• 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:
    New piperidinopropyl derivatives have a low toxicity and an outstanding vasodilatory action which manifests itself in a sinking of the blood pressure, furthermore, an inhibition of adrenergic 8-receptors has also been observed. The derivatives are of formula (I): (I) wherein R1 and R2, which can be the same or different, are selected from the group consisting of a hydrogen atom, lower alkyl, hydroxy-lower-alkyl, lower alkanoyloxy-lower alkyl and a-CO-Z group, wherein Z is hydroxy, lower alkoxy or an radical, in which R6 and R7, which-can be the same or different, are selected from the group consisting of a hydrogen atom, lower alkyl and hydroxy-lower-alkyl, R3 is a hydrogen atom or an-O-R8 radical, wherein R8 is a hydrogen atom, a lower alkanoyl radical or an aroyl radical which is unsubstituted or substituted by halogen, lower alkyl, lower alkoxy, lower-alkoxycarbonyl, hydroxyl, lower-alkylthio, nitrile, nitro or trifluoromethyl R4 and R5, which can be the same or different, are selected from the group consisting of a hydrogen atom, a halogen atom, hydroxyl, benzyloxy, lower alkyl, lower alkoxy, lower alkylthio, carboxyl, benzyloxy-carbonyl and lower alkoxycarbonyl, X and Y, which can the the same or different, are nitrogen atoms or radicals, wherein R9 is a hydrogen atom or a lower alkyl radical, which is unsubstituted or substituted by an -O-R8 radical, wherein R8 is as defined above, or a -CO-Z group, wherein Z is as defined above, the pharmaceutically acceptable, pharmacologically compatible salts are also useful.
    公开号:SU890975A3
    申请号:SU782675553
    申请日:1978-10-20
    公开日:1981-12-15
    发明作者:Кампе Вольфганг；Фрибе Вальтер-Гунар；Видеманн Фритц；Шпонер Гисберт；Барч Вольфганг；Дитманн Карл
    申请人:Берингер Маннхайм Гмбх (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing new derivatives of aminopropanol of the formula
    in which R ^ and R ^ may be the same or different and mean hydrogen, a lower alkyl group, an oxyalkyl group, a (lower alkanoyl) oxyalkyl group or a -CO-Z group, 15 further on a halogen, lower alkyl, and therefore Z means a hydroxyl group, a lower alkyloxy group or te * 7 group in which R & and R · may be the same or different and mean hydrogen, a lower alkyl group or a hydroxyalkyl group. . 25
    Ra is hydrogen or a group —0 — Rg, wherein Rg is hydrogen, a lower alkanoyl group or an aroyl group, which may be your alkoxy group, alkoxy carbonyl group, hydroxyl group, alkylthio group, nitrile group, nitro group or trifluoromethyl group , R 4 and R 5 may be the same or different and mean hydrogen, halogen, hydroxyl group, benzyloxy group, lower alkyl group, lower alkyloxy group, lower alkylthio group, carboxyl group, benzyloxycarbonyl group or cisch alkyloxycarbonyl group.
    The invention also relates to a method for producing salts of said compounds.
    The compounds of formula I and their salts are pharmacologically active compounds: with minor toxicity, they have pronounced vasodilating properties, which are manifested in lowering blood pressure; in addition, they’re capable of suppressing adrenergic β-receptors.
    Various derivatives of aminopropanols having (¾ -adrenergic blocking activity) are widely described in the literature.
    A known method of producing derivatives of alkanolamine of the General formula /
    where is r - isopropyl, R 2 - carbamoylaminoalkyl, mono- and di-alkylcarbamoyl-fl aminoalkyl, carbamoylaminoalkoxyl, mono- and di-alkylcarbamoylaminoalkyl as well as. -'Hydrogen, halogen, and
    . Nine 3
    I 3
    ΟζϊΓ
    where R ^ -Rg have the indicated meaning, reduced by complex metal hydrides or by catalytic hydrogenation, and cyclized. Target products are isolated in free form or in the form of. Salts. For the preparation of salts, the most suitable acids are hydrochloric, phosphoric, sulfuric, acetic, citric, maleic and benzoic. Target products can be isolated as a racemate or an optically + active antipode.
    Example 1. 2-Methyl-Z-nitro • epoxyphenol.
    10.7 g (0.07 mol) of 2-methyl'-3-nitrophenol is dissolved in 55 ml of epichlorohydrin, 7.9 g of MAOSH (0.14 mol) are added dropwise in 75 ml of ethanol and the mixture is stirred for 16 hours at room temperature. temperature. After removing ί of excess epichlorohydrin in vacuo, the residue is taken up in ether and extracted three times with water. After drying the organic phase over their salts, it consists in the fact that the compound of the formula
    At 2 o <Jh 2 Choh0h 2 nh 2 , the 3 have the indicated meanings, they are reacted with a compound of the formula ZR 1 , where R 1 has the indicated meanings, and 2 'is the reactive ester esterified with hydroxyl group fl].
    The purpose of the invention is the expansion of the range of products that affect a living organism.
    This goal is achieved by a method that is based on the well-known reaction of the formation of a hetero ring during ring closure due to 2 carbon atoms of the side chain of 0-amino (or nitro) phenyl compounds when heated in the presence of a reducing agent : agent £ 2].
    In accordance with the invention, a method for producing derivatives of aminopropanol of the specified formula 1 is described, which consists in the fact that the compounds of the formula
    g masisomer 2. 1- (2-hydroxy-3) -4HaQ $ O ^. and evaporation remains 17 la, which after grinding with propanol and naphtha crystallizes. After suctioning the crystals, G is obtained, '~ _______ ~.
    phenol with so pl. 46-48 C (58% of theory).
    When -phenoxymethyl- (piperidino) -propoxy-: 2-methyl-3-nitrophenol.
    4.2 g (0.02 mol) of the title compound are dissolved in 100 ml of n-butanol and mixed with 3.8 g (0.02 mol) of 4-phenoxymethylpiperidine. After standing overnight at room temperature, the formed crystals are sucked off, washed with a small amount of ligroin and 6.9 g of the target compound are obtained with mp 103-4 104 ° C (86% of theory).
    Example 3. 1- (2-hydroxy-3) -4-phenoxymethyl- (piperidino) propoxy-2-dimethyl-amino-ethylene-3-nitrobenzene.
    8.6 g 2-methyl-3-nitro-epoxy IS
    3.0 g (0.0075 mol) of the indicated compound is dissolved in 20 ml of dimethylformamide, mixed with 1.6 ml * (0.011 mol) of Μ, Ν-dimethylformamide dimethyl acetal and heated for 8 hours while distilling the resulting alcohol to reflux. After evaporation in vacuo, 4.0 g of an oily residue remains.
    Example 4. 4- (2-hydroxy-3) -4-phen-1c oxymethyl-piperidino (-propoxyJ-indole 4.0 g of the crude product is suspended in 150 ml of methanol, mixed with 1.0 g of 10% palladium on charcoal and shaken for 2 hours with hydrogen 19. At the end of hydrogen absorption, the catalyst is filtered off, the solution is evaporated, dissolved in ethyl acetate and benzoate is obtained by adding> the calculated amount of benzoic acid lot. 1.5 g yield ( 39% of theory), mp 145-147 0 С.
    Similarly receive:
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -indole, m.p. 127,129 ° C (as acetate);
    ‘4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy] -2-ethoxycarbonyl-indole, m.p. 170 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperi-EO dino) -propoxyj-2-carbamoyl-indole, m.p. 182 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -2-dimethylaminocarbonyl-indole, m.p. 178 ° C;
    4- [2-hydroxy-3- (4-pheno-hydroxymethyl-piperidino) propoxy} -6-methoxycarbonylindole, m.p. 139-140 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -6-methyl-indole, m.p. 122-123 ° C;
    2-ethoxycarbonyl-4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] - 6-methyl-indole-benzoate, m.p. 189 ° C;
    4- [2-hydroxy-3- (4-2-chloro-phenoxymethyl-piperidino) -propoxy] -indole-benzoate, so pl. 140-142 ° C;
    4-3- ^ 2-hydroxy-3- [4- [3-chloro-phenoxymethyl) -piperidino-1-propoxy] -indole • benzoate, mp. 149-151 ° C;
    4 - {- 2-hydroxy-3- [4- (4-chloro-phenoxymethyl) -piperidino] propoxy! -indole "Beneoat, so pl. 156-158 ° C;
    4- {2-hydroxy-3- [4 (-2-methoxy-phenoxymethyl) -piperidin0] -propoxy] -indol-benzoate, m.p. 115-117 C;
    4- [2-hydroxy-3- [4- [3-methyl-phenoxymethyl) -piperidino] propoxy] indole-benzoate, m.p. 152-154 C;
    4- [2-hydroxy-3- [4- (2-methyl-phenoxymethyl) '- piperidino] propoxy] indole-benzoate, m.p. 128-129 ° C;
    4- (2-hydroxy-3- [4- (2-methylmercapto-phenoxymethyl (-piperidino) -propoxy]] -indole, mp 108-110 ° C;
    4- [2-hydroxy-3- [4- (4-fluoro-phenoxymethyl (-piperidino) -propoxy] 6-methyl-indole, mp, 137-139 ° C;
    4- [2-hydroxy-3- [4- (3-methyl-phenoxymethyl (-piperidino) -propoxy] -6-methyl-indole-benzoate, mp 138-140 ° C {
    4- [2-hydroxy-3- [4- (2-benzyloxy-phenoxymethyl (-piperidino) propoxyJ-indole (oil);
    .4- [2-hydroxy-3- (4-benzyloxy-phenoxymethyl-piperidino) -propoxy] -indole, m.p. 113 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -2-pivaloyloxymethyl-indole, m.p. 130-132 ° C;
    4- {2-hydroxy-3- [4- (2-methoxy-phenoxymethyl J-piperidino] propoxy] -2-methylindole, mp 137-138 ° C;
    4- [2-hydroxy-3- [4- (2-chloro-phenoxymethyl) piperidino] propoxy} -2-methylindole;
    4- [2-oxy-3 [-4- (2,5-dimethyl-phenoxymethyl) piperidino] propoxy] indole, m.p. 153-155 ° C;
    5- [2-hydroxy-3- (4-phenoxymethyl-niperidino) -propoxy] -indole, m.p. 121-
    123 ° C;
    6- [2-hydroxy-3- (4-phenoxymethic-piperidino) propoxy] indole, m.p. 144145 ° C;
    4- [3- (4-phenoxymethyl-piperidino) -propoxy] -indole, m.p. 118-119C;
    6- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -indole, m.p. 144145 ° C;
    4- [3- (4-phenoxymethyl-piperidino) propoxy] -indole, m.p. 118-119 ° C;
    5- [3- (4-phenoxymethyl-piperidino) propoxy] indole, m.p. 107-108 and C;
    6- [3- (4-phenoxymethyl-piperidino) propoxy] indole, mp. 123-124, C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -2-ethoxycarbonylindole, m.p. 168-170 ° C;
    . 4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] —2 — hydroxy-methyl-indole, so pl. benzoate 145-146 C;
    4- [2-hydroxy-3- (4-phenoxymethylpiperidino) propoxy] -6-hydroxymethyl-indolbenzoate, m.p. 153-155 ° C;
    4- [2-hydroxy-3- (4-phenoleimethyl-piperidino) propoxy] -6-hydroxymethyl-5-methyl-indole;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidines-propoxy] -indole-carboxylic acid, mp 218-220 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -2-indole-benzoate, $ mp. 145-148 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -6-methyl-indole, m.p. 122-) 23 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperi-GO dino) propoxy] -5,6-dimethyl-indole ;.
    4- [2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) propoxy] indole, m.p. 1ОЗ-1О5 ° С;
    4- [2-pivaloyloxy-3- [4- (2-methoxy-GO-phenoxymethyl) piperidino] propoxy J • indole, mp. 10 7 C;
    4- [2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) propoxy] -6-methylindole, m.p. 81 ° C; GO
    4- [2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) propoxy] -6-pivaloyloxymethyl-indole, m.p. 76-78 C;
    4- [2-benzoyloxy-3- (4-phenoxymethyl-piperidino) propoxy] indole, GO
    so pl. 108-110 ° C;
    4- [2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) propoxy] -2-pivaloyloxymethyl-indole, m.p. 93-95 ° C;
    4- £ 2-beer aloyloxy-3- [4- (2-methyl- 30 phenoxymethyl-) piperidino] propoxy] -2-methyl-indole;
    3S
    4— [2-hydroxy-3 - [- 4- (2-oxy-phenoxymethyl) piperidino] propoxy] indole, e.g. 119-121 ° C;
    4- [2-hydroxy-Z- £ 4- (4-hydroxy-phenoxymethyl) -piperidino] propoxy] indole, m.p. 167 ° C;
    4- £ 2-hydroxy-3- (4— (2-napa6oKCj — phenoxy — methyl ^ piperidino] propoxy] indole;
    4- {3- (4-phenoxymethyl-piperedino) propoxy] benzimidazole dihydrochloride, mp. 144-146 ° C;
    • 4- [2-hydroxy-3- (4-phenoxymethyl-piperi-45 dino) -propoxy] -benzimidazole-dihydrochloride, so pl. 123-125 ° C;
    4- [2-hydroxy-Z- £ 4- (, 2-methoxy-phenoxy-methyl) -piperidino] -propoxy ^ -benzimidazole-dihydrochloride, so pl. 144-145 th C; 50 azole dihydrochloride, mp 144-I45 C;
    4- [2-hydroxy-Z- £ 4- (3-methyl-phenoxymethyl) · piperidino] propoxy] benzimidazole dihydrochloride, mp. 118-120 ° C;
    4- [2-hydroxy-3- £ 4- (2-chloro-phenoxymethyl) piperidino] propoxy] benzimidazole dihydrochloride, mp. 140-142 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -6-methyl-benzimidazole dihydrochloride;
    4- [2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) propoxy] benzimidazole hydrochloride, m.p. 132-134 ° C;
    4- [2- (3,4-5-trimethoxybenzoyloxy) -3 [4- (2-chlorophenoxymethyl) piperidino] propoxy] benzimidazole, m.p. 157160 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] benzotriazole hydrochloride, mp. 187-189 b C;
    4- [2-hydroxy-3- (2-methoxy-phenoxymethyl) -piperidino) propoxy] benzotriazole hydrochloride, m.p. 161-162 ° C;
    4- (2-hydroxy-3- [4- (3-methyl-phenoxymethyl) piperidino] propoxy] benzotriazole hydrochloride, mp 206-208 ° C;
    4- £ 3- (phenoxymethyl-piperidino) -propoxy] -benzotriazole-hydrochloride, so pl. 259-260 ° C;
    4- [2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) propoxy] benzotriazole hydrochloride, mp. 131-133 ° C;
    4- £ 2- (4-methyl-benzoyloxy) 3- (4- (2-methoxy-phenoxymethyl) -piperidino] propoxy] benzotriazole;
    4- [2- (2-chloro-benzoyloxy) -3- (4-methyl-phenoxymethyl) piperidino-propoxy] benzotriazole;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] indazole, m.p. 142,143 ° C;
    4- (2-hydroxy-3- [4- (2-chloro-phenoxymethyl) piperidino] propoxy] indazole, mp 154 ° C;
    4- (2-hydroxy-3- (4) 2-methyl-phenoxymethyl (-piperidino) -propoxy] -indazole ^ mp 127-129 ° C .;
    4- £ 2-hydroxy-3- (4- (3-methyl-phenoxymethyl) piperidino] propoxy] indazole, mp 158-159 ° C .;
    4- {2-hydroxy-3- [4- (2-methoxy-phenoxymethyl) -piperidino] -propoxyJ-indazole, m.p. 151-153 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperi dino) -propoxy] -5-methyl-indaz ol, m.p. 156-157 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] -6-methyl-indazole, mp 152-153 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] indazole, m.p. 141142 ° C;
    3- acetoxymethyl-4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propoxy] indazole-hydrochloride, m.p. 203 “204 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) propo'xy] -3-hydroxymethyl-indazole9
    dihydrochloride, mp 183 ° C (decomposition);
    4- [2-hydroxy-3- (4-phenoxymethyl-pipeRidino) propoxy — J-7-methylindazole, mp. 132-135 ° C;
    4- [3- (4-phenoxymethyl-piperidino) -propoxy! -Indazole, mp 160-161 ° C;
    4- [2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy] -6-tert-butyl-indazole, m.p. 13O-131 ° C; __
    4- [2-pivaloyloisi-3- (4-phenoxy> methyl-piperidino) propoxy] indazole, mp 116 -8 ° C.
    权利要求:
    Claims (2)
    [1]
    a benzylxycarbonyl group or a lower alkyloxycarbonyl group. The invention also relates to a process for the preparation of salts of these compounds. The compounds of the formula I and their salts in pharmacologically active compounds: with slight toxicity, have pronounced vasodilating properties, - which manifest themselves in lowering blood pressure; in addition, they have the ability to suppress adrenergic receptors. The following is a description of how to get a variety of products like alcameras, a variety of products, and a variety of products. , R is hydrogen, halogen, and also N-ynz Q {N where R / 1 Re have the indicated value, is reduced with the help of complex metal hydrides or by catalytic hydrogenation, and cyclized. These are either in free form or in salt form. Salts, phosphoric, sulfuric, acetic, citric, maleic, and benzoic are the most suitable acids for obtaining the salts. The target products can be isolated as a racemate or optically active antipode Example 1. 2-Methyl-3-nitro "coxyphenol. 10.7 g (0.07 mol) of 2-methyl-3-nitrophenol are dissolved in 55 ml of epichlorohydrin, 7.9 g of NaOCH are added to the solution (o, 14 mol) in 75 ml of ethanol and stirred for 16 hours at room temperature. After removing the excess amount of epichlorohydrin in vacuo, the residue is taken up in ether and extracted three times with water. After drying the organic phase over O their salts, the compound of the formula OCiHzCHOHCJHgNHg has the indicated values, they are reacted with the compound of the formula Z-R, where R has the indicated value, and Z means the reactive esterified into the complex hydroxyl group fl. The purpose of the invention is the expansion of the range of products acting on the willow organism. The goal is achieved by a method that is based on the known reaction of forming a hetero ring when the cycle is closed by 2 carbon atoms of the side chain of 0-amino - (or nitro) phenyl compounds when heated in the presence of a reducing agent: G2. In accordance with the invention, a process for the preparation of aminopropanol derivatives of the indicated formula I is described, which consists in that the compounds of the formula H-eHg-N -dHgO HartSO and evaporation leave 17 g of oil, which, after grinding with isopropanol and ligroin crystallisation, is there, after suction crystals receive 8.6 g of 2-methyl-3-nitro-epoxyphenol with so pl. 46-48 C (58% of theory). Example 2. 1- (2-hydroxy-3} -4-phenoxymethyl- (piperidino) -propoxy-; 2-methyl-3-nitrophenol. 4.2 g (0.02 mol of the title compound are dissolved in 100 ml of n- butanol and mixed with 3.8 g (0.02 mol) of 4-fechoxymethyl-1 peridine .. After standing for overnight at room temperature, the resulting crystals are sucked off, washed with a small amount of ligroin and 6.9 g of the title compound are obtained. -} 104 ° C (, 86% of theory. Example 3. 1- (2-hydroxy-3) -4-phenoxymethyl- (piperidino) -propoxy - 2-dimethyl-amino-ethylene-3-nitrobenzene. 589, 3 , 0 g (0.0075 mol) of this compound is dissolved in 20 ml imethylformamide, mixed with 1.6 ml (0.011 mol) N, M-dimethylformamide dimethyl acetal and heated for 8 hours during the distillation of the resulting alcohol to reflux. After evaporation in vacuum, 4.0 g of an oily residue remain. Example 4. 4- (2- hydroxy-3H4-phenoxymethyl-piperidino (-propoxy) -indole 4.0 g of the indicated crude product is suspended in 150 ml of methanol, mixed with 1.0 g of 10% palladium on carbon and shaken with hydrogen for 2 hours. After the hydrogen uptake is complete, the catalyst is filtered off, the solution is evaporated, dissolved in ethyl acetate, and benzoate is obtained by adding the calculated amount of benzoic acid. Output 1.5 g (39% of theory), so pl. 145-147s. Similarly, receive; 4- 2-hydroxy-3-C4-phenoxymethyl-piperidino) -propoxy-indole, m.p. 127129 С (in the form of acetate); 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy -2-ethoxycarbon-1-indole, m.p. 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-2-carbamoyl-indole, m.p. 182 С; 4-C2-OXI-3- (4-phenoxymethyl-piperidino-propoxy-2-dimethylaminocarbonyl-indole, mp. 178 C; 4-2-hydroxy-3- (4-phen6xymethyl-piperidino) -propoxy 1-6- methoxycarbonylindole, mp 139-140 ° C; 4-12 hydroxy-3-14-phenoxymethyl-pyridine-propoxy-6-methyl-indole, mp 122-123 ° C; 2-ethoxycarbonyl-4-C2- hydroxy-3- (4-phenoxymethyl-piperidino) .- propoxy-6-methyl-indole-benzoate, mp 189 C; 4 -2-hydroxy-3 - (, 4-2-chloro-phenoxymethyl-piperidine) α-propoxy-indole-benzoate, mp 140-142 ° C; 4-3- (2-hydroxy-3-4-13-chloro-fecock simethyl) -piperidino propoxy-indole benzoate, m.p. lA9-15lCj 4 - {- 2-hydroxy-3 - 4-C4-chloro-phenoxymethylUpiperidino-propoxy | -indole-benzoate, m.p. 156-158 C; 4-G2-OXI-3-C4 (-2-methoxy-phen-6-methyl) -piperidine-propoxy-1-indol-benzoate, m.p. 115-117 ° C; 4-f2-OKCH-3-C4- (3-methyl-phenoxymethyl) -piperidino-propoxy-indol benzoate, m.p. 152-154 ° C; 09754 4- {2-hydroxy-3-G4- {2-methyl-phenoxymethyl) -piperidano3 propoxy} -indole-benzoate, m.p. 128-129C; 4- {2-hydroxy-3- 4- (2-metsh1mercapto} -phenoxymethyl (-piperidino; -propoxyT-indole, mp. 108-1 ° C; 4-C2-hydroxy-3-C4- (4-fluoro -phenoxymethyl (-piperidino) -propoxy 6-methyl-indole, t.pcs 37-139 С; 1v 4- {2-hydroxy-3-C4- (3-methyl-phenoxymethyl (-piperidino) -propoxy-6- methyl-indole-benzoate, mp. 138-140 ° C; 4- {2-hydroxy-3-C4- (2-benzsh10xy-phenoxymeth1 (-piperidino) -propoxy1-indole | $ (oil);, 4- C2-hydroxy-3- (4-benzyloxy-phenoxymethyl-piperidino} -propoxy-indole, so that 4-C2-hydroxy-3- (4-phenoxymethyl-pipe-mridino) -propoxy -2-pivaloyloxymethyl- indole, mp 130-132 C; 4-C2-hydroxy-3-C4- (2-methoxy-phenoxymethyl | -piperidino3-propoxy -2-metsh1indol, mp 37-138s; And 4-C2-hydroxy-3-C4- (2-chloro-phenoxymethyl) -piperidino-propoxy} -2-metsh1indole; 4- (2-oxy-3 - 4- (2,5-dinetyl-phenoxymethyl) -piperidino-propoxy} -indole, EOpl. 153-155 ° C; 5-2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-indole, t mp 121123 ° C; 6- 2-hydroxy-3- (4-phenoxymethyl-pipajjridino) -propoxy-indole, mp 144145 s; 4-HZ- (4-phenoxymethyl-piperidino) -propoxy-indole, t .pl. P8-119s; 6- 2-hydroxy-3- (4-phenoxymethyl-piper40ridino) propoxy-1-indole, m.p. 144.145 ° C; 4-GZ- (4-fe: Noxymethyl-piperidino) -propoxy-indole, m.p. 118-119C; . (4-phenoxymethyl-piperidino) 4 $ -propoxy-indole, m.p. 107-108 ° C; 6- 3- (4-phenoxymethyl-piperidino) -propoxy-indole, m.p. 123-124, C; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy -2-ethoxycarbonyl indole, m.p. 168-170 ° C; . 4-G2-hydroxy-3- (4-phenoxymethyl-pipet.ridino) -propoxy} -2-oxy-methyl-indole, m.p. benzoate 145-146 C; 4- 2-hydroxy-3- (4-phenoxymethylpipe. -Ridino) -propoxy-6-hydroxymethyl-indol-benzoate, m.p. 153-155C; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-b-hydroxymethyl-3-me-, til-indole; 78 4- 2.-hydroxy-3- (4-phenoxymethyl-PIPeridino-propoxy-indole-carboxylic acid, mp 218-220 ° C; 4-2-hydroxy-3- (4-phenoxymethyl-piperidino) - propoxy -2-indole-benzoate, mp. 145-148 ° C .; 4- .2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-6-methyl-indole, mp. 122-123 ° C; 4- 2-hydroxy-3- (.4-phenoxymethyl-piperi-dino-j-propoxy-5,6-dimethyl-indole; 4-2-pivapoyloxy-3- (4-phenoxy-methyl-piperidino) -propells -indole, mp 103-105 ° C; 4- {2-pivaloyloxy-3-4- (2-methoxy-phenoxymethyl1-piperidino-propoxy} indole, mp 10 7 C; 4- 2-pivaloyloxy -3- (4-phenoxyme-1-piperidino) -propoxy-6-methylindole, T.pl. 81 C; 4-2-pivo Lexi-3- (4-phenoxymethyl-piperidino) -propoxy-6-pivaloyloxymethyl-indole, mp 76-78 C; 4-2-benzoyloxy-3- (4-phenoxymethyl-piperidino) -propoxy-indole, t 108-PO ° C; 4- 2-pavaloyloxy-3- (4-phenoxymethyl-piperidino) -propoxy -2-piBaloyl oxymethyl-indole, mp 93-95.C; 4- {2-pivaloyloxy -Z-4 - (, 2-methylphenoxymethyl-) -piperidino-propoxy -2-methyl-indole; 4- 2-hydroxy-3-4- (2-oxy-phenoxymethyl), - piperidino3-propoxy-indole, T .nh. 119-121 ° C; 4- | 2-hydroxy-3-C4-4-hydroxy-phenoxymethyl) .- piperidino-propoxy | -indole, m.p. 167 ° C; 4- 2-hydroxy-3- C4- (2-parabox1-phenok methyl} -piperidino-propoxy-J indole; 4- {3- (4-phenoxymethyl-piperidino) -propoxy-benzimidazole dihydrochloride so pl. 144- 46 ° C; XJJ. "-T-T4-TV, 4-2-OXI-3- (4-phenoxymethyl-piper wildly) -propoxy-benzimidazole-dihydrochloride, mp 123-125 C; 4-G2- OXI-3-C4- (.2-methoxy-phenoxy-methyl) -piperidino-propoxy-benzim azole-dihydrochloride, mp 144j-45 Cj 4- {2-hydroxy-3-4- (3-methyl- phenoxyme-piperidino-propoxy-benzimidazole dihydrochloride, mp 118-120 ° C; 4- {2-hydroxy-3-4- (2-chloro-phenoxymethyl) -piperidino-propoxy} benzimidazole-dihydrochloride, mp 140-142 ° C; 4- 2-hydroxy-3- (A-pheno xymethyl-piperndino) -propoxy-6-methyl-benzimidaz dihydrochloride; 4-2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) -propoxy-benzimidzol hydrochloride, i.e. 132-134s; 4-G2- (3 , 4-5-trimethoxy-benzoyloxy) (2-chlorophenoxymethyl) -piperidio-propoxy-benzimidazole, mp 1574-2-hydroxy-3- (4-phenoxymethyl-piperidino) proproxy, benzotriazolhydrot. Mp 187 -189 C; loride, 4- 2-hydroxy-3- (2-methoxy-phenoxyethyl-piperidino) -propoxy-benzoria-ol hydrochloride, so pl. 161-162 ° C; 4- {2-hydroxy-3- 4- (3-methyl-phenoxyethyl) -piperidino-propoxy-benzoriazole hydrochloride, m.p. 206-208 С; 4- 3- {phenoxymethyl-piperidino) -propoxy-benzotriazole hydrochloride, m.p. 259-260 ° C; 4- 2-pivaloyloxy-3- (4-phenoxymethyl-piperidino) -proyl 1-benzotriazole hydrochloride, so pl. 131-133 ° C; 4- {2- (4-methyl-benzoyloxy) 3- 4-2-methoxy-phenoxymethyl) -piperidino-propoxy} -benzotriazole; 4- 2- {2-chloro-benzoyloxy) -3- (4-methyl-phenoxymethyl) -piperidino-propoxy-benzotriazole; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-indazole, m.p. 142143 ° C; 4- {2-hydroxy-3- 4- (2-chloro-phenoxymethyl) -piperidino-propoxy} -indazole, m.p. 154 ° C; 4- 2-hydroxy-3- (4) 2-methyl-phenoxymethyl (-piperidino) -propoxy-indazole m.p. 127-129 ° C; . 4-C2-OXI-3- 4- (3-methyl-phenoxymethyl) -piperidino-propoxy} -indazole, m.p. 158-159С; 4- -oxo-3- 4- (2-methoxy-phenoxymethyl) -piperidino-D-propoxyJ-indazole, l 151-153 С; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-5-methyl-1chazol, m.p. 156-157 0; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-6-methyl-indazole, m.p. .152-153 ° C; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-indazole, m.p. 141142 ° С; 3-acetoxymethyl-4-2-hydroxy-3- (4-phenxymethyl-piperidino) -propoxy-indazole hydrochloride, mp. 203 204 ° C; 4- 2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-3-hydroxymethyl-indazol-dihydrochloride, m.p. 183 ° C (decomposition of 4-G2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-J-7-methylindazole, mp 132-135 0; 4-GZ- (4-phenoxymethyl-piperidino) - propoxyZ-indazole, mp 160-161 C; o 89097510 -4-G2-hydroxy-3- (4-phenoxymethyl-tteridino) -propoxy 1-6-tert-butyl indaeol, mp nO-ni C ; 4-f 2-pivalo1ssn-3- (4-phenoxy-methyl-piperidino-propoxy-indazole, T..PL. 116-118 ° C. The invention The method for producing aminopropanol derivatives of the general formula 1
    - iT VftlaO
    where R and RQ may be the same or different and denote a hydrogen, lower alkyl group, oxyalkyl group, (low alkanopp), pxa alkyl group or —CO — Z group, and Z means hydroxyl group, lower alkyloxy group or. Rt group N, in which Rt and RY MAY be the same or different means hydrogen, lower alkyl group or oxyalkyl group; RJ means hydrogen or a group -0-Rg, and Rn means hydrogen, a lower alkanoyl group or an aroyl group which may be for CHs. - i: ic} H C. dHj where R-Rj have the indicated meaning, is reduced using complex hydrides metals or by catalytic. hydrogenation and acidification followed by allocation of the desired products in free form or in the form of salts. acknowledged priority
    Meshchena by halogen, lower alknlszh, lower alkyloxy, apkoxycarboshshom, hydroxal group, the alklktg ogruppoy, nitripnoy group, nitro-group or trifluorimetry group;
    R and may be the same or different and mean hydrogen, ha. Ftj is a log, hydroxyl group, benzyloxy group, lower alkyl group, lower alkyloxy group, lower alkylthio group, carboxyl group, benzyloxycarbonyl group or lower alkyloxycarbonyl group, or their salts, That connection is forschy with mules. -eHg-VcJKzC-f; , 12.11.76R (eG hydrogen 20.08.77R3 - group -O-R Sources of information taken into account during the examination 1.Patent of Switzerland No. 516515, class C 07 C 93/14, published 1972.
    [2]
    2. Heterocyclic compounds. Ed. R. Elderfield, t.Z., M.E. 1 {foreign literature 1954, p. 27
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19762651574|DE2651574A1|1976-11-12|1976-11-12|3-Phenoxymethyl-piperidino 1-heterocyclyl-oxo-propane derivs. - useful as vasodilators and beta adrenergic receptor inhibitors|
    DE19772737630|DE2737630C2|1977-08-20|1977-08-20|
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