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    公开号:SU810079A3
    申请号:SU792745301
    申请日:1979-04-06
    公开日:1981-02-28
    发明作者:Видеманн Фритц；Кампе Вольфганг；Тиль Макс；Шпонер Гисберт；Роеш Эгон；Дитманн Карл
    申请人:Берингер Маннхайм Гмбх (Фирма)；
    IPC主号:
    专利说明:

    (54) A METHOD FOR OBTAINING CARBAZOLYL- (4) -OXIPROPANOLAMINE DERIVATIVES OR THEIR SALTS (ITS OPTIONS) to keep 1-6, preferably 1-4 carbon atoms. The methoxy and ethoxy methylmercapto methylsulfinyl and methylsulfonyl groups are preferred. Aralkoxy means predominantly benzyloxy. The symbol A g means a carboxylic mono- and bicyclic aryl jOCTaToic., And the ring can also be partially hydrogenated. Preferred are phenyl, naphthyl, indanyl tetrahydronaphthyl residue. As an example of a residue in which R 4 and R together form the -CHD-O-group, if X is an oxygen atom, a 1,4-benzodioxanyl- (2) -methyl residue should be mentioned. The compounds of formula (I); and their physiologically tolerable salts show, in a pharmacological test, a vasodilator and P) receptor-blocking effect, so that these compounds are suitable for treating and preventing circulatory diseases and heart diseases, for example elevated blood pressure, angina pectoris (spasm of the coronary vessels of the heart). The method consists in carrying out the reaction of exchange of the compound of the formula O-CHj-Cft-CHi-Y,. where Y is halogen or sulphonate, R has the value indicated for R (or Y and together, simply reacts with a compound of the formula R (y HN — CH — CH X — Ar (11 Rj. 4 61 X, Ar, R5 and R having the indicated values or exchanging a compound of the formula O-CHg-CH-CHg-HH I O, RZ where R and R 2. have the indicated meanings with a compound of the formula, J-Y-CH-CH-X-Un Rj R where y, R, R, X, A g RC and R, have the above values and the target product is isolated in free form or as a salt. These methods are expediently carried out in an organic solvent which is inert under the reaction conditions, For example, toluene, dioxane, ethylene glycol dimethyl ether, isopropanol or dimethylformamide, under certain conditions, in the presence of an acid binder. Reactions of the epoxide of formula (II) (Y and R together mean a valence line) with the amine of formula (ill) can it is also possible to mix the components of the reaction when standing, at room temperature, or when heated. Lmercapto groups in alkylsulfinyl or alkylsulfonyl group. Further, it is possible to subject the hydroxy groups to the formation of groups of simple or complex ethers or, conversely, to translate the group of simple or I complex esters into hydroxy groups. To convert the compounds of formula (1) into their salts, these compounds are exchanged, predominantly in an organic solution medium, with an equivalent amount of inorganic acid, for example, hydrochloric, hydrobromic, phosphoric, sulfuric, acetic, citric and maleic acids. The compounds of formula (1), which represent racemic mixtures, can be separated through their corresponding diatheomeric salts into optically active forms. For the resolution of the racemate, for example, tartaric, block acid, camphor acid and camphorsulfonic acid can be used. Example 1. 1-carbazolyl- (. 4) -oxy-3- 2- (2-methoxy-phenyl) -ethylamino -prrpanol- (2). 6 g of 4- (2,3-epoxypropoxy) -carbazole and 7.6 g of 2- (2-methoxyphenyl) -ethylamine are stirred for 20 hours at 70 ° C. Triturated with diethyl ether, etched off and crystallized from ethyl acetate using activated charcoal and bleaching clay. Yield 6 g (61% of theory). Colorless crystals, T ... PL. 135-136 ° C. In a similar way, a) 1-carbosolyl- (4) -oxo-J-3- 2- (3, 4-dimethoxyphenyl) -trimyl-1–3H-propanol- (2) is obtained. Output 42% of theory, T. pl. 129-130 C, and acetic acid salt, so pl. 180-183 ° C, from 4- (2,3-epoxypropyl) -carbazole and 2- (3,4-dimethoxyphenyl) -ethylamine. b) 1-carbazolyl- (4) -oxy-3- 2- (2-pyridyl) ethylamino-propanol- (2). Output 32% of theory, so pl. 105-107s, from 4- (2,3-epoxypropoxy) -carbazole 1 2- (2-pyridyl) -ethylamine. c) 1-carbazolyl- (4) -oxyJ-3- 2- (4-pyridyl) -ethylamino-propanol- (2). Output 24% of theory, so pl. 8b-88 ° C, from 4- (2,3-epoxypropoxy) -carbazole and 2- (4-pyridyl) .- ethylamine. d) 1-; kp1rbazoltsl- (4) -oxy-3- (3-phenylpropylamino) -propanol- (2) ,. Yield 30% of theory and sol nta: rna acid, so pl. 98-99 ° C, from 4- {2,3-epoxypropoxy) -carbaeol and 3-pheny propylamine. e) 1-carbazolyl- (4) -O1ssi-3-4-phenylbutyl- (2) -amino-propa ... NOL- (2). Output 13% of theory, so pl. 124-125 ° C, from 4- (2,3-epoxypropoxy-carbazole and 4-phenylbutyl- (2) -al5In Example 2. 1- Carbazolyl- (4-oxo -2 -2- (2-met6-xyphenoxy) -ethyl amino propanol- (2). 22.6 g of 4- (2,3-epoxypropoxy) -bazol and 17.4 g of 2- (2-methoxyphenoxy-ethylamine in 75 ml of dimethyl ether. ethylene glycol are mixed at 25 50 ° C. The mixture is introduced into the evaporator with a rotational effect, evaporated to dryness, triturated with diethyl ether with ether and recrystallized from ethyl acetate and using activated carbon. 15.1 g yield (39% of theory). Colorless crystals, t mp 114-115 ° C. Braz receive: a) 1-carbazolyl- (4) -oxy-3- (2-phenoxyethylamino) -prop ol- (2). Yield 32% of theory, mp 105-107 C out of 4 - (- 9 -epoxypropoxy) -carbazole and 2-phenoxyethylamine, b) 1-carbazolyl- (4) -oxy - 3- 1-phenoxypropyl- (2) -amino-propane; NOL- (2). 31% yield from theory and hydrochloric - salt, mp.11b-119 C from 4- (2,3-epoxypropoxy) -carbazole and 1-phenoxypropyl- (2) -amine. c) 1-carbazolyl- (4) -oxy., 4-benzodioxanyl -2) -methylamino-prop nol- (2). Output 28% of theory, so pl. 129-131 ° C, from 4- (2,3-epoxyprop-6xy) -carbazole and 2- (aminomethyl) -1,4-benzodioxane .. d) 1-carbazolyl- (4) -oxy-3- 2- (4 -carbamoylphenoxy) -ethylamino-propanol- (2). Output 13% of theory, so pl. 120-122 C, from 4- (2,3-epoxypro-coxy) -carbazole and 2- (4-carbazoylphenoxy) -ethylamine. Example 3. 1-carbazolyl- (4) -oxy 1-2- 2- (2 -ethoxyphenoxy) -ethyl-: amino -pr6panol- (2). . b g of 4- (2,3-epoxypropoxy) -carbazole and 9.1 g of 2- (2-ethoxyphenoxy) ethylamine are stirred for 20 hours at 70 ° C. After cooling, it is stirred with diethyl ether, the residue of ethyl acetate is recrystallized, and the residue is recrystallized using activated carbon and clay. Yield 4.4 g (42% of theory). Colorless crystals, melting point 127.5-128 ,. In a similar way, a) 1-carOazolyl- (4) -oxy-3-2- (4-florphenoxy) ethylamino-propanol- (2) is obtained. Output. 56% of theory, so pl. 145-146 s, from 4- (2-, 3-epoxypropoxy) -carbazole and 2- (4-fluorophenbxy) -ethylamine. b) 1-carbazolyl- (4) -oxy-3-2- (4-tert.butylphenoxy) -ethylamino-propanol- (2). The output of 51% of theory, so pl. 127-128 ° C from 4- (2,3-epoxypropoxy) -carbazole and 2- (4-tert.butylphenoxy) -ethylamine. c) 1-carbazolyl- (4) -oxy-3- 2- (2, 3-dimethylphenoxy) -ethylamino} -prrpanol- (2). Yield 51% of theory, mp, 128-129c, from 4- (2,3-epoxypropoxy) -carbazole and 2- (2,3-dimethylphenoxy) -ethylamine. . d) 1-carbazolyl- (4) -oxy7 -3- | 2- indinali- (5) -oxy ethylamino} -propanol- (2). Output 54% of theory, so pl. 143-145 ° C, from 4- (2,3-epoxypropoxy) -carbazole and 2-indanyl- (5) -oxyethylamine. e) 1-carbazolid- (4) -oxide-3-J2-naphthyl- (1) -oxy-ethylamino | propanol- (2), Output 64% of theory, so pl. 116-119c, from 4- (2,3-epoxypropoxy) -carbaeol and 2-naphthyl- (1) -oxy-ethylamine. e) 1-carbazolyl- (4) -oxy-3- 2- (3, 4-methylenedioxyphenoxy) -ethylamino-propanol- (2). Yield 32% off. theories, so pl. 142-143 ° C, from 4- (2,3-epoxypropoxy) -carbazole and 2- (3,4-methylenedioxyphenoxy) -ethylamine. g) 1-carbazolyl- (4) -okri-3- 2- (2,6-dimethoxyphenoxy) tethylamino-propanol- (2). Yield 65% of theory, rii, so pl. 136-138 ° C, from 4- (2,3-epoxypropoxy) -carbazole and 2- (2,6-dimethoxyphenoxy) -ethylamine. h) 1-carbazolyl- (4) -oxy-3- 2- (2-methoxyphenoxy) -propylamino-propanol- (2). Output 83% of theory, so pl. 137-157 ° C cheese, according to the degree of purity, a mixture of diastereomers, hence, a two-fold recrystallization of 22% of theory, ethyl acetate, m.p. 173-175c, from 4- (2,3-epoxypropoxy) -carbazole and 2- (2-methoxyphenoxy) -propylamine. and) 1-carbazolyl- (4) -oxide-3- (2-methylmercaptophenoxy) -ethylamino-propanol- (2). Output 40% of the theory, so pl. 83-85 ° C, from 4- (2,3-epoxyropoxy) -carbazole and 2- (2-methylmeraptophenoxy) ethyl amine. . k) 1-carbazolyl- (4) -oxy (2-benzyloxyphenoxy) -ethylamine propanol- (2). Output 36% of theory. 138-139 ° C, from 4- (2,3-epoxyropoxy) -carbazole and 2- (2-benzylenoxy) -ethylamine. In the examples, Sv, g, e, g, and the attached source amines can be prepared by exchange reactions using the corresponding nitrile. 2,3-Dimethylphenoxy-acetone tril. 100 g of 2,3-dimethylphenol, 57 ml of chloroacetonitrile, 110 g of potassium carbonate and 2 g of potassium iodide in 300 ml of methyl ethyl ketone are stirred for 5 hours under the action of a reflux condenser. The mixture is filtered off with suction, evaporated and the residue distilled and 88 g of colorless oil are obtained, b.p. 137-142 ° C at 13 mm. Similarly produced by the exchange reaction of 5-indanol; 3,4-methy lendioxyphenol and 2- (methylmercapto) -phenol, respectively, with chloroacetonitrile: indanyl- (5) -oxy-acetonitrile, b.p. 162-165 ° C at 14 mm; 3,4-methylenedioxyphenoxyacetonitrile bp. 1-70-175 C at 12 mm; 2-methyl mercapto-phenoxy-acetonitrile, m.p. 5b-58C, t. Kip. 173-17bc at 12 m 2 - (. Indanyl- (5) -oxy) -ethylamine. 109 g of indanyl- (5) -oxiacetonitrile in the presence of a skeletal nickel catalyst according to Renee in 700 ml of ethanol and 180 ml of liquid ammonia are hydrogenated at 110 atm. After distillation, 86 g of a colorless oil are obtained, b.p. 154-156 ° C at 12 mm. In a similar way, it is obtained from 2,3 dimethylphenoxyacetonitrile or 3,4-methylenedioxyphenoxyacetonitrile by hydrogenation: 2- (2,3-dimethylphenoxy) -ethylamine, b.p. 129132 С at 12 mm; 2- (3,4-Methyl-Dioxy Phenoxy) -ethylamine, b.p. 1b2-164 ° C at 13.mm. 2- {2-Methylmercaptophenoxy) -ethylamine. 26.7 g (2-methylmercaptophenoxy) -acetonitrile restore 8.5 g of lithium aluminum hydride in 1.3 g of diethyl ether (boil for 4 hours under the action of a reflux condenser). After conventional treatment and distillation, 21 g of a colorless oil are obtained, b.p. 117-120 ° C at 0.1 mm. In a similar way, it is obtained by reduction of 2, b-dimethoxyphenoxyacetonitrile: 2- (2,6-dimethoxyphenoxy) -ethyls bp. 160-162 with at 12 mm. Example 4. Carbazolyl- {4) -oxy -2- 2- (2-methylphenoxy) -thylamino-propanol- (2). b g of 4- (2,3-epoxypropoxy) -carbazol and 7.6 g of 2- (2-methylphenoxy) ethylamine are stirred at 70 s for 20 h. The mixture is dissolved in methylene chloride and separated by chromatography on a column of silica gel (500 ml) with the use of solvents: methylene chloride, a mixture of methylene chloride and ethyl acetate (9: 1 and 7: 3), ethyl ether and hydrochloric acid, and a mixture of ethyl ether ethyl acetate with methanol (9: 1). The sequence of the following steps during the laundering of the adsorbent: tertiary amine, acinic amine, primary starting material after trituration with diethyl ether recrystallization from ethyl phyracetic acid using a captive carbon and bleaching line get 5,2 g (53% of theory) color crystals m.p. 1252bs In a similar way, a) 1-carbazol-4 (4) -oxy (3-methylphenoxy) ethylamino-pro-NOL- (2) is prepared. The output of 43% of theory. 123-130C, from 4- (2,3-epoxyropoxy) -carbazole and 2- (3-methylenoxy) -ethylamine. b) 1-carbazolyl- (4) | -oxy-32- (2-chlorophenoxy) -ethylamino-propanol- (2). Output 26% of theory, so pl. 11-112 ° C, from 4- (2,3-epoxypropoxy) arbazole and 2- (2-chlorophenoxy) ethylmine. c) 1-carbazolyl- (4) -oxy-3- 2- (3-methoxyphenoxy) ethylamino-propanol- (2). Output 22% of theory so pl. , from 4- (2,3-zipoxipropoxy) -carbazole and 2- (3-methoxyphenoxy) -ethylamine. d) 1-carbazolyl (4) -oxy-3- 2- (4-methoxyphenoxy) -ethylamino-propanol- (2). The output of 48% of theory, so pl. 10b-108 ° C, from 4- (2,3-epoxypropoxy) -carbazole and 2- (4-methoxyphenoxy) -ethylamine. e) 1-carbazolyl- (4) -oxy-3- 2- (2-methoxyphenylmercapto) -ethylamino 3-propanol- (2). Yield 15% of theory, mp, 108-109 C, from 4- (2,3-epoxy-propoxy) -carbazole and 2- (2-methoxyphenylmercapto) -ethylamine. e) 1-carbazolyl-4-oxy-3-1- (2-methoxyphenoxy) propyl- (2) -amino-propanol- (2). Exit 85% of theory, so pl. 112-125 ° С (cheese according to the degree of purity; mixture of diastereomers); colorless crystals are obtained from this mixture by recrystallization from ethanol, ethyl acetate and toluene / isopropanol mixture, m.p. 140-141 ° C, and from the stock solutions - an additional amount of the product, so pl. 121.5-122.5 ° C, from 4- (2,3-epoxypropoxy) -carbazole and 1- (2-methoxyphenoxy) propyl- (2) -amine. g) 1-carbazolyl- (4) -oxy -2- 2- (2-methylsulfinylphenoxy) -ethylamino-propanol- (2). 25% yield of theory, oxalate from 12bc decomposition, from 4 - (. 2,3-epoxypropoxy-carbazole and 2- (2-methylsulfinylphenoxyethylamine). The compound is obtained by oxidation of 1-carbazolyl- (4) -oxy-3- 2- ( 2-methylmercaptophenoxy) -ethylamino-propanol- (2) by means of an equivalent amount of hydrogen peroxide in acetic acid at room temperature. The starting amines of examples 4d, c and g can be obtained by exchange reactions as follows (2- {2-methoxyphenylmercapto) hetilamine. By the exchange reaction with (2-chloroethyl mercapto) -anisole in liquid ammonia (8 h 120 C): oil, bp. 118-122 ° at 0.05 mm, hydrochloride salt - 1bЗ-167 ° С. 1- (2-Methoxyphenoxy) -propyl- (2) -amine. Hydrogenation of 2-methoxyphenoxyacetone in an ammonia / ethanol mixture (120 atm, 90 C); oil, so kip. 144146 C at 13 mm, oxalate, t, pl. 199 200 C (decomposition). 2- (2-Methylsulfinylphenoxy) -ethyl amine. By the oxidation of 2- (2-methy: tI meccaptp) -ethyl-amine-l equivalent to rehydro (30%) in acetic acid at room temperature; oil, oxalate, so pl. 174-175 ° C. h) 1-carbazolyl- (4) -oxy-3 - f 3- (2-methoxyphenyl) -propylamino-propanol- (2). The output of 45% of theory, so pl. 102-104 C of 4- (2,3-epoxyprop-6-methoxy) -carbazole and 3-t2-methoxy-phenyl) -propylamine. Example 5. 1- Carbazolyl- (4) -oxy-3-N-benyl-2- (2-methoxy-phenoxy) -ethylamino-propanol- (2-). 15.1 g of 4- (2,3-epoxy) -carbazole and 16.2 g (2-metoxy phenoxy) ethyl 1-benzylamine in 50 ml of ethylene glycol dimethyl ether are heated for 24 hours under the action of a reflux condenser. Bring to dryness, purify over silica gel with solvents: methylene chloride, a mixture of methylene chloride with ethyl acetate (9: 1 and 7: 3), ethyl acetate, and triturate the residue of the main fraction with diethyl ether. Output i5 g (80% of theory). Colorless crystals, pl. 97-99 S. In a similar way, a) 1-carbazolyl- (4) -oxy-3-, m-methyl-2- (2-methoxyphenoxy) ethyl ethyl-propanol- (2) is obtained. Yield 22% of theory; Colorless oil, hydrochloric mixture, m.p. 109C (slight gas formation), from 4- (2,3-epoxypropoxy) -carbazole and N-methyl-2- (2-methoxyphenoxy) -ethylamine. b) 1-carbazolyl- (4) -oxy1-3-N-butyl-2- (2-methoxyphenoxy) ethyl ethyl propanol (2). 84% yield of the yield. Colorless oil, hydrochloride salt, m.p. 169-170 ° C, of 4- (2,3-epoxypropoxy) -carbazole and N- 2- (2-methoxyphenoxy) ethyl butyl amine. c) 1-carbazolyl- (4) -oxy-3-n-6-benzyl-2- (5-carbamoyl-2-pyridyl-oxy) -ethylamino-propanol- (2). Output 80% of theory, so pl. 175-167 ° C, from 4- (2,3-epoxypropoxy) -carbazole and (5-carbamoyl-2-pyridyloxy) -ethyl y-benzylamine. Example 6. 1-carbazolyl- (4) -oxy -2-formyloxy-3-m-benzyl-2- (2-methoxyphenoxy) ethylamino-propane hydrochloride. On 7.9 g of 1-carbazolyl- (4) -oxy-3-N-benzyl-2- (2-methoxyphenene) -ethylamino-propanol- (2) is treated with a mixture of formic anhydride and acetic acid, prepared from 3 ml of formic acid acid and 6 ml of acetic anhydride, 2.5 days at room temperature, poured into ice water, neutralized with sodium bicarbonate solution, extracted with methylene chloride and from the residue solution after extraction in diethyl ether, precipitated hydrochloride salt. Output 8.1 g (91% of theory). Colorless crystals, starting from 85 ° C, are sintered from 120s. Bubbles are formed. . PRI me R 7. 1- Kapabazolyl-. (4) -ox-3-pivaloyloxy-3-m-benzyl-2- (2-methoxyphenoxy) ethylamino-propane hydrochloride. To a solution of 7 g of 1-carbazolyl (4) -oxy-3-fN-benzyl-2- (2-methoxyphenoxy) ethylamino 1-propanol (2) in 35 mm of pyridine was added 1.9 ml of pivalic acid chloride. After settling overnight, it is poured into water, absorbed by methylene chloride ,. is purified by chromatography over silica gel, and the hydrochloride salt is precipitated from a solution of the base in diethyl ether. The output of 6.6 g (77% of theory). Colorless crystals, starting from sintering, so pl. 120 ° C (slight gas formation). Similarly, by using benzoylation, 1-carbazolyl- (4) toxy-2-benzoyloxy-3-n-benzyl-2- (2-methoxyphenoxy) ethylamino-propane hydrochloride is obtained. Output 70% of theory, so pl. 113 ° С (weak gas formation). Example 8. 1- Carbazolyl (4) -oxy-3-formyloxy-3- 2- (2-methoxyphenoxy) ethylamino t-propane hydrochloride. 2.2 g of 1-carbazolyl- (4) -oxy -2-formyloxy-3-C-benzyl-2- 12-metroxyphenoxy) ethylamino-propane hydrochloride is hydrogenated in 40 ml of abs. Tetrahydrofuran in the presence of 0.3 g of 10% - Palladium on coal at normal pressure. After suction and evaporation, a precipitate is obtained which, on treatment with diethyl ether, becomes crystalline. Output 1.3 g (70% of theory). Colorless Ristaly, so pl. 62 ° С (with formation of bubbles). In a similar way receive:
    a) 1-carbazolyl- (4) -oxy-2-pivoyl-3-2- (2-methoxyphenoxy) ethylamino-propane-hydrochloride, Vyod 85% of theory, so pl. 199-201С (insignificant gas formation), by hydrogenolysis of 1- carbazolyl-
    - (4) -oxy -2-pivaloyloxy-3-N-benzyl-2- (2-methoxyphenoxy) ethylamino-propane hydrochloride.
    b) 1-carbazolyl- (4) -oxy-2-benzoyloxy-3- 2- (2-methoxyphenoxy) -e tylamino-propane hydrochloride. Output 84% of theory, so pl. 102 ° C (during gas formation), by means of hydrogenolysis of 1-: carbazolyl- (4) -oxy Z-2-benzoyloxy-3-1M-benzyl-2t (2-methoxypheno-; si) ethylamino-propane hydrochloride. 15
    c) 1-carbazolyl- (4) -oxy-3-2- (5-carbanoyl-2-pyridyloxy) 1-ethylaminopropanol- (2). M.p. 176178 ° C, by means of hydrogenolysis
    1-carbazolyl- (4) -oxy-3-N-benzyl-20 -2- (5-carbamoyl-2-pyridyloxy) ethylamino-propanol- (2).
    d) 1-carbazolyl- (4) -oxy J-3- 2- (2-hydroxyphenoxy) -ethylamino-propanol- (2). Exit 77% of theory, hydrochloride 25, m.p. 214-215 ° C, by hydrogenolysis of 1-carbazolyl- (4) -oxy-3- 2- (2-benzyloxyphenoxyl) ethylamino-propanol- (2).
    Example 9. 1-carbazolyl-30- (4) -oxy-3- 2- (5-fluoro-2-methoxyphenoxy) ethylamino-propanol- (2). 7 g 1-amino-3-carbazolyl- (4) -oxy-propanol- (2); 9.2 g of p-toluene sulfonic acid- 2- (5-fluoro-2-methoxy-35 phenoxy) ethyl ether and 3.8 ml of triethylamine are stirred in a medium of 20 ml of dimethylformamide for 20 hours while poured into a dilute solution of sodium hydroxide, - construct with methylene chloride, dry and purify by chromatography as in Example 4. After recrystallization from ethyl acetate, using activated charcoal and bleaching clay, 2.7 g of 45 (23% of theory) are obtained. Colorless crystals, so pl. 14b-147 ° C.
    The starting compounds are prepared as follows:
    1-amino-3-carbazolyl- (4) -oxy-50-propanol- (2).
    40 g of 4- (2,3-zpoxypropoxy) -carbazole are stirred in an autoclave with | 00 ml of liquid ammonia in 2 l of methanol for 24 hours at 50 ° C. After striking the bed and recrystallization from ethanol, yield 31 g of colorless crystals, pl. l4l-143c.
    H-toluenesulfonic-2- (5-fluoro 2-methoxyphenoxy) ethyl ester.
    40.4 g of 5-Fluoro-2 methoxyphenol; LO 24.6 ml of 2-chloroethanol and 20.7 g of potassium hydroxide in 100 ml of dimethyl formamide are stirred for 2 hours at 70 C. poured into water, extracted with methylene chloride, distilled off the residue after 65
    extract in a high vacuum to obtain 11.3 g of 2- (5-fluoro-2-methoxyphenoxy) ethanol. Colorless oil, hardening on standing. T. pl. 43-45 ° C. An additional exchange reaction with p-toluenesulfonic chloride gives tosylate, m.p. 6668С (from ethanol).
    权利要求:
    Claims (2)
    [1]
    1. A process for the preparation of carbazolyl- (4) -oxypropanolamine derivatives of the general formula
    o-cng-ck -sn-: -sn-cn-x- @ r
    about RjRs Jl4
    RI
    (i)
    where R is hydrogen, lower alkyl or aroyl;
    Hydrogen, lower alkyl or
    aralkyl; R} is hydrogen or lower alkyl;
    hydrogen or lower alkyl;
    —SND-, oxygen or sulfur,
    or simple communication;
    Ag mono - or bicyclic aryl
    or pyridine;
    R (, is the same or different, hydrogen, halogen, lower alkyl, aminocarbonyl, hydroxy, lower alkyl, alkoxy, aralkoxy, lower alkylsulfinyl, lower alkylsulfonyl, or methylenedioxy, together
    R HRj and when X is oxygen, together-CHj-O-, or their salts, about tl and h and y y. and and with the fact that the compound of the formula
    O-SNg-CH-SNg-
    about
    to;
    (but)
    where Y is halogen or sulphonate, and R has the meanings indicated for I, or Y and Ri (together, a simple bond, 1) react with a compound of the general formula
    (five)
    us-sk-ns-x
    I
    Ya RJ
    but-
    X, Ag,
    Rg- and Rf
    where is Rji, R
    R4:
    have
    Uh
    the indicated values and the target product are carried out in free form or in salt form.
    [2]
    2. A process for the preparation of carbazolyl- (4) -oxypropanolamine derivatives of the general formula
    (fH-CH-W-CH-CH-X-Q; R and-R R4
    O t 13 where R is hydrogen, lower alkyl or aroyl i Rj. hydrogen, lower alkyl or aralkyl; R is hydrogen or lower alkyl; R / j. Is hydrogen or lower alkyl; X is -CHj, -, oxygen or sulfur, or a simple bond; AH - Mono- or bicyclic aryl or pyridine; Rg. and the same or different hydrogen, halogen, lower alkyl, amino carbonyl, hydroxy group, lower alkoxy aralkoxy group, lower alylsulfyl NIL, lower alkylsulfonyl or methylenedioxy, and when X is oxygen, R / t and R ,; together - - CI-I2-0-, 9. or their salts, characterized in that the compound of the total formazh-l O-Sig-CH-CHg-ha. ; d- ,; R and .R; i 1 ;; -; e10Т is indicated as follows; and interactions1, with the coefficients of the general rmula Y-T-CH-CH-X- (AGG gg, R, R. ,, X, Ai, RR .. named. indicated:;)) acheia and target allocation in freedoms FOM and - , 1 in wil salt. Historical information; 1, h, taken in the examination 1. Buhler K., Pearson D, Organic Si1 -...- .., Y. , 1973, 1.1, p. 304,
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    同族专利:
    公开号 | 公开日
    ATA276279A|1984-01-15|
    JPS54157558A|1979-12-12|
    DD143607A5|1980-09-03|
    DK141979A|1979-10-14|
    DE2815926A1|1979-10-18|
    BG61419B2|1997-07-31|
    MX9203380A|1992-09-01|
    HU179433B|1982-10-28|
    NL930110I2|1994-12-01|
    HK2385A|1985-01-18|
    IL57020A|1982-07-30|
    FI70406B|1986-03-27|
    ES479396A1|1980-04-16|
    JPH0123462B2|1989-05-02|
    EP0004920B1|1981-08-05|
    NL930110I1|1993-10-18|
    CS227007B2|1984-04-16|
    IL57020D0|1979-07-25|
    EP0004920A1|1979-10-31|
    LU88320I2|1994-05-04|
    FI791142A|1979-10-14|
    AU522975B2|1982-07-08|
    JPS63258416A|1988-10-25|
    FI70406C|1986-09-19|
    US4503067A|1985-03-05|
    DE2960553D1|1981-11-05|
    DK154555B|1988-11-28|
    CS420091A3|1992-04-15|
    CA1129416A|1982-08-10|
    AT375639B|1984-08-27|
    SG52284G|1985-03-29|
    ZA791732B|1980-05-28|
    LT2628B|1994-04-25|
    DK154555C|1989-06-19|
    AU4582079A|1979-10-18|
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    法律状态:
    优先权:
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    DE19782815926|DE2815926A1|1978-04-13|1978-04-13|NEW CARBAZOLYL--OXY-PROPANOLAMINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS|
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