• 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 invension provides compounds of formula I, I wherein R1 is, for example, hydrogen or alkanoyl of 1 to 20 carbon atoms; R2 is, for example, hydrogen, hydroxy, alkanoyl of 1 to 20 carbon atoms, CF3SO2NH or CC13SO2NH; R3 is hydrogen or, when R2 is chlorine, R3 may also be chlorine; R4 is, for example, hydrogen, alkyl of 1 to 4 carbon atoms or cycloalkyl of 3 to 8 carbon atoms; and R6 is, for example, hydrogen, alkyl of 1 to 4 carbon atoms or, together with R5, a -(CH2)4-, -(CH2)5 or (CH2)6-group, which compounds possess pharmacological activity, for example in she treatment of cardiac diseases and Parkinson's disease.
    公开号:SU927110A3
    申请号:SU772549950
    申请日:1977-12-06
    公开日:1982-05-07
    发明作者:Плесс Янош；Зайлер Макс-Петер
    申请人:Сандос Аг(Фирма)；
    IPC主号:
    专利说明:

    in the following cases: if HE is in position 6 and RI is hydrogen, then NR4 RS can mean NN2; if it is in position 5 H.Ri hydrogen, then NR4R5 is NHj or NHCHs, or their salts.
    The compounds of formula 1 can exist as enantiomers or as racemates and can be used as pharmacologically active compounds.
    The known method, based on the reaction of your alkoxy or benzyloxy protective tinder using diluted acids 1.
    The aim of the invention is to expand the range of agents acting on a living organism.
    The goal is achieved by the fact that according to the method for producing 2-amino-1,2,3,4-tetrahydronaphthalene derivatives or their salts of formula 1 in a compound of the general formula
    "2h
    (and)
    where R is C1-C4-alkyl or benzyl, RI has the same meanings as P and may additionally mean C-C4-alkoxy or benzyloxy, alkoxy or benzyloxy is converted to free hydroxyl using hydroiodic, hydrobromic, hydrochloric acids at 0 -100 ° C or boron tribromide at 0--50 ° C, or by catalytic hydrogenation in the presence of a platinum group catalyst, followed by allocation of the desired product as a free compound or salt.
    Example. 2-amino-1,2,3,4-tetrahydro-8-hydroxy-2-oximet yl naphthalene.
    2-Amino-2-carboxy-1,2,3,4-tetrahydro-8-metoxyn-naphthalene.
    To a suspension of 50 g of 8-methoxy-2-tetralone in 350 ml of isopropanol was added 28 g of potassium cyanide along with 76.5 g of ammonium carbonate. The mixture is moved at 60 ° C for
    20 hours, cooled to room temperature, mixed with 400 ml of water and left to stand at 4 ° C for crystallization, 8-methoxy-2-spirohydroantointetratraline crystallized out, mp. 216-217 ° C. Suspension
    21g of 8-methoxy-2-spirohydantointetrathrin in 130 ml of propylene glycol is mixed with 42 ml of a 407% aqueous solution of sodium hydroxide and heated for 24 hours with stirring to 190 ° C. The cooled solution is decolorized with activated carbon, made up of concentrated hydrochloric acid to The pH of the precipitate is filtered off and the mother liquor is adjusted to pH 5.5 by addition of sodium carbonate / acetic acid buffer solution. After isolation and drying, the target compound crystallized out of this solution; mp. 228230 S.
    2-Amino-1,2,3,4-tetrahydro-8-methoxy-2-hydroxymethylnaphthalene.
    A suspension of 14.5 g of 2-amino-2-carboxy-1,2,3,
    0 4-tetrahydro-8-methoxynaphthalene in 400 ml of tetrahydrofuran with stirring (apparatus is in a stream of nitrogen) is added dropwise to 525 ml of a 1 M solution of diborane in tetrahydrofuran. The reaction solution is boiled under reflux for 12 hours, immediately cooled to room temperature, mixed with 400 ml of methanol and evaporated. The residue is mixed with 300 ml of 2 n. The ethanolic hydrogen chloride solution is heated under reflux for 2 hours, the cooled solution is evaporated and the precipitate is shaken immediately afterwards with 1N. sodium hydroxide / methylene chloride. The organic phase is evaporated until dry; the residue is chromatographed on snigel with a mixture of 10% ammonia / methylene chloride and methanol (9: 1). The target compound, which is isolated as an oil, is dissolved in ethanol / ether (1: 1) for conversion to its hydrochloride, mixed with one equivalent of 4N. solution of ethereal hydrogen chloride and allowed to stand at 4 ° C for crystallization, thus obtaining the hydrochloride of the target compound with m.p. 153-154 ° C.
    2-amino-1,2,3,4-tetrahydro-8-hydroxy-2-hydroxymethylnaphthalene.
    5 g of 2-amino-1,2,3,4-tetrahydro-8-methoxy-2-hydroxymethyl-naphthalene hydrochloride are suspended in 100 ml of methylene chloride and mixed
    with 6.8 ml of boron tribromide. Reaction mixture p,
     stirred for 4 h at room
    temperature is then mixed directly thereafter with 10 ml of methanol, and the reaction mixture is evaporated. The residue was evaporated in 50 ml portions of ethanol each time from the baufir, shaken with a 1N mixture. an aqueous solution of potassium carbonate and a mixture of methclen chloride / isopropanol (2: 1) and the residue of the dried, distilled organic phase is chromatographed on silica gel with a mixture of 10% ammonia, methylene chloride and methanol (7: 3). The desired compound obtained as a foam is dissolved in ethanol, mixed with ethereal hydrogen chloride solution and left to stand at -10 ° C.
    5 thus obtaining the target compound in the form of its hydrochloride with so pl. 191-193 ° C.
    权利要求:
    Claims (1)
    [1]
    PRI mme R 2. 2-amino-1,2,3,4-tetrahydro-6-acetoxy-2-acetoxymethyl-naphthalene. 5 Suspension of hydrobromide 1 g of 2-amino-1,2,3,4-tetrahydro-6-hydroxy-2-hydroxymethyl afthalin in 12 ml of trifluoroacetic acid is mixed with 1 ml of acetyl chloride, after which everything immediately goes into solution when the gas is removed. Then it is stirred for another 1.5 hours at room temperature and immediately thereafter lyophilized. The residue is triturated in 50 ml of ether, sucked off and washed with 50 ml of ether. PRI me R 3. Hydrochloride N- (2- (3,4-dimethoxyphenyl) -ethyl) -2-methylamino-1,2,3,4-tetrahydro-6-hydroxynaphthalene. 4.6 g of N- (2- (3,4-dimethoxiphenyl) -acetyl) 2-methylamino-1, 2,3,4-tetra-hydrohydro-6-hydroxy-naphthalene are suspended under stirring in 70 ml of tetragndrofuran, added drop 65 ml of 1 M solution of diborane in tetragvdrofur not to this solution and the reaction mixture is stirred for 3 hours at room temperature, then immediately stirred at 60 ° for 3 hours. The cooled reaction solution is mixed with an excess of 4N. hydrochloric acid. After that, it is evaporated to dryness, the residue is mixed with methanol, evaporated, and this operation is repeated several times. The residue obtained in this way is chromatographed on silica gel with a mixture of methyl chloride and methanol (9: 1). The title compound thus separated is dissolved in methanol, mixed with methanolic hydrochloric acid and evaporated to dryness. The residue is dissolved in 50 ml of isopropanol and the desired compound is precipitated as its hydrochloride by adding 300 ml of ether (m.p. above 95 ° C). M-p- (3,4-dimethoxyphenyl) acetyl) -2-methylamino-1,2,3,4-tetrahydro-6-hydroxynaphthalene, used as the starting product, is obtained by reacting 6-hydroxy-2-metsh-amino 1, 2,3,4-tetrahydronaphthalene with hydroxy succinimido ester of 3,4-dimethoxyphenyl-acetic acid in dimethylformamide at room temperature. By analogy with the examples given and with the use of the corresponding starting compounds, other compounds of the formula I are prepared. Formula of the invention
    where RI is hydrogen, hydroxy, halogen, Ci-C4-alkyl, C1-C4-alkylsulfonylamino,
    where R is Cj-C4-alkyl or benzyl, RI has the same meanings as R and additionally CFjSOiNH, CCtjSOjNH, CHjOH, CH, -O-CO- (CHj) n-R6 or CHj-O-COR7, where RV - hydrogen or Ci-Ci9 alkyl and n 0-5. R is a group of the general formula DO3 Y and UG independently of one another — hydrogen, halogen, C 1 –C 4 -alkyl or C 1 –C 4 alkoxy, or y and V 2 With the adjacent C-atom together denote methylenedioxy; hydrogen, even when RJ is chlorine, is also chlorine; hydrogen, CHjOH, CH-O-CO-R, or CHj-0-CO- (CHi) n - hydrogen, C, -C4-alkyl, C-Cv-cycloalkyl or (CHj) n - Re. where Rg is a group of the general formula: where Ouse, U4, U5 are independently each other, hydrogen, halogen, Ci-C4-kil, Cj-C4-alkoxy-OH, OH, or Uz and U4 At the adjacent C-atom, they are together methylenedioxy. hydrogen or C1-C4-alkyl or R and RS together represent (CH2) 4, (CHj) s or (CH2) b, and if RJ and RS are free or acylated CHjOH, they are identical, provided that in the case of Yaz is hydrogen and RJ is hydrogen, OH or alkyl, NR4Rs cannot denote an amino group that is free or substituted only with alkyl or benzyl or cannot denote a hetero ring, except for the following cases: if it is in position 6 and R, is hydrogen, then NR4Rs can mean NHj; if OH is in position 5 and RI is hydrogen, then NR4R5 NHj or NHCHs, which is characterized by the general formula II
    1 9271108
    may mean C1-C4-alkoxy or benzyl-Priority on the basis of:
    C, alkoxy or benzyloxy is converted to its December 12, 1997 at RI — hydrogen or OH; Rj
    hydroxyl lean with hydroiodo; BG - R4 and R; hydrogen
    native, hydrobromic, hydrochloride- or C1-C4-alkyl.
    hydrochloric acid at O-100 ° C or boron tribromide 05.01.77 with RI-RS is hydrogen.
    when, or by kataditicheski gidri-Sources of information,
    in the presence of a catalyst, the platinum is taken into account in the examination
    howling troupe with the subsequent selection of cele-i. Greenstein, J., Winitz, M. Chemistry of the amine product in the form of a free compound of acids and peptides. World, 1965, p. 757,
    or salt.
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    同族专利:
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    引用文献:
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    WO1982004042A1|1981-05-11|1982-11-25|Folke Lars Erik Arvidsson|Therapeutically useful tetralin derivatives iii,processes for preparation and pharmaceutical preparations for such compounds|
    US4454154A|1981-06-23|1984-06-12|American Hospital Supply Corporation|Method for treating glaucoma by the topical administration of selectively metabolized beta-blocking agents|
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    US4743618A|1983-01-03|1988-05-10|Nelson Research & Development Co.|Substituted 2-aminotetralins|
    US4564628A|1983-01-03|1986-01-14|Nelson Research & Development Co.|Substituted 2-aminotetralins|
    US5177112A|1983-01-03|1993-01-05|Whitby Research, Inc.|Substituted 2-aminotetralins|
    US4657925A|1984-08-13|1987-04-14|Nelson Research & Development Co.|Method and compositions for reducing the intraocular pressure of mammals|
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    US5214156A|1988-03-25|1993-05-25|The Upjohn Company|Therapeutically useful tetralin derivatives|
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    JP2931986B2|1989-02-17|1999-08-09|武田薬品工業株式会社|Aralkylamine derivatives|
    SE8901889D0|1989-05-26|1989-05-26|Astra Ab|NOVEL 8-SUBSTITUTED-2-AMINOTETRALINES|
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    ES2205227T3|1996-05-31|2004-05-01|PHARMACIA & UPJOHN COMPANY|ARIL-REPLACED CYCLINE AMINES AS DOPAMINE D3 'SELECTIVE LINKS.|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    CH1535376|1976-12-07|
    CH8277|1977-01-05|
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