• 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 N- (3-tri-optor-methylphenyl) -N-propargylpiperazine of the formula rV V-CHo-C W in the form of its acid addition salts, characterized in that K- (3-trifluorophenyl) piperazine is reacted with the compound General formula HC With - CHj - X, where X is a halogen atom or a lower alkylsulfonyloxy group, followed by separation of the target product in the form of its acid addition salts. i CO to HS from 00 NU 4 ::
    公开号:SU1223844A3
    申请号:SU843706206
    申请日:1984-02-27
    公开日:1986-04-07
    发明作者:Банхольцер Рольф；Мерц Герберт；Штокгаус Клаус；Михаэль Енневейн Ганс
    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 nitrogen-containing cyclic compound K- (3-trifluoromethylphenyl) -Y-propargyl-piperaein of formula (1)
    (one)
    /
    N-CHo-C CH
    in the form of its acid addition salts, which have an analgesic effect.
    The purpose of the invention is to obtain a new anesthetic with improved properties.
    Example 1. 3.2 g (0.012 mol of N- (3-trifluoromethyl-1-yl) -piperazine as hydrochloride a, 0.9 g (0.012 mol) of propargyl chloride, and 2.5 g (0.024 mol of sodium carbonate in 50 ml of absolute acetonitrile at stirring heated to 60 C.
    Another .0.34 g (0.0046 mol) of propargyl chloride and 0.5 g (0.0046 mol) of sodium carbonate are added over 15 hours.
    The inorganic salts are removed by suction and the reaction solution is evaporated under reduced pressure. The residue after distillation is dissolved in toluene and the product is extracted with a calculated amount of dilute hydrochloric acid. The aqueous phase is alkalinized with soda and the base is extracted with ether. After drying with sodium sulfate, the solution is evaporated under reduced pressure and the resulting base is converted into hydrochloride.
    White crystals of acetonitrile, mp, 218-219 ° C (decomposition). The yield of 2.7 g (73.8% of theoretical).
    The original piperazine was prepared as follows.
    71.4 g (0.4 mol) of bis- (2-chloroethyl) -amine hydrochloride and 64.4 g (0.4 mol) of 3-trifluoromethylaniline are suspended in 500 nm -butanol and heated to reflux. Bicarbonate is added due to the acidic reaction.
    sodium as a buffer, the water thus formed is azeotropically removed. This procedure is repeated twice after 24 hours with the addition of g (0.08 mol) of 3-trifluoromethylphenylaniline.
    Upon completion of the reaction, the suspension is cooled to 10 ° C, the crystals are aspirated off and the P-butanol is distilled off under reduced pressure. The crystals and distillation residue are dissolved in water and extracted with ether. The aqueous phase is alkalinized with sodium carbonate and extracted with ether. After drying with sodium sulfate under reduced pressure, evaporated and the remaining base is converted to hydrochloride.
    White crystals of ethanol, so pl. 236-237 C (decomposition). Yield 65.2 g (61.1% of theoretical).
    Example 2. 3.2 g (P, 012 mol) of K- (3-trifluoromethylphenyl) -piperazine hydrochloride and 1.67 g (0.014 mol) of pro-pargyl bromide is subjected to stirring with 2.7 g (0.026 mol) of carbonate. MP of absolute acetonitrile at 50 ° C for 20 hours. Then, it is processed as in Example 1 and the base is converted to hydrobromide, m.p. 212 C. (decomposition). Yield 71.5%.
    Example 3. Example 2 is repeated, with the difference that pro-pargyl methanesulfonate is used. The base obtained in this way is transferred to the methanesulfonate, m.p. 197 C (decomposition). Yield 71.8%.
    Analogously to example 1, receive:
    hydrobromide .M- (3-trifluoromethylphenyl) -N-propargylpiperazine, etc. 212 C (decomposition) 5 yield 73.1%;
    fumarate N- (3-trifluoromethylphenyl) - N-propargylpiperazine, m.p. (decomposition), yield 73.5%.
    The pharmacological data given in the table confirm the valuable properties of M- (3-trifluoromethylphenyl) -M propargylpiperazine compared to the known anesthetic with novalgin.
    N- (3-trifluoromethyl-phenyl) -M-propargyl According to Vriting, According to Gait. With rabbit dental pulp.
    Editor N. Dumbass
    Compiled by Y. Belousov
    Tehred I. Veres Proofreader V. But ha
    1729/62 Circulation 379Subscription
    VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., d. 4/5
    Branch P1P Patent, Uzhgorod, st. Project, 4
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING Ν- (3-ΤΡΗΦΤΟΡMETHYLPHENYL) -Y'-PROPARGYLPIPERAZINE IN THE FORM OF ITS ACID-ADDITIVE SALTS (57) Method for the preparation of Ν- (3-τρπφτορmethylphenyl) -Ν ζ -parzaparzene
    CF 3
    CH 2 —C = CH in the form of its acid addition salts, characterized in that Ν- (3-trifluorophenyl) piperazine is reacted with a compound of the general formula
    HC = C - CH 2 - X, where X is a halogen atom or lower alkylsulfonyloxy group, followed by isolation of the target product in the form of its acid additive salts.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1005655A3|1983-03-15|Process for producing 3-aryloxy-3-phenyl-propyl amines or their salts
    JPWO2005097738A1|2008-02-28|New sulfonamide derivatives
    SU416945A3|1974-02-25|METHOD FOR OBTAINING RACEMIC OR OPTICALLY ACTIVE DERIVATIVES OF PIPERAZINE
    EA019329B1|2014-02-28|Process for the preparation of piperazine compounds and hydrochloride salts thereof
    SU1223844A3|1986-04-07|Method of producing n-|-nъ-propargylpiperazine in form of its acid-additive salts
    IE61843B1|1994-11-30|N-aminobutyl-N-phenylarylamide derivatives, their preparation and their application in therapy
    SU402215A1|METHOD OF OBTAINING DERIVATIVES N-AMIHOALKYLAPILYLIMIHOIMIDAZOLIYHOB-212
    US5010095A|1991-04-23|N-|-'-|alkyl)guanidine
    US5244894A|1993-09-14|2-aminopyrimidine-4-carboxamide derivatives, their preparation and their use in therapeutics
    NO20071253L|2007-05-15|Process for the synthesis of C-2, C-3 substituted N-alkylated indoles useful as CPLA2 inhibitors.
    IE56652B1|1991-10-23|Antihypertensive n-piperazinylalkanoylanilides
    US4158013A|1979-06-12|N-Cyano-N'-alkynyl-N"-2-mercaptoethylguanidines
    HU197720B|1989-05-29|Process for production of derivatives of 2-acyl-oxi-prophil-amin and medical preparatives containing them as active substance
    SU497767A3|1975-12-30|The method of producing alkanolamines
    US3898230A|1975-08-05|Sydnone imine compounds
    EP0453731A2|1991-10-30|Improved process for the synthesis of N-3-|phenyl-4-|-2-pyrimidinamines
    RU2440999C2|2012-01-27|Methods and intermediate compounds for preparing imatinib, optionally radiolabelled
    SU493067A3|1975-11-25|The method of obtaining phenylimidazolidinone
    SU420176A3|1974-03-15|
    PT1487810E|2010-04-27|4-|-1-piperazinyl derivatives
    IE921319A1|1992-11-04|2-aminopyrimidine-4-carboxamide derivatives, their¹preparation and their application in therapy
    CS241064B2|1986-03-13|Method of n-substituted nicotinamide's 1-oxide and its salts production
    US3330825A|1967-07-11|Thiophene compounds
    US4029786A|1977-06-14|Morpholine derivatives for treating depression
    JP4173363B2|2008-10-29| acetamide as a novel neurokinin antagonist
    同族专利:
    公开号 | 公开日
    PT78155B|1986-07-17|
    ES8603444A1|1985-12-16|
    DE3460733D1|1986-10-23|
    GR79822B|1984-10-31|
    ZA841418B|1985-11-27|
    US4699910A|1987-10-13|
    DK102084D0|1984-02-24|
    ES8504754A1|1985-04-16|
    DK158729C|1990-11-19|
    NO840732L|1984-08-29|
    DK158729B|1990-07-09|
    FI77658C|1989-04-10|
    FI77658B|1988-12-30|
    EP0117531A1|1984-09-05|
    NO158803C|1988-11-09|
    ES530073A0|1985-04-16|
    PL246418A1|1985-07-02|
    FI840743A0|1984-02-23|
    IL71068D0|1984-05-31|
    GB2135997B|1986-02-19|
    IE56938B1|1992-02-12|
    NZ207289A|1986-07-11|
    GB8405113D0|1984-04-04|
    ES536411A0|1985-10-16|
    CS127484A2|1985-06-13|
    EP0117531B1|1986-09-17|
    IL71068A|1988-05-31|
    PT78155A|1984-03-01|
    JPH056545B2|1993-01-26|
    ES536416A0|1985-12-16|
    AU2508584A|1984-09-06|
    ES536415A0|1985-12-16|
    GB2135997A|1984-09-12|
    CS240997B2|1986-03-13|
    AT22289T|1986-10-15|
    ES8601174A1|1985-10-16|
    DD218096A5|1985-01-30|
    CA1240327A|1988-08-09|
    ES8603447A1|1985-12-16|
    PH21982A|1988-05-02|
    HU190546B|1986-09-29|
    ES8603446A1|1985-12-16|
    KR910005413B1|1991-07-29|
    FI840743A|1984-08-29|
    ES8601173A1|1985-10-16|
    AU562643B2|1987-06-18|
    IE840460L|1984-08-28|
    PL141275B1|1987-07-31|
    ES8603445A1|1985-12-16|
    DK102084A|1984-08-29|
    ES536413A0|1985-12-16|
    ES536412A0|1985-10-16|
    DE3306964A1|1984-09-06|
    KR840007875A|1984-12-11|
    ES536414A0|1985-12-16|
    JPS59210074A|1984-11-28|
    NO158803B|1988-07-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2993899A|1958-03-31|1961-07-25|Miles Lab|Acetylenically unsaturated piperazine derivatives|
    NL6607959A|1965-06-10|1966-12-12|
    DE1545561A1|1965-08-23|1969-12-11|Acraf|Process for the preparation of pharmacologically active N, N-disubstituted 1-aryl-3-aminopropines|
    FR2187311B1|1972-06-02|1975-06-20|Bouchara Emile|
    GB1560271A|1977-01-14|1980-02-06|Joullie International Sa|Therapeutically useful m-trifluoromethylphenylpiperazine derivatives|
    US4180574A|1978-12-26|1979-12-25|Abbott Laboratories|Certain ovicidal piperazines|
    US4518712A|1980-06-30|1985-05-21|Taiho Pharmaceutical Company Limited|Piperazine derivative and analgesic composition containing the same|JPH03176457A|1989-12-04|1991-07-31|Nippon Paint Co Ltd|Novel propargyl compound, its production and coating material containing the same compound|
    JPH05255089A|1991-12-18|1993-10-05|Sanwa Kagaku Kenkyusho Co Ltd|Antiviral agent|
    US5661163A|1995-06-07|1997-08-26|Merck & Co., Inc.|Alpha-1a adrenergic receptor antagonists|
    USRE46117E1|1999-12-22|2016-08-23|Teva Pharmaceuticals International Gmbh|Modulators of dopamine neurotransmission|
    ES2776678T3|2012-04-04|2020-07-31|Prilenia Neurotherapeutics Ltd|Pharmaceutical compositions for combination therapy|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19833306964|DE3306964A1|1983-02-28|1983-02-28|NEW N-ARYLPIPERAZINE AND METHOD FOR THE PRODUCTION THEREOF|
    [返回顶部]