• 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 provides novel 1-substituted-5-hydroxymethyl-2-mercapto-imidazoles of the formula wherein R is pyridylmethyl, alkyl of 1 to 4 carbon atoms, or a radical of formula: R1 is hydrogen or halogen and n is 1-3. These compounds are prepared by reacting together dihydroxyacetone dimer, the amine R-NH2, and potassium thiocyanate. The compounds of formula (I) are useful as starting materials in the preparation of known therapeutically valuable imidazole derivatives, by removing the mercapto group, oxidizing the alcohol group to an aldehyde group and condensing the aldehyde with an appropriate phenyl or phenylalkyl magnesium halide.
    公开号:SU1301313A3
    申请号:SU843801008
    申请日:1984-10-17
    公开日:1987-03-30
    发明作者:С.Л. Пархи Сеппо
    申请人:Фармос-Ихтюмя Ой (Фирма)；
    IPC主号:
    专利说明:

    113
    The invention relates to a process for the preparation of new substituted 2-mercaptoimidazoles, which can be used as intermediates for the synthesis of biologically active substances.
    The purpose of the invention is the synthesis of new compounds that are intermediate for the synthesis of compounds with valuable properties.
    Example 1, 1-Benzyl-2-mercapto-5-hydroxymethyl-imidazole.
    N-butanol (50 g), glacial acetic acid (25 g), dioxyacetone dimer (21.0, g), potassium thiacyanate (34.1 g) and benzylamine (28.0 g) are mixed and stirred at room temperature in for 50 hours, and the desired product is separated by filtration,
    13 C NMR (flKCO-d6, TMS); 46.35; 53.22; 112.46; 112.61; 126.69; 127.02; 128.20; 130.20; 136.92; 162.53,
    A light brown product is obtained (35.0 g, 68.2%), t, melt. 229- 231 ° C,
    Using the same procedure, the following products can be obtained:
    1 (4-Chlorobenzyl) -2-mercapto-5-hydroxymethyl-imidazole, m.p. 217-222 С,
    1- (2-Phenylethyl) -mercapto-5-hydroxymethyl-imidazole. t, melt, 202-208 С,
    1- (2-Pyridylmethyl) -2-mercapto-5-hydroxymethyl-imidazole, t, melt, 181-185 ° C,
    1-Ethyl-2-mercapto-5-hydroxymethyl imidazole, t, melt, (decomposition) 175250 ° C.
    Example 2, 4- (2,3-dimethylbenzyl) -imidazole hydrochloride,
    I-Benzyl-2-mercapto-5-hydroxymethyl-imidazole (7.5 g) is added in small portions to a mixture of wax (18 ml) and concentrated nitric acid (7.5 g) at 35 ° C. Then the mixture is stirred for 3 h and the pH of the reaction mixture is provided at a level of 9-10 with sodium hydroxide, the result is 1-benzyl-5-ocK
    K X shda
    R
    DHissOa.
    2) NaOH
    MpOg
    N, -A dloxan
     sdda
    R
    five
    0
    five
    0
    five
    0
    50
    32
    Simethyl-imidazole (3.8 g, 60%), t, melt, 131-135 0,
    1-Benzyl-5-hydroxymethyl-imidazole (4.5 g), activated MpO (8.5 g) and dioxane (25 ml) are mixed. The mixture is then stirred at 90 ° C for 6 hours, filtered and evaporated to dryness. The product (1-benzyl-5-carboxaldehyde) crystallizes from acetone as white crystals. The output of 3.58 g (80%), t, melt, 52-54 ° C,
    2,3-Dimethylphenylmagnesium bromide (40 g), obtained in a known manner, in 500 ml of tetrahydrofuran is added dropwise to a solution in tetrahydrofuran 1-benzyl-5-carboxaldehyde (12 g). The reaction mixture is stirred for 5 hours and poured into ice-water (170 ml). Then the mixture is stirred and filtered. A white NCE-salt of 1-benzyl-5-fti- (2,3-dimethylphenyl) oxymethyl-imidazole is thus obtained (18.2 g, 85%). The product can be subjected to recrystallization, for example, from isopropanol.
    1-Benzyl-5-ci - (2,3-dimethylphenyl) oxymethyl-imidazole hydrochloride (17 g), 1 N, a solution of HC8 (190 ml) and a Pd / C catalyst are mixed. The mixture is then subjected to hydrogenation using a known method at normal pressure at 60 ° C until hydrogen is already consumed. The catalyst is separated by filtration, and the filtrate is alkalinized with sodium hydroxide. The product can be converted into the hydrochloride salt by reacting with KSV-isopropanol in ethyl acetate, t, melt, 154-159 ° C, Yield 8 g (70%),
    The value of the proposed compounds is that after the mercapto group is removed, the alcohol is oxidized, and the resulting aldehyde is converted to 4 (5) -monosubstituted imidazole in 70% yield. The use of the inventive compound of the formula I in the process for the preparation of said monosubstituted imidazoles is carried out according to the following scheme:
    MpOg
     dloxan
    TJ {jpCHO
    N R

    14 OH
    (/ 7у
    sn sn
    1 N
      / 7у
    sn sn
    1 N
    There is a known method for preparing 4 (5) -imidazoles, which can be represented by a scheme;
    N ... J.
    H "GH
    -N OH
    fg
    (6n- (, b
    to
    H
    N N
    fg
    ,
    N N
    Z Ato or SOOCH.
    This method is carried out only in laboratory conditions with a low yield, while the use of 2-mercapto-imidazole as a starting material for the preparation of therapeutically active 4 (5) -imidazole derivatives leads to a high yield of products, which entails a large economic effect. Effect.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining the substituted 2-mercapto-imidazoles of the general formula
    N
    Chh
    N SNGON
    at
    Editor M.Petrova Order 1163/58
    Compiled by G.Zhukova Tehred V.Kadar
    Proofreader L.P.
    Circulation 372Subscribe
    VNIIPI USSR State Committee
    for inventions and discoveries P3035, Moscow, Zh-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, Projecto st., 4
    where R is benzyl, 4-chlorobenzyl, 2-phenylethyl, 2-pyridylmethyl or
    ethyl group
    characterized in that the dioxyacetone dimer of the formula
    About CHjOH
    v
    HOCH2 about
    are reacted with potassium thiocyanate of the formula
    KSCN
    and a primary amine of the formula RNHj,
    where R- is as defined, in a lower alcohol in the presence of an acid at room temperature.
    Proofreader L. Patay
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1301313A3|1987-03-30|Method for producing substituted 2-mercapto-imidazoles
    CA1340549C|1999-05-18|Method of preparing sphingosine derivatives
    SU541431A3|1976-12-30|The method of obtaining derivatives of pyrazolyloxyacetic acid or their salts
    DE3336225C2|1993-06-24|
    SU1318156A3|1987-06-15|Method for producing 1-benzylazetidine-3-ol
    US4668798A|1987-05-26|Process for preparing pyrrolidine derivatives
    US4560764A|1985-12-24|Synthesis of an imidazolyl isothiourea
    US2872454A|1959-02-03|Spiro-hydantoins from x-chloro-
    CA2016500C|2000-11-28|Process for producing beta-lactamase inhibitor
    US4348528A|1982-09-07|Process for the preparation of 1-phenyl-3-carbamoyl-5-pyrazolones
    US4188489A|1980-02-12|Process for the production of 3-substituted amino-5-pyrazolones
    US4468518A|1984-08-28|Imidazole guanidine compounds and method of making same
    US4290971A|1981-09-22|Method of preparing 2-|-imidazolines-|
    JP2578797B2|1997-02-05|Method for producing N- | formamides
    FI69302B|1985-09-30|1-substituted-5-hydroxymethyl-2-mercapto-IMIDAZOLER
    DE2618756A1|1977-11-03|IMIDAZOLE COMPOUNDS AND PROCESS FOR THEIR PRODUCTION
    US3275649A|1966-09-27|Process for the preparation of
    CH630371A5|1982-06-15|METHOD FOR PRODUCING NEW MERCAPTOTETRAZOLE COMPOUNDS.
    CA1120493A|1982-03-23|Process for producing 4'-|phenyltrans-4-aminomethylcyclohexanecarboxylate or theacid-addition salts thereof and intermediates forproducing the same
    CA1248960A|1989-01-17|Substituted 2-mercapto-imidazoles
    SU509223A3|1976-03-30|The method of obtaining derivatives of 1-carbamoylimidazole
    US4520201A|1985-05-28|Synthesis of cimetidine and analogs thereof
    DE3125990A1|1982-02-04|Process for preparing imidazole derivatives
    SK19993A3|1993-10-06|Process for preparing 1-|-methyl-propionyl)- -l-proline
    RU1796619C|1993-02-23|N-phenacetyl-n-ethyldithiocarbamine acid as intermediate product in thiazolium salts synthesis and method for thiazolium salts production
    同族专利:
    公开号 | 公开日
    HU191960B|1987-04-28|
    DK471384D0|1984-10-02|
    NO159167C|1988-12-07|
    HUT35649A|1985-07-29|
    DD236730A1|1986-06-18|
    ES8507507A1|1985-09-01|
    DK174201B1|2002-09-16|
    UA5972A1|1994-12-29|
    IE842652L|1985-04-18|
    NZ209896A|1987-02-20|
    US4584383A|1986-04-22|
    DK471384A|1985-04-19|
    NO159167B|1988-08-29|
    DE3468869D1|1988-02-25|
    AU3426384A|1985-04-26|
    FI833794A0|1983-10-18|
    ES536186A0|1985-09-01|
    EP0146228B1|1988-01-20|
    IL73255A|1988-11-30|
    JPS60149568A|1985-08-07|
    AU566437B2|1987-10-22|
    AT32064T|1988-02-15|
    IE57591B1|1993-01-13|
    EP0146228A1|1985-06-26|
    ZA848112B|1985-06-26|
    IL73255D0|1985-01-31|
    NO844139L|1985-04-19|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2541924A|1948-09-17|1951-02-13|Lilly Co Eli|Synthesis of substituted imidazoles|
    AU518569B2|1979-08-07|1981-10-08|Farmos-Yhtyma Oy|4-benzyl- and 4-benzoyl imidazole derivatives|
    GB2092569B|1981-02-05|1984-09-19|Farmos Oy|Substituted imidazole derivatives and their preparation and use|US4634711A|1985-08-02|1987-01-06|Smithkline Beckman Corporation|Pyridylalkyl imidazole-2-thiols|
    US5210079A|1988-01-07|1993-05-11|E. I. Du Pont De Nemours And Company|Treatment of chronic renal failure with imidazole angiotensin-II receptor antagonists|
    US5354867A|1988-12-06|1994-10-11|E. I. Du Pont De Nemours And Company|Angiotensin II receptor blocking imidazoles|
    US5138069A|1986-07-11|1992-08-11|E. I. Du Pont De Nemours And Company|Angiotensin II receptor blocking imidazoles|
    CA1338238C|1988-01-07|1996-04-09|David John Carini|Angiotensin ii receptor blocking imidazoles and combinations thereof with diuretics and nsaids|
    FI91754C|1986-12-02|1994-08-10|Tanabe Seiyaku Co|An analogous method for preparing an imidazole derivative useful as a medicament|
    US4882348A|1987-12-29|1989-11-21|Smithkline Beckman Corporation|2-imidazoles as dopamine-β-hydroxylase inhibitors|
    US4880804A|1988-01-07|1989-11-14|E. I. Du Pont De Nemours And Company|Angiotensin II receptor blocking benzimidazoles|
    EP0479892A1|1989-06-30|1992-04-15|E.I. Du Pont De Nemours And Company|Fused-ring aryl substituted imidazoles|
    US5073566A|1989-11-30|1991-12-17|Eli Lilly And Company|Angiotensin ii antagonist 1,3-imidazoles and use thereas|
    US5332820A|1991-05-20|1994-07-26|E. I. Du Pont De Nemours And Company|Dibenzobicyclo octane angiotensin II antagonists|
    US5612360A|1992-06-03|1997-03-18|Eli Lilly And Company|Angiotensin II antagonists|
    US5401851A|1992-06-03|1995-03-28|Eli Lilly And Company|Angiotensin II antagonists|
    IT1295405B1|1997-09-30|1999-05-12|Merck Sharp & Dohme Italia S P|USE OF AN ANGIOTENSIN II RECEPTORAL ANTAGONIST FOR DRUG PREPARATION TO INCREASE THE SURVIVAL RATE OF|
    KR100567183B1|1997-11-14|2006-06-13|론자 아게|How to prepare formyl imidazole|
    KR100388788B1|1999-09-06|2003-06-25|주식회사 엘지생명과학|A novel process for preparing 1-substituted-5-hydroxymethyl imidazole|
    CA2382861A1|1999-09-06|2001-03-15|Sung-Kee Kim|Process for preparing a 1-substituted 5-hydroxymethyl imidazole|
    US6620939B2|2001-09-18|2003-09-16|General Electric Company|Method for producing bisphenol catalysts and bisphenols|
    US7112702B2|2002-12-12|2006-09-26|General Electric Company|Process for the synthesis of bisphenol|
    FI116292B|2003-01-08|2005-10-31|Juvantia Pharma Ltd Oy|Process for the preparation of substituted imidazole derivatives and in the process useful intermediates|
    US7132575B2|2003-07-01|2006-11-07|General Electric Company|Process for the synthesis of bisphenol|
    FI20050391A0|2005-04-15|2005-04-15|Orion Corp|Crystallization method for detomidine hydrochloride|
    CN101747280B|2008-11-28|2011-11-09|上海迪赛诺医药发展有限公司|Method for preparing detomidine and the intermediate thereof|
    WO2020016827A1|2018-07-18|2020-01-23|Clexio Biosciences Ltd.|Purified crystalline detomidine hydrochloride monohydrate, anhydrate and free base with low amounts of iso-detomidine and other impurities by recrystallisation in water|
    EP3782989A1|2019-08-23|2021-02-24|Andreas Sachse|Detomidine hydrochloride monohydrate|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FI833794A|FI833794A0|1983-10-18|1983-10-18|SUBSTITUERADE 2-MERKAPTO-IMIDAZOLER|LV920317A| LV5065A3|1983-10-18|1992-12-17|Method of obtaining substituted 2-mercapto-imidazoles|
    LTRP767A| LT2219B|1983-10-18|1993-07-07|THE DRAFT RECEIPT OF THE 2-MERKAPTO-IMIDAZOLU|
    [返回顶部]