
    where R and R are the same or different and mean alkyl C.-C or cycloalkide
    R3 is 0-alkyl, o-aryl-o-ar. Alkyl Cg, NH2-, NH-alkyl, CN-aryl, MH-aralkyl, C - (alkyl), M - aryl, and
    alkyl
    N
    an alkyl group
    aryl
    has up to five carbon atoms, and the aryl and aralkyl groups have up to eight carbon atoms, is that 4- (polyalkoxyphenyl) -2-pyrrolidones of the general formula
    where K and R2 are either R and R. or hydrogen, are acylated with a reactive acid derivative at a temperature from room temperature to the boiling point of the reaction mixture.
    The desired product is either isolated, or in the case when R is free NH-rpynna, treated with alkyl, aralkyl or aryl halide in the process of sodium hydride at a temperature from to room temperature.
    Benzyl ester of chlorogolic acid, chlorosulfonyl isocyanate, alkyl, aryl or aralkyl isocyanate is used as a reactive acid.
    The compounds thus obtained possess high biological activity and can be used for the synthesis of pharmaceutical preparations.
    Example 1. 2.21 g (10 mmol of 4- (g, 4-dimethoxyphenyl) pyrrolidone are stirred with 1 g of anhydrous sodium carbonate and 30 ml of ethyl chlorogolic acid ester for 16 hours at 100 ° C. Obtain 1.09 g of ethyl ether 4- (3, 4-dimethoxyphenyl -2-pyrrolidone-1-carboxylic acid with mp 88-90 ° C (acetic eff / petroleum ether).
    Example 2. 2.21 g of 4- (3,4-dimethoxyphenyl) -2-pyrrolidone are reacted in analogy to example 1 with chlorosol acid benzyl ether and purified by methods of chromatography ha silica gel with benzene / ethyl acetate (1: 1). Obtain 1.24 g of benzyl ester of 4- (3,4-dimethoxyphenyl) -2-pyrrolidone-1-carboxylic acid with so pl. 8b-87s (ethyl acetate / petroleum ether.
    In a similar manner, 4- (3-cyclopentyloxy-4-methoxyphenyl) -2-pyrrolidone-1-carboxylic acid benzyl ester is synthesized from 4- (3-cyclopentyloxy-4-methoxyphenyl) -2-pyrrolidone as an oil and benzyl ether
    4- (3-isobutyloxy-4-methoxyphenyl -2-pyrrolidone-1-carboxylic acid from 4- (3-isobutyloxy-4-methoxyphenyl) -2-pyrrolidone (mp. 76-78 ° С, ethyl acetate / petroleum ester). 4- (3, 4-Dimethoxyphenyl) -2-pyrrolidone-1-carboxylic acid 2-methoxycarbonylphenyl ester from 4-3- (3,4-dimethoxyphenyl) -2-pyrrolidone and 2-methoxycarbonylphenyl chloroethyl ester is also prepared in a similar way. acid in the form of oil.
    Example 3. 0.22 g of 4- (3,4-dimethoxyphenyl) -2-pyrrolidone is mixed in 10 methyl chloride with 3 ml of chlorosulfonyl isocyanate and stirred 5 for 1.5 hours at room temperature. The mixture is treated as usual with methylene chloride and purified by chromatography on silica gel with chloroform / acetone (1: 1). This gives 0.026 g of 4- (3,4-dimethoxyphenyl) -2-pyrrolidone-1-carboxylic acid amide with mp. 125-127 0 (methanol).
    Example 4. Amides of 4- (3,4-dimethoxyphenyl) -2-pyrrolidone-1-carboxylic acid.
    2.21 g of 4-13,4-dimethoxyphenyl -2-pyrrolidone are heated with an isocyanate of the general formula R-NCO (an excess of about 10-fold) for 2.5 hours to boil and then evaporated in vacuo.
    Depending on the isocyanate used, 1-carboxylic acid amides are obtained, which are listed in the table.
    1.47 95-98 acetic ether / diiso 1.53 105-107 propyl ether acetic ether / petroleum ether
    权利要求:
    Claims (2)
    [1]
    2.62 110-112 acetic ether / petro2, 8Lay oil ester The claims 1. Method for preparing 4- (polyalkoxy-55 phenyl) -2-pyrrolidrene of the general formula ORi, about 65 where R and R2 are the same sludge and are different and R alkyl or cycloalkyl Rg o-alkyl, o-aryl, o-aralkyl. Cg, NHg-, NH-alkyl, NH-aryl, HH-aralk11p, M- (alkyl) l, M- (aryl) 2I. Alkyl N. : wherein the alkyl group has up to five atoms of the carbon, and the aryl and aralkyl groups have up to eight carbon atoms, which is distinguished by the fact that 4-polyalkoxyphenyl) -2-pyrrolidones of the formula -On. where ", and R ;, denote either R. and R or hydrogen, acylated with reactive acid and water at temperatures from room temperature to the boiling point of the reaction mixture and is targeted. the product is added or, in the case when the RJ-free HH-group is treated with alkyl, aralkyl or aryl halide in the presence of sodium hydride at a temperature from to room temperature.
    [2]
    2. A method according to claim 1, characterized in that chlorous acid benzyl ester, chlorosulfonyl isocyanate, alkyl, aryl or aralkyl isocyanate is used as a reactive acid derivative. Sources of information taken into account during the examination Methoden des Organischen Chemic, t. 11/1, 1957, p. 928-935.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU795465A3|1981-01-07|Method of preparing 4-|-2-pyrrolidones
    Diago-Meseguer et al.1980|A new reagent for activating carboxyl groups; preparation and reactions of N, N-bis [2-oxo-3-ox-azolidinyl] phosphorodiamidic chloride
    SU1333234A3|1987-08-23|Method of producing the derivatives of n-phenylbenzamide or salts thereof
    GB1575709A|1980-09-24|1,1-cycloalkyldiacetic acid imide derivatives and their use for preparing 1-aminomethyl-1-cycloalkylacetic acids
    JP2018058895A|2018-04-12|-7-oxo-6-sulfooxy-2-[|-pyrrolidine-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]octane
    RU1797607C|1993-02-23|Process for preparing [@]-@@@-ethyl-2-oxo-1-pyrrolidine acetamide
    US4032559A|1977-06-28|N,2-dicyanoacetimidates
    US4758575A|1988-07-19|Bi-2H-pyrroli|nediones
    US4239709A|1980-12-16|Process for preparing optically active oxazaphosphorins
    US4497952A|1985-02-05|Process for the production of |-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline derivatives
    Ye et al.2003|Reaction of nitrile oxides with vinylphosphonate: A facile, regioselective approach to 5‐phosphonyl‐4, 5‐dihydroisoxazoles
    Studer et al.1995|Preparation of either enantiomer of 1, 2-diaminoalkane-2-phosphonic acid derivatives
    CN108752243B|2020-03-20|1, 4-naphthoquinone derivative and preparation method and application thereof
    ES471952A1|1979-02-01|Process for the production of N-substituted alpha -ketocarboxylic acid amides
    SU845778A3|1981-07-07|Method of preparing 5-puenyl-1h-banzazepins or their salts
    SU1318156A3|1987-06-15|Method for producing 1-benzylazetidine-3-ol
    SU660587A3|1979-04-30|Method of obtaining alkanolamines or salts thereof
    US4908464A|1990-03-13|Process for the production of 1,3,2-oxazaphosphorinanes
    Liu et al.2005|Synthesis of 1-| alkylphosphonic monoesters
    SU558639A3|1977-05-15|Method for preparing aminooxyhydroxamic acid derivatives or their salts
    SU1042619A3|1983-09-15|Process for preparing enamines of the series 7-oxo-4-thia-2,6-diazabicyclo|hept-2-ene
    US4545935A|1985-10-08|Amidoalkylation reactions of anilines
    SU436818A1|1974-07-25|The method of obtaining 0, -substituted derivatives of aryl | carbamoyl | - - | -2-hydroxylamines
    IE65888B1|1995-11-29|3-|-2-Methoxymethyl-propanol derivatives
    US3923827A|1975-12-02|Preparation of 4-imidazolin-2-ones
    同族专利:
    公开号 | 公开日
    JPS612660B2|1986-01-27|
    SE407799B|1979-04-23|
    ES451518A2|1977-10-01|
    DD126894A6|1977-08-17|
    IE43723L|1977-03-18|
    FR2324299B2|1980-02-01|
    CH623571A5|1981-06-15|
    AT349459B|1979-04-10|
    US4153713A|1979-05-08|
    JPS5236659A|1977-03-22|
    HU173117B|1979-02-28|
    DK157919B|1990-03-05|
    ATA690776A|1978-09-15|
    DE2541855A1|1977-03-31|
    GB1563398A|1980-03-26|
    NL7610300A|1977-03-22|
    SE7610275L|1977-03-19|
    DK157919C|1990-08-06|
    FR2324299A2|1977-04-15|
    CS225802B2|1984-02-13|
    IE43723B1|1981-05-06|
    CA1077496A|1980-05-13|
    BE846335R|1977-03-17|
    DK408676A|1977-03-19|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    CA709405A|1965-05-11|Parke, Davis And Company|Methods for producing pyrrolidine compounds|
    US2975193A|1959-06-18|1961-03-14|Parke Davis & Co|Organic amine compounds and method of obtaining the same|
    FR1516776A|1966-07-21|1968-03-15|Rhone Poulenc Sa|New pyrrole derivatives and their preparation|
    US3635982A|1969-04-08|1972-01-18|American Home Prod|Amino-substituted-quinoxalinyloxazolidines and -oxazines|
    US3644398A|1969-04-11|1972-02-22|Robins Co Inc A H|1-carbamoyl-3-phenylpyrrolidines|
    GB1350582A|1970-07-24|1974-04-18|Ucb Sa|Cerivatives of 2-pyrrolidinone|
    US3956314A|1970-07-24|1976-05-11|U.C.B., Societe Anonyme|Derivatives of 2-pyrrolidinone|
    JPS5232064B2|1972-06-14|1977-08-19|
    DE2413935C2|1974-03-20|1988-05-26|Schering Ag, 1000 Berlin Und 4709 Bergkamen, De|
    JP4916870B2|2006-12-25|2012-04-18|公益財団法人鉄道総合技術研究所|Voltage drop type pantograph contact force evaluation device|CA1124247A|1979-08-09|1982-05-25|Hoffmann-La Roche Limited|Pyrrolidine derivatives|
    HU215433B|1986-04-29|2000-05-28|Pfizer Inc.|Process for producing new 2-oxo-5-phenyl-pyrimidin derivatives|
    US5459145A|1988-01-19|1995-10-17|Pfizer Inc.|Calcium independent camp phosphodiesterase inhibitor antidepressant|
    YU162789A|1988-09-01|1990-12-31|Lonza Ag|2-aza-4- spiro/4,5/decan-3-ones|
    US5395935A|1992-05-08|1995-03-07|Pfizer Inc.|Endo-bicyclo[2.2.1]heptan-2-ol and derived pharmaceutical agents|
    JP2578001B2|1989-12-11|1997-02-05|明治製菓株式会社|Anti-dementia drug|
    US5547979A|1992-03-30|1996-08-20|Smithkline Beecham|TNF inhibition|
    US5420154A|1990-08-03|1995-05-30|Smithkline Beecham Corp.|TNF inhibitors|
    DE4032055A1|1990-10-05|1992-04-09|Schering Ag|METHOD FOR PRODUCING OPTICALLY ACTIVE 4-ARYL-2-PYRROLIDINONES|
    DE69221794T2|1991-01-21|1998-03-19|Shionogi Seiyaku Kk|3-BENZYLIDEN-1-CARBAMOYL-2-PYRROLIDONE ANALOG|
    US5514678A|1992-03-26|1996-05-07|E. I. Du Pont De Nemours And Company|Arthropodicidal 1,2,4-triazinyl amides|
    GB9212673D0|1992-06-15|1992-07-29|Celltech Ltd|Chemical compounds|
    GB9222253D0|1992-10-23|1992-12-09|Celltech Ltd|Chemical compounds|
    US5622977A|1992-12-23|1997-04-22|Celltech Therapeutics Limited|Tri-substitutedderivatives and pharmaceutical compositions containing the same|
    GB9226830D0|1992-12-23|1993-02-17|Celltech Ltd|Chemical compounds|
    GB9304919D0|1993-03-10|1993-04-28|Celltech Ltd|Chemical compounds|
    GB9304920D0|1993-03-10|1993-04-28|Celltech Ltd|Chemical compounds|
    US5665754A|1993-09-20|1997-09-09|Glaxo Wellcome Inc.|Substituted pyrrolidines|
    GB9326173D0|1993-12-22|1994-02-23|Celltech Ltd|Chemical compounds and process|
    WO1995017399A1|1993-12-22|1995-06-29|Celltech Therapeutics Limited|Trisubstituted phenyl derivatives, processes for their preparation and their use as phosphodiesteraseinhibitors|
    US5672622A|1994-04-21|1997-09-30|Berlex Laboratories, Inc.|Treatment of multiple sclerosis|
    US6060501A|1994-06-02|2000-05-09|Schering Aktiengesellschaft|Combined treatment of multiple sclerosis|
    US6245774B1|1994-06-21|2001-06-12|Celltech Therapeutics Limited|Tri-substituted phenyl or pyridine derivatives|
    US5786354A|1994-06-21|1998-07-28|Celltech Therapeutics, Limited|Tri-substituted phenyl derivatives and processes for their preparation|
    GB9412573D0|1994-06-22|1994-08-10|Celltech Ltd|Chemical compounds|
    GB9412571D0|1994-06-22|1994-08-10|Celltech Ltd|Chemical compounds|
    GB9412672D0|1994-06-23|1994-08-10|Celltech Ltd|Chemical compounds|
    IL117090A|1995-02-10|2000-07-26|Schering Ag|Pharmaceutical compositions containing oxazolidinone derivatives|
    DE19540475A1|1995-10-20|1997-04-24|Schering Ag|Chiral methylphenyloxazolidinones|
    GB9523675D0|1995-11-20|1996-01-24|Celltech Therapeutics Ltd|Chemical compounds|
    GB9526246D0|1995-12-21|1996-02-21|Celltech Therapeutics Ltd|Chemical compounds|
    GB9526243D0|1995-12-21|1996-02-21|Celltech Therapeutics Ltd|Chemical compounds|
    GB9526245D0|1995-12-21|1996-02-21|Celltech Therapeutics Ltd|Chemical compounds|
    GB9608435D0|1996-04-24|1996-06-26|Celltech Therapeutics Ltd|Chemical compounds|
    GB9619284D0|1996-09-16|1996-10-30|Celltech Therapeutics Ltd|Chemical compounds|
    GB9622363D0|1996-10-28|1997-01-08|Celltech Therapeutics Ltd|Chemical compounds|
    GB9625184D0|1996-12-04|1997-01-22|Celltech Therapeutics Ltd|Chemical compounds|
    US6057329A|1996-12-23|2000-05-02|Celltech Therapeutics Limited|Fused polycyclic 2-aminopyrimidine derivatives|
    GB9705361D0|1997-03-14|1997-04-30|Celltech Therapeutics Ltd|Chemical compounds|
    GB9713087D0|1997-06-20|1997-08-27|Celltech Therapeutics Ltd|Chemical compounds|
    GB9914258D0|1999-06-18|1999-08-18|Celltech Therapeutics Ltd|Chemical compounds|
    GB9924862D0|1999-10-20|1999-12-22|Celltech Therapeutics Ltd|Chemical compounds|
    CN100480242C|2001-05-29|2009-04-22|舍林股份公司|CDK-inhibitory pyrimidines, and production and use thereof as pharmaceutical agents|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19752541855|DE2541855A1|1975-09-18|1975-09-18|4--2-PYRROLIDONE II|
    [返回顶部]