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    • 专利摘要:

    公开号:SU965356A3
    申请号:SU802930703
    申请日:1980-06-12
    公开日:1982-10-07
    发明作者:Хоровски Райнхард；Кер Вольфганг；Зауер Герхард；Эдер Ульрих；Петер Лоренц Ханс
    申请人:Шеринг Аг (Фирма)；
    IPC主号:
    专利说明:

    hydrogenated, isolated in free form or in the form of salts by known methods. To carry out the proposed process, in the first stage, the N-alkylated methyl esters of lysergic acid, by reacting them with anhydrous hydrazine, are converted into the corresponding hydrazides, without separating the resulting isomers. In the second stage, the hydrazide obtained by reacting it with nitrogen acid is converted into azide kilotypes, the aqueous solution of the reaction mixture is mixed with a buffer, for example sodium bicarbonate, monosubstituted sodium phosphate, sodium acetate with potassium borate or ammonia and extracted from it. toluene In the third stage, the toluene phase is heated to a temperature of from 70 ° C to the boiling point of the reaction mixture, as a result of which the corresponding isocyanate is formed. In the fourth stage, the isocyanate obtained is reacted at room temperature with diethylamine. A mixture of isomers of derivatives of N, N-diethylmochevine is formed, the separation of which into individual isomers is carried out using chromatography. In that case, if you want to get compounds with a saturated bond in the 9, 10-position, the resulting products in the previous step are hydrogenated in a known manner. Thus, for example, hydrogenation can be carried out with hydrogen in the presence of palladium on charcoal or another suitable carrier, for example lime, in the presence of platinum, for example, in the form of platinum black, or in the presence of nickel, for example, in the form of Rene nickel. After completion of the hydrogenation. purification of the obtained product or its separation into individual isomers follows by means of chromatography. The compounds thus obtained in the form of free bases or in the form of their acid addition salts. obtained by reacting them with a physiologically acceptable acid, such as tartaric, maleic or benzoic acid, is purified by recrystallization and / or chromatography. . In order to obtain salts, the compound obtained by the method described above is dissolved in a small amount of methanol and the resulting solvent is then mixed with a concentrated solution of the corresponding organic acid in methanol at room temperature. Unknown starting compounds may, for example, be obtained in the general case by following the recipe. Dissolve 1 mmol of 6-nor-lysergic acid methyl ester in 10 ml of dimethylformamide, nitromethane or acetonitrile, add 420 kg of anhydrous potassium carbonate (3 mmol) and 1.6 mmol of an alkylating agent, such as a halide, to the resulting solution and keep the mixture in for 1-8 h at temperatures up to 50 ° C. The solvent is then distilled off completely in vacuo, the residue is distributed between chloroform and water and the chloroform is extracted several times from the aqueous phase in a separatory funnel. The organic phases are washed with water, dried over magnesium sulfate and evaporated. The resulting crude product is an oily mixture of 8 isomers, quite suitable for use in the next step without further purification, the coloring impurities are removed from it by filtration through a layer of silicic acid. The IR spectra were taken in KBr-UV spectra — in methanol as a solvent, and the NMR spectra, if not specified, —in CDCl1. Example 1. 2.9 g of 6-nor-6-ethyl- (iso) -lycergic acid methyl ester is dissolved in 100 ml of anhydrous hydrazine and incubated obtained pacTBojp for one hour at 50 ° C. The reaction mixture is then cooled, diluted with 300 MP of chloroform and shaken with a separatory funnel with a saturated sodium chloride solution. The organic phase is dried and evaporated to give 3.1 g of 6-nor-6-ethyl- (iso-legeric acid hydrazide), which is a mixture of isomers, which, without purification, is dissolved in 50 ml of 0.2N. hydrochloric acid and mixed with ice cooling with 10 mp of 1 n sodium nitrite solution and 55 ml of 0.2 n hydrochloric acid. After 5 min, the mixture is distributed between toluene and sodium carbonate solution, and the water is re-extracted with toluene in a separatory funnel and dry the toluene extract with sodium sulfate. Then the toluene phase is pulled out The mixture is stirred for 15 minutes at 80 ° C and stirred for 1 hour at room temperature with 10 ml of distilled diethylamine. After evaporation, 3.8 g of 3- (9,10-di-dihydro-6-ethyl-8-ergolinyl) are obtained. -1, 1-diethyl urea, a mixture of isomers. To separate the mixture into individual isomers, it is subjected to chromatography on silica gel, using a mixture of methanol and chloroform as eluent. 1.2 g of the more mobile component, which represents is an isomer with a 8 O1 configuration, namely, 3 - (. 9, 10-di-dehydro-6-ethyl-8cA-ergolinyl; -1,1-diethylureas y
    IR: 3250, 1638, 1505 cm.
    , a7 (219 (157иО), 225 .U5700);
    241 (14800); 310 (6150). NMR: cG 1.11 (e ,, EN), 6.51 (t 1H),
    6.88 (t, 1H) 8.52 (s, 1H),
    The resulting compound is dissolved in a small amount of methanol and the solution is mixed with a concentrated solution of 0.6 g of maleic acid in methanol at room temperature. From the reaction mixture, 1.4 g of 3- (9,10-di-dehydro-6-ethyl-VIV-ergolinyl) -1,1-diethyl urea acidic salt crystals of maleic acid are isolated. , ,
    The less mobile component in the chromatographic separation is the conjugate BP-configuration (l, lj of the crude product), namely, 3- (9,10-DI-dehydro-6-. Ethyl-8 (5-ergolinyl) -1,1-diethyl urea .
    IR: 3240, 1625, 1510 cm :.
    UV: Lts x 241 (14200), 310 (6150).
    RMP- .cf (m, .1H), 6.87 (m, 1H), 8.36 (S, 1H).
    It is also dissolved in a small amount of methanol, mixed with a concentrated solution of 0.6 g of maleic acid and subjected to crystallization. The result is 1.0 g of acidic maleic acid 3- (9,10-di-dehydro-6-ethyl-8 (4-ergolinyl) -1,1-diethyl urea,
    L p m and m r 2. From 3.1 g of methyl 6-nor-6-n-propyl- (iso-yergic acid as the starting compound, hold it for one hour at room temperature with 100 ml of anhydrous hydrazine 3.2 g of 6-nor-6-n-propyl (iso) -li or zerginic acid hydrazide, which is a mixture of isomers, are obtained in the same post-treatment as in Example 1.The resulting hydrazide is further treated in the same way as and in Example 1. As a result, 3.2 g of -3- (9,10-di-dihydro-6-n-propyl-8-erginyl) -1,1-diethyl urea, which is a mixture of isomers, are obtained.
    The mixture obtained is separated into individual isomers by chromatography on silica gel using a mixture of methanol and chloroform as eluent. And in this case, the more mobile component is the 8c1-compound, namely 3- (9,10-di-dihydro-6-n-propyl-Vc-ergolinyl) -1,1-diethyl urea.
    IR: 3420, 1630, 1505 cm,
     216 (17900), 240 (16900), 310 (7140).
    NMR: about 6.54 (t, 1H), 6.88 (t, 1H), 7.97 (S, 1H).
    The resulting compound is dissolved in a small amount of methanol, the resulting solution is mixed with a solution of 0.5 g of ct-tartaric acid, and crystallization is carried out at 0 ° C. The result of 1.2 g of tartrate 3- (9,10-di-dehydro-6-n-propyl-8 A-ergolinyl) -1, 1-diethylurea,
    The less mobile component, which is 3- (9,10-di-dihydro-6-n-propyl-8 b-ergolinyl) -1,1-diethyl urea, in the same way, namely by reacting with 0.5 g of tartarone acids are converted to tartrate of 3- (9,10-di-dihydro-6-n-propyl-8/5-ergolinyl) 5 -1,1-diethyl urea,
    IR: 1614, 1525 cm
    NMR: (d-MeOH),, 02 (t, 1H),
    4.43 (t, 1H), 6.40 (t, 1H),. 7.03 (t, 1H).
    0 Example 3. In the same manner as described in Example 1, the corresponding 6-nor-6-iso-propyl (iso) hydrazide is obtained from 310 mg of 6-nor-6-isopropyl- (iso) -leggeric acid methyl ester α-lysergic acid, which is a mixture of isomers, with a yield of 290 mg, which is the same as in Example 1, is subjected to Subsequent transformations and processing, using Q and 1/10 of the quantities of reagents specified in Example 1. The resulting 335 mg of crude 3- (9,10-di-dehydro-6-from propyl-8-ergolinyl) -1,1-diethyl urea is separated by preparative column chromatography. More than 5, the mobile component (98 mg), by reaction with 50 mg of maleic acid, is converted to the acidic maleic acid 3- (9,10-di-dehydro-6-isopropyl-8 (L-ergolinyl) -1,1-diethyl moiety), which after crystallization, the crystals are precipitated.
    The less mobile component, which is 3- (9,10-d-dehydro-6-isopropyl-8 / l-ergolinyl) -1,1-di5 ethyl urea / is converted into methanesulfonic acid salt 3- (9, by reaction with methanesulfonic acid) 10-di-dihydro-6-isopropyl-8 / b-ergolinyl) -1,1-diethyl urea and make it in the form of Q crystals.
    Example 4, From a 324 mg methyl ester of 6-nor-b-n-butyl- (iso) -lesertic acid, the mixture of isomeric hydrazides is obtained as the starting compound according to the method described in example 3. 330 mg of crude b-nor-b-n-butyl- (iso) -l-ergic acid hydrazide is then converted, as described in Example 3, into a mixture of 3- (9,10-di-dihydro-60-n-butyl -8-ergolinyl) -1,1-di-urea, which is then separated into individual isomers by chromatography. By reacting with 50 mg of maleic acid from the more mobile component 3- (9,10-di-dehydro-6-n-butyl-8o1-ergolinyl) -1,1-diethyl urea, the acid salt of maleic acid 3- (9.10 di dihydro-b-and-butyl-8o1-ergolinyl) -1/1-diethyl urea (103 mg). IR: 3250, 1650, 1505. UV: Avnax 241 (17100), 310 (7130). NMR: 08 (t, Hz, 6H), 1.17 Tt, Hz, 3N), (W 1H), 6.93 (p, 1H), 8.28 (t, 1H). Component less mobile during chromatography, representations of a 3- (9 1p-di-dehydro-6-n-butyl-8/3-ergolinyl -1,1-diethylm chevine. IR: 3270, 1660, 1505 cm-, UV : Dgpah 219 (21300), 225 (21200), 241 (19500), 310 (8390) NMR: CO 6.36 (t, 1H), 6.93 (t, 1H), 8.20 (S, 1H) , when reacting its solution in methanol with tartaric acid, it gives 120 mg 3- (9,10-di-dihydro-6- - -Gytil-8 (-ergolinyl) -1,1-diethyl urea. Example 5. 1.0 g 3 - (- 9,10-di-dehydro-6-ethyl-8 (b-ergolinyl) -1,1-di-ethyl urea) is dissolved in 20 ml of methanol, 100 ml of palladium-carbon is added to the prepared diluent. hydrogenation at room temperature and normal This is followed by filtering, the solution is concentrated, and 2N phosphoric acid solution is added to it under visually acidic reaction. After recrystallization from methanol, 0.9 g of 3- (6-ethyl-8) phosphate is obtained. - air golin-1-yl) -1,1-diethyl urea. IR: 1620 cm - UFG 225 (27000), 285 (6200). Example 6. 1.0 g of 3- (9,10-dihydro-6- ethyl 8o (.-ergolinyl) -1,1-diethyl urea is dissolved in 30 ml of methanol, about 1 g of Rene nickel is added to the prepared solution, and hydrogenation is carried out at room temperature and hydrogen pressure. and 35 ati. The catalyst is filtered off, the solution is concentrated and after purification of the crude product by chromatography on silica gel using a mixture of chloroform and methanol as eluent, 0.5 g of 3- (6-ethyl-8o1-ergolin-1-yl) -1,1- is obtained. diethyl urea, {which by reaction with phosphoric acid is converted to the corresponding crystalline salt. After recrystallization from methanol, 0.4 g of phosphate 3- (6-ethyl-8 | A-ergo lin-1-yl) -1,1-diethyl urea were obtained. IR: 1620 cm. 223 (28000), 281 (6100), 292 (5450). For m-yo p 7.1.0 gz- (9, GO-di-dehydro-6-n-propyl-8 (b-ergolinyl) -1,1-diethyl urea, as described in example 5, is hydrogenated in environment and dioxane and subjected to subsequent processing, resulting in a gain of 0.8 g of tartrate of 3- (6-and-propyl-8 / a-ergolin-1-yl) -1,1-diethylurea. IR: 1620 cm. 225 (27000), 285 (6200). Example 8. 2.0 g of 3- (9,10-di-dehydro-6-n-propyl-8c1-ergolinyl) -1, 1-diethyl urea, as described in Example 6 is subjected to hydrogenation and subsequent processing, isolating the final product in the form of a salt of phosphoric acid. The result is 0.8 g of phosphate 3- (6-n-propyl 8ct-ergolin-1-yl) -1,1-diethyl urea. When tartaric acid is used, 3- (6.-n-propyl-8s | 1-ergolinyl) -1,1-diethyl urea tartrate is obtained. IR: 1620 cm- UV: No. 223 (28900), 281 (6400), 292 (5390). NMR: (d-Py): 0.88 (t, 3 7 Hz, ZN), 1, 12 (t, Hz, 6H ) 5.41 (t, 1H). 11.55 (S, 1H). EXAMPLE 9. 1.0 g 3- (9,10-didehydro-b-isopropyl-8/5-ergolinyl ) -1, 1-diethyl ureas are hydrogenated as described in Example 5, and by reacting the hydrogenation product with maleic acid, 0.8 g of the acid salt of maleic acid 3- (6-isopropyl-8 L-ergolin-1-yl) - 1,1-diethyl urea. Example 10. Hydrogenation is carried out with 1, 5 g of 3- (9,10-di-dihydro-6-isopropyl-8O1-ergolinyl) -1,1-diethyl urea in the same manner as described in Example 6, and the resulting 3- (6-isopropyl-8b. -ergolin-1-yl) -1,1-diethyl urea chromatography is converted to 3- (6-isopropyl-1-8oL-ergolin-l-yl -1,1 phosphate by reaction with phosphoric acid -diethyl urea. Yield 0.5 g. Example 11. 0.5 g of 3- (9,10-dehydro-6-n-butyl-8 (ergolinyl) -1, 1-diethyl urea is hydrogenated and converted into salt by the method described in example 5. Yield 0.5 g of 3- (6-n-butyl-8 (L-ergolin-1-yl) -1,1-diethylurea. IR: 1625 cm-H. At : 1625 cm-, Atah 225 (26500), 286 (6100). Example 12. 1.5 g of 3- (9,10-di-dehydro-6-n-butyl-8o-ergolinyl) -1, 1-diethyl urea subjected to hydrogenation and then get the crystalline salt according to the method described in example 6. The output of 0.6 g of phosphate 3- (and-butyl-8O1.-ergolin-1-yl) -1,1-diethylurea. IR: 1620 cm. UV : Lts1x 223 (28000), 280 (6200), 292 (5400). Example 13. Generally, compounds are prepared according to the following recipe. 10 mmol methyl ester of m-alkyl-lysergic acid (mixtures of isomers) as the starting material is dissolved in 100 ml of anhydrous hydrazine and kept the solution for 16 hours at. The reaction mixture is then cooled, diluted with 300 ml of chloroform, and extraction is carried out from it in a separatory funnel with a saturated solution of sodium chloride. The organic phase and leave. The resulting hydrazide is a mixture of isomers. It can be used without additional purification as a starting product in the next stage. ,, 1 g of the hydrazide obtained in this way is dissolved in 10 ml of tetrahydrofuran, and the resulting solution is mixed with ice-cooling with 12 ml of 1N. After stirring for 10 minutes, 3.6 ml of a 1 M solution of sodium nitrite and 7.2 ml of 1N are added to the reaction mixture. hydrochloric acid and continue stirring in an ice bath for another 10 minutes. 100 m of toluene is added to the mixture, 50 ml of saturated sodium carbonate solution is added dropwise with vigorous stirring, and the organic phase is separated. From the aqueous phase, extraction is carried out twice in a separating funnel with toluene in 50 ml portions, all organic extracts are dried, combined and incubated for 15 minutes in an argon atmosphere in a bath at 100 ° C. The solution is then cooled to room temperature, mixed with 3 ml of diethylamine and the resulting mixture is stirred for one hour at room temperature. After evaporation of the reaction mixture, 3- (9,10-di-dehydro-6-C1-L-8-ergolinyl) -, 1-diethyl urea is obtained in the form of a mixture of isomers. Silica gel chromatography is used to separate it into individual isomers. A mixture of methanol and carbon tetrachloride is used as eluent; . The more mobile component is the 8oL connection, the less mobile component is the 8p connection. By the procedure described, the following compounds were prepared. 3- (9,10-di-dehydro-6-) 2-propen-1-yl (-vY-ergolinyl-1,1-diethylurea, OUTPUT 52% of theoretical. IR: 3300.1630, 1505 cm. UV : Yat „с.ч 216 (17000V 241 (15100), 310 (6900). NMR :(, 55 (t, 1H), 6.90 (t, 1H), 8.20 (S, 1H). 3- (9,10-di-dihydro-6) 2-propen-1-yl / -8p-ergolinyl) -1,1-diethylurea, yield 15% of theoretical. IR: 3300, 1625, 1505 cm. UV: Ap1s1X 241 (16500), 310-1 (6500). NMR: about 6.43 (t, 1H), 6.92 (t, 1H), 8.05 (S, 1H). Using methyl ether 9 as the starting compound, 10-di-dihydro-6- (2-propen-1-yl) -ergolin-8-carboxylic acid. IR: 3405, 1730. NMR: about "33.78 (S, 3N /, respectively 3.85 / S , ZN), 6.61 (t, HI), 6.92 (m, 1H), 8.07 / S, IN). 3- (9,10-di-dehydro-6- ( 2-propyn-1-yl) -8in1-ergolinyl) -1,1-diethyl urea, yield 48%. IR: 3250, 1638, 1505 cm, UV: A max 24-0 (14000), 310 (5900), NMR: (/ 6.50 (t, 1H), 6.90 (t, 1H), 8.10 (S, 1H) and d- / 9,10-di-dihydro-6- / 2-propyl-1 -yl / 8 (3-ergolinyl / -1,1-diethylurea, yield 15%. IR: 3250, 1650, 1510. UV: Lp, ah 219 (21000)., 225 (20800), 241 (18800) -, 310 (8100) (using 9,10-di-dehydro-6- (2-propyn-1-yl) -ergoline-8-carboxylic acid methyl ester as the starting compound). IR: 3410, 1725 cm ЯKP.d 3, 73 (S, 3H), respectively 3.81 (S, 3fl), 6.57 (t, 1H), 6.90 (t, 1H), 7.98 (t, 1H): ethyl 3- (9,10-di-dehydro-8c1- (3,3-diethylureido) -6-ergoline) -propioic acid ester, yield 36%. IR: 3290, 1655, 1505 cm. 240 (18000), 310 (7500) 3- / 9,10-di-dehydro-8d- / 3, 3-diethylureido / -6-ergoline / -propionic acid ethyl ester, yield 15%. IR: 3270, 1650, 1510 cm 241 (16900), 310 (6000). (when 3- / 9, 10-di-dehydro-8-methoxycarbonyl-6-ergOLIN / -PROPIONIC acid ethyl ester is used as the starting compound. IR: 3405, 1780 cm. UV: Antia 222 (20600); 309 ( 6700). Ya., 33 (t, Hz, ZN), 3.75 (S, ZN), respectively 3.82 "(S, ZN), 6.75 (t, 1H), 6.92 (t, 1H), 7.97 (S, 1H) ethyl ester of 3- (8OOO- / 3, 3-diethylureido / -6t-ergolin / -propionic acid, yield 45%. IR: 16.25 cM-t. 225 (26500) , 281 (5500), 290 (5200). NMR: f 6.92 (m, 1H), 8., 30 (S, 1H), and 3-l8 ethyl ester (i- (3,3-diethylureido / -6 Ergolin-propionic acid, yield .72%. IR: 3300, 1630 cm - UV: Yag, ah 224 (25000), 285 (5800), 3- / 9,10 g-di-dihydro-8-1-3 / 3, 3-diethylureido / -6-ergoli n-propionitr l, 43% yield. IR: 3420, 2245, 1630, 1505 cm. UV-Ltats 220 (21000), 307 (7100). NMR: oA - 6.54 (t, 1H), 6.95 (t, 1H), 8.10 (S, 1H) and 3- (9,10-di-dehydro-8 {- / 3, 3-diethylureido / -6-ergoline / -prodHOHHTpnnj yield 19%.
    IR: 3400, .2250, 1640, 1505 cm-.
    UV: Dpla 223 (20100), 310 (7000) (using 6- (2-cyanoethyl) -9,10-di-dihydro-ergoline-8-carboxylic acid methyl ester as the starting compound).
    IR: 3410, 2250, 1730 CM.
    UV: D№S17S 223 (22000), 307 (7350)
    NMR: / 3.72 (S, ZN), respectively 3.80 (S, 3H), 6.51 (m, 1H), 6.87 (m, 1H), 7.95 (S, 1H); Zg / 6-cyclopropyl-9, U-di-dehydro-ZoS-: ergolinyl / -1, 1-diethylurea, yield 35%.
    IR: 3250, 1635, 1505.
      218 (18300), 241 (16900 310 (6500), and 3- / 6-cyclopropyl-9,10-di-dehydro-8 (L-ergolinyl / -1.1 diethylurea, yield 18%.
    IR: 3250, 1630, 1505 cm. UV: Lts (X 242 (17000) 310 (6300) (using 6-cyclopropyl-9, 10-di-dihydro-ergoline-8-carboxylic acid methyl ester as the starting compound)
    IR: 3400, 1735 cm.
    UV: Atah 225 (20500), 230 (19100 310 - (7900),
    NMR: about 3.79 (S, 3N), 6.55 (t, 1H) 6.90 (t, 1H), 8.10 (S, 1H); 3- / 6-cyclopropyl -8c-ergolinyl / -1,1-diethyl urea, yield 40%.
    IR: 3350, 1620 cm--
    UV: Ltos (X 224 (26000), 281 (6200) 292 (5200) and 3- (6-cyclopropyl-8 b-ergolinil / -1, 1-diethyl urea, yield 68%.
    IR: 3300, 1615 cm-.
    UV: ATS (to 225 (27000), 283 (5800), 295 (5100);
    3- / 6-cyclobutyl-9,10-di-dehydro-8c - ergolinyl / -, 1-diethylurea, high yielding 39%.
    IR: 3350, 1640, 1505 cm-1.
    UV: Dts.x 219 (19400), 241 (17000) 310 (7050) and 3- / 6-cyclobutyl-: 9,10-di-dehydro-8 1-ergolinyl / -1, 1-diethylurea, yield 13% .
    IR: 3250, 1640, 1510 cm-g
    UV: Lts l 241 (14300), 310 (6150) (using 6-cyclobutyl-9, 10-di-dihydro-ergoline-carboxylic acid methyl ester as the starting compound).
    i IR: 3300, 1740 cm.
    UV: Ltah 227 (21000), 240 (17300) 310 (6900).
     NMR: c / 3.70 (S, ZN), respectively 3.78 (5, ZN), 6.57 (t, 1H), 6.87 (t, 1H), 8.05 (S, 1H); , 3- / 6-cyclopropyl-methyl / -9,10-di-dihydrog8 (1-ergolinyl / -1,1-diethylurea, yield 40%.
    IR: 3220, 1630, 1505.
    UV: LPShH 216 (17800), 240 (16900), 310 (7040).
    3- / 6-cyclopropyl / -methyl / 9,10-di-dehydro-8-ergolinyl / -1, 1-diethylurea.
    IR: 3280, 1630, 1505 cm.
    UV: Ltar 219 (21,200;, 225 (21,100) 241 a9500), 310 (8100) When using 6- / cyclopropyl-methyl / -9, 10-di-dihydro-ergoline-8-carboxylic acid as the starting compound ). .IR: 3270, 1740.
     226 (19500J, 240 tt7100) 310 (7050).
    The compounds of general formula I have pronounced dopamine activity. At the same time, in their action they are superior to luzirid hydromaleate.
    权利要求:
    Claims (1)
    [1]
    1. The method of obtaining derivatives (ergolinyl) - N, N-diethyl urea of the general formula I
    H-CO-H () g
    III
    N-r
    where R is alkyl C2-C4 or -CH-CH-CH ,; —CHj — C CH, (CH) —COOC H,
    (CH „)
    (sn2) „- sns :; /
    sleep where m is O or 1, and p 1 or 2,
     - means carbon carbon single or double bond, and the urea residue in the 8th position can be in the - or / j-position or their salts, characterized in that the N - alkyl ester of lysergic acid is converted to hydrazide by interaction with hydrazine, after which the resulting hydrazide is treated with nitrous acid to obtain azide, which is then converted into isocyanate by heating, followed by treatment with diethylamine and the resulting desired product, 9,10-double bond of which can be hydrated Ana is isolated in free form or as salts.
    Priority signs: 13.06.79 with R-alkyl C2-C4. 28.04.80 at 13965356 14 (CH) СООС2Н5, where m-0 or 1 or 2. rCHj-CH CHj, Information sources, -CHj-CsCH, taken into account during the examination - {CH2), 1. Patent of the Federal Republic of Germany 2238540, ČSN) „- CH, s /. cl. C 07 L 457/12, bpublik. CH7.1977.
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    同族专利:
    公开号 | 公开日
    IE49991B1|1986-01-22|
    ES8101073A1|1980-12-16|
    US4379790A|1983-04-12|
    DE3063869D1|1983-07-28|
    DK252680A|1980-12-14|
    EP0021206B1|1983-06-22|
    EP0021206A1|1981-01-07|
    HU184786B|1984-10-29|
    YU154480A|1983-09-30|
    DK149059C|1986-07-14|
    IL60261D0|1980-09-16|
    AU5913580A|1980-12-18|
    YU41929B|1988-02-29|
    CS223809B2|1983-11-25|
    ES492400A0|1980-12-16|
    IE801210L|1980-12-13|
    DK149059B|1986-01-06|
    IL60261A|1983-10-31|
    AU541679B2|1985-01-17|
    DD151449A5|1981-10-21|
    CA1140922A|1983-02-08|
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    法律状态:
    优先权:
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