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    • 专利摘要:
    A METHOD FOR OBTAINING DERIVATIVES 1-BENZOSH1-3- (ARYLPYRIDIL) UREADS OF THE GENERAL FORMULA O О Im C-SH-C-SH-RZ, I Oa that both radicals do not simultaneously mean a hydrogen atom, and also under the condition that one of the radicals R is a fluorine atom or methoxy, the other radical R cannot be hydrogen; n is an integer from 0 to 1; RI is independently chlorine or methyl; m is an integer from 1 to 2; Rj is the phenyl radical of the general formula where R% is a bromine, chlorine, fluorine or CF atom, J for R is methyl or methoxy, provided that the phenyl radical contains no more than two different substituents and the substituents on the pyridine ring are in the following positions x: a) the NH group with respect to the pyridine nucleus is in the second position of the ring, the R group is in the fifth position of the pyridine ring, and if m is 1-2, any substitute is in the fourth, sixth or fourth and sixth positions pyridine ring, except when where R is a chlorine atom, is in the sixth position of the core and 1-1; if tn and p O and each of R is methoxy, RJ is unsubstituted phenyl, 3-chlorophenyl, 3,4-dichlorophenyl, or A-me-hydroxyphenyl; if m and n O and each of R is methyl, RI is not 4-chlorophenyl}
    公开号:SU1158043A3
    申请号:SU823404595
    申请日:1982-03-02
    公开日:1985-05-23
    发明作者:Луис Мисель Джон
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    if m and n O, and one of R is a chlorine atom, and the other is a hydrogen atom, Rj. not 3-chlorophenyl, 3,4-dichlorophenyl, 4-tolyl, 4-methoxyphenyl; if one of R is a chlorine atom and the other is R is a hydrogen atom, Rj is not 3-chlorophenyl, 3,4-dichlorophenyl, 4-tolyl or 4-methoxypheyl} if m 2 and n O, one of R is methyl, the other R, not a chlorine atom; if n is 1, none of R is methyl or methoxy, any of R is Mb type or chlorine atom, and Rj is chlorine atom, Rj. - phenyl, in the para-position substituted by a bromine, chlorine or fluorine atom, methyl, or CF,; if n 1 and one of R is a hydrogen atom, m 1-2; or b) the NH group with respect to the pyridine ring is in the third position of the core, the Rj group. is in the sixth position of the pyridine ring, and if m 1 any of the substituents R4 is in the fifth position of the pyridine ring, except for compounds in which m is 0-1 if n O, RV is methyl, if n O, one of R is methyl, and the other is a hydrogen atom, Rj. is not unsubstituted phenyl-. 1158043 e chlorine vapor para chlorine from benzo where subfamine where and when n 1, each of R is an atom of a or fluorine, RI is methyl and Rj. -substituted phenyl by a bromine atom, or a fluorine atom, methyl, which is characterized by the fact that the strong derivative of the general formula CNCO R has the indicated values, interacts with the production of pyridine of the general formula H2N-fB-I 2 Freedom are available.
    The invention relates to methods for the preparation of 1-benzoyl-3- (arshylpyrvd1) urea derivatives of the general formula R 0 (O C-W-C-W- (Re, R where kazvdy from R is a hydrogen, bromine, chlorine or fluorine atom, or methoxy, provided that both radicals do not simultaneously mean a hydrogen atom, and also provided that when one of R is a fluorine atom or methoxy, the other R is not hydrogen and n is an integer from O to 1 i-. Rf - independently Sign4keT chlorine atom or methyli m is an integer from 1 to 2; Rj is a phenyl radical of the general formula where Rj is a bromine, chlorine, fluorine or CFj atom; R4. is methyl or methoxy, provided that the phenyl radical contains no more than two different substituents, and the substituents in the pyridine ring are in the following positions; a) the NH group relative to the pyridine core is in the second position of the ring, the Rj group is in the fifth position of the pyridine ring, if m 1- 2, any substitute is in the fourth, sixth or fourth and sixth positions of the pyridine ring, except when RI is a chlorine atom, is in the sixth position of the core and m 1- if m and n O and each of R is: methoxy, R - phenyl unsubstituted, 3-chlorof nyl, 3,4-dichlorophenyl or 4-methoxyphenyl; if m and p O and each of R is methyl, Ri is not 4-chlorophenyl; if m and n O, and one of R is a chlorine atom, and the other is a hydrogen atom, Rj is not 3-chlorophenyl, 3,4-dichlorophenyl, 4-tolyl, 4-methoxyphenyl; if m 2 and n O, one of R is a chlorine atom and the other is a hydrogen atom, RJ is not 3-chlorophenyl, 3,4-dichlorophenyl, 4-tolyl or 4-methoxyphenyl; . if m 2 and n O, one of R, methyl, and the other R is not a chlorine atom; if n is 1, none of R is methyl or methoxy, any of R is methyl or chlorine, and Rj is phenyl, in the para-position substituted by a bromine, chlorine or fluorine atom, methyl and CFj i if n 1 and one of R is a hydrogen atom, m 1-2, b) the NH group relative to the pyride of the new ring is in the third position of the core, the RI group is in the sixth position of the pyridine ring, and if m 1, any of the substituents RI is the FOUR position of the pyridine ring, except for compounds in which m 0-1, if n O, R, is methyl, e if n O, one of R - methyl, and the other - a hydrogen atom Rj is not unsubstituted phenyl; if h, 1, each of R doesn’t record a chlorine or fluorine atom from each other; 1 - methyl-, R, - para-substitutional fennp, bromine, chlorine or fluorine atom, methylene, which can be used as a useful substance in an agricultural host. The interaction of isocyanates with amines 1 is known. As a rule, the reaction is carried out in an organic solvent, such as a hydrocarbon, halohydrocarbon, ethyl acetate or acetonitrile at a temperature from 0 ° C to a boiling point of the solvent, preferably at room temperature Q2. The closest in structure, analogue is 1- (2,6-difluorobenzoyl) -3- (4-chlorofensh1) urea (Diflyubensuron), which has insecticidal properties. The purpose of the invention is to develop a method based on the known method of obtaining new derivatives of 1-benzoyl 3- (arylpyridyl) urea with insecticidal properties. This goal is achieved by the method of obtaining 1-benzoyl-3- (arylpyridyl) urea derivatives of the general formula I, which consists in the fact that the benzoyl derivative of the general formula where R has the indicated meanings is reacted with the Hirs of pyrschine of the general formula (2, where RI, Rj. , the type has the indicated values, and the desired product is given in free form. The starting compounds of the general formulas 1 and iM are obtained by limestone methods. to 138 g of phosphorus oxychloride, Keeping the temperature of the reaction mass 20-30 With external cooling.
    The mixture is stirred for
    15 min at room temperature with the Subsequent addition to it of 50 g of 4-chlorofenes acetic acid in 30 ml of DMF. After soaking at 65-75 C for 20 h, the reaction mixture is cooled, poured into 1 kg of ice and alkalinized to pH 12 by the addition of 50% sodium hydroxide with subsequent concentration at elevated temperature over a steam bath
    1 h. The precipitate formed is filtered off and then recrystallized from ethyl acetate, whereby the desired product is obtained from T.Sh1. 117-120 ° C.
    Example 2. 5- (4-Chlorophenyl) -3-cyano-2 (1H) -pyridone ..
    7 g of sodium in 300 ml of methanol is stirred with the simultaneous addition of a methanol solution
    16g 2-cyanoacetamide and 37 g 2- (4-chlorofensh1) -3- (dimethylamino) -acrolein. The mixture was then stirred for 1 hour at reflux temperature, and the precipitate formed was filtered, washed with ethanol, dissolved in hot water and then acidified. Formed
    The precipitate is filtered off, washed with water. Identify it as a degradable product with mp. 278-280 C.
    Example 3. 2-Chloro-5- (4-chlorophenyl) -3-pyridinecarbonitrile ..
    A mixture of 2.0 g of 3-cyano-5- (4-chlorophenyl-2- (1H) -pyridone with 3.8 g of phenylphosphidichloride is kept for 4 hours at an oil bath at 175 C. by adding ammonium hydroxide with stirring. The resulting brownish solid is used without further purification (2.0 g, mp. t85-l87c).
    I.
    Example 4. 2-Amino-5- (4-chlorophenyl) -3-pyridinecarbonitrile.
    A solution of 2.0 g of 2-chloro-5- (4-chlorophenyl) -3-pyridinecarbonitrile in 30 ml of DMSO is maintained on an oil bath at 80-90 ° Cj and then treated with ammonia for 2.5 hours. The reaction mixture then stands at room temperature for about 60 hours, followed by
    adding an additional 5 g of the starting reagent to 35 ml of DMSO. Then the mixture at 80-90 ° C for about 28 hours is treated with ammonia, after which it is poured into a mixture of ice water. The resulting tan solid brown precipitate is filtered out in an amount of 5.5 g with a mp. C and used in the future without prior purification.
    Example 5. 2-lmino-5- (4-chlorophenyl) -3-pyridinecarboxylic acid.
    2.0 g of 2-amino-5- (4-chlorophenip) -3-pyridinecarbonitrile in 25 ml of 50% sulfuric acid is held at reflux temperature for 24 hours. The acidified solution is poured into a mixture of ice-water to obtain 2.7 g of a solid yellow precipitate, which is filtered and using NMR spectrograms and identified as the target product
    The synthesis of the target product can also be carried out by alkaline hydrolysis. For this, 2.0 g of 2-amino-5- (4-chlorophenyl) -3-pyrvin dinocarbonitrile and 2.0 g of potassium hydroxide in 30 MJi of ethylene glycol are kept in an oil bath at 150 C. the alkaline solution is poured into a mixture of water and ice, followed by acidification, resulting in the obtained target product. The final product is again identified by means of NMR spectrogram MM1 (yield 2.3 g, mp 300-315 ° C, decomp.).
    Example 6, 5- (4-Chlorophenyl) -2-pyridipamine.
    1.0 g of 2-amino-5- (4-chlorofensh1) -3-pyridinecarboxylic acid, 0.2 g of powdered copper and 10 ml of quinoline are held in an oil bath at 205 ° C. After 2.5 hours, the temperature is raised to an additional hour. As a result, a solid precipitate is formed, which is collected and then washed with ethyl acetate. Then the solution is separated and the precipitate is subjected to chromatography on 300 ml of silica gel. The gummy solid was introduced into the top of the column with diethyl ether, followed by elution with an additional amount of diethyl ether until the quinoline was completely removed. As a result of elution with ethyl acetate, a very short cured brown solid was obtained which recrystallized from a mixture of methanol and water, in the result of which 400 mg of tan brown flat crystals with m.p. 122-1244. Calculated,%: C 24.56; H A, 43; N 13.69. Found,%: C 24.48; H 4.33; .N 13.99. Example 7. 1- (2,6-Dichlorobenzoyl) (4-chlorophenyl) -2-pyridyl-urea. At room temperature, between 0.6 g of 5- (4-chlorophenyl) -2-pyridylamine and 0.8 g of 2,6-dichlorobenzoyl isocyanate is reacted with a small amount of dichloromethane. A somewhat exometric reaction is accompanied by an almost immediate precipitate precipitate. After 3 hours at room temperature, the reaction mixture is cooled in an ice bath and then filtered to obtain 770 mg of colorless crystals. The identity of this product with so pl. 230-233 C is confirmed by NMR spectrogram, product yield 62.4%. Calculated,%: C 54.25; H 2.88, N 9.99. Found,%: C 54.28; H 3.00; N 10.23. Example 8, 1- (2,6-Dimethox benzoyl) -3- 5- (4-chlorophenyl) -2-pyridyl-3-urea. The reaction between 0.6 g of 5- (4-chlorophenyl) -2-pyridylamine and 0.8 g of 2,6-dimethoxybenzoyl isocyanate is carried out in a small amount of dichloromethane for 2 hours at room temperature. This reaction is also somewhat exothermic, but is not accompanied by precipitate deposition. Next, the mixture is boiled for 30 minutes with a reflux condenser, cooled to. room temperature and separated. The resulting crude solid is recrystallized from approximately 50 ml of ethanol, resulting in 780 mg of needle-like crystals. The identity of the final product with so pl. A 205-215 ° C is confirmed by an NMR spectrogram, the yield of 64.6%. Calculated,%: C, 21.24; H 4.41; N fo, 20. Found,%: C 20.99; H 4.24; N 10.01. 438 Example 9. 1- (2-Chlorbenoyl) -3-5- (4-chlorophenyl) -2-pyridnl} -urea. A reaction is carried out between 0.6 g of 5- (4-chlorophenyl) -2-pyridylamine and 0.7 g of 2-chlorobenzoyl isocyanate in accordance with Example 7. The identity of the product, the yield of which is 920 mg, and so forth. 228-231 ° C, confirmed by NMR spectrogram, product yield 81.3%. Calculated,%: C 59.09; H 3.39; N 10.88. Found,%: C 58.83; H 3.12; N 10.64. EXAMPLE 10 N-f2- (4-chlorophenyl) -3- (dimethylamino) -2-propenylidene-N-fetiamethanamine peroxide. 219 g of DMF with constant stirring and using an ice bath to maintain the temperature in the range of 27-30 ° C are added dropwise to 162 ML of phosphorus oxychloride. This mixture was stirred at room temperature for 45 minutes, 102.3 g of 4-chlorophenylacetic acid was added thereto, after which the mixture was held in an oil bath at 80-90 ° C for 3 hours. After stirring for about 18 hours The reaction mixture is extracted on ice using an ice bath to maintain the temperature close to room temperature. With vigorous stirring, solid NaClO. Monohydrate is added, resulting in a solid product, which is filtered off, washed with 15% NaClO. Solution, dried in air and recrystallized from boiling ethanol (product yield 170.3 g, m.p. 142-146 ° C). TI p and m 11. 11. 2-Amino-5- (4-chlorophenyl) -3-pyridinecarbonitrile. , in 16.2 g of sodium methoxide in 300 ml of meta-Thol and 19.8 g of malone, itaryl in 50-100 ml of methanol at 0 ° C in a bath of an alcohol-ice mixture is added to 101.1 g of (4-chlorophenyl) -3 - (dimethylamino) -2-propenylidene -N-methylmethamine perhylochlorate in 300 ml of pyridine. The reaction mixture is stirred at room temperature for approximately 20 hours, after which it is cooled again to. 120 ml of ammonium hydroxide are added to it. After 3 hours a heavy precipitate forms. This solid precipitate is filtered off, washed with water and using the NMR spectrogram, it is determined that this is the target product (yield: 44 g, mp 202-204 ° С). As a result of adding 600-800 ml of water to the filtrate, an additional amount of product is obtained, although it contains impurities. Example 12. 5- (4-Chlorophenyl) -2-pyridylamine. In accordance with examples 5 and 6, the conversion of 5- (4-chlorophenyl) -2-amino-3-pyridinecarbonitrile is carried out to the desired product. The identity of this product is confirmed by NMR analysis. For example 13. 1- (2,6-Difluorobenzoyl) -3-G5- (4-chlorophene) -2-pyridyl-urea. 2 g of 5- (4-chlorophenyl) -2-pyridylamine is dissolved in 90 ml of acetonitrile, followed by carrying out the reaction in a nitrogen zone at room temperature with 2.6 g of 2,6-difluorobenzoyl isotope. A solid product is formed immediately, which, after peremetana for about 15 hours, collected and using NMR analysis and identified as the target product (yield 3.4 g, so pl. 229-234s), the yield of the product 88,0%. Calculated,%: G 58.85; H 3.12 N, 10.84. Found,%: C 58.70-, H 3, N 10.92. Example 14. 5- (Dimethylamino) -4-fensh1-2,4-pentadiene nitrile. 5.64 g of trimethylsilypacetonitrile in 10 ml of THF at a temperature of from -68 to -70 ° C are added to 20.6 ml of H-BSTYLYLIA in 20 ml of THF. A bath of dry ice / acetone is used to maintain this temperature for approximately 45 minutes after the addition operation. Then the reaction mixture is heated to a temperature of about -40 ° C and a solution of 15 g of vinidomine salt (similar to that specified in Example 10 in 40 ml of pyridine) is added dropwise to it, maintaining the temperature in the range of approximately -45 to -40 ° C. After about 1 hour, the reaction mixture is heated to room temperature, and the solid product that forms during the addition process goes into solution. The mixture is then stirred for 20 hours. After removing the solvent from it in vacuo, a thick oil-like mixture is formed. The product is dissolved in ethyl acetate. The resulting organic layer is washed several times with water, then with saturated sodium chloride solution and dried under vacuum to give an oil-like product that crystallizes. This crystallized product is recrystallized from ethanol and identified by NMR spectral analysis as the desired product (yield - 5.4 g, mp 75-81 ° C). Calculated,%: C 78.75-, H 7.12; N 14.19. Found,%: C 77.27; H 7.41; N 13.72. A small amount of the material is recrystallized from ethanol. 81-83 C. Found,%: C 78.52; H 6.92; N 13.86. Another procedure for obtaining the desired product is also carried out. To a solution of 11.3 ml of n-butyl lithium in 75 ml of THF in a bath of dry ice / acetone was added 2.58 g of diisoprostamin. After stirring for about 10 minutes, 1.02 g of acetonitrile in 25 ml of THF is added, maintaining the temperature at about -70 ° C. The reaction mixture is stirred for about 40-50 minutes at -78 ° C, and then 7.5 g of the vinamidine salt in 20 ml of pyridine is added to it. Prior to addition, the temperature is increased to -45 ° C, after which it is kept in the range from -45 to -40 ° C until the addition operation is completed. Then the reaction mixture is stirred at a temperature of approximately -45 ° C for 1 h, left to warm to and stir it for an additional 18 hours. The solvent is removed to give an oil-like product, which is dissolved in ethyl acetate. The organic layer is washed several times with water, then with saturated sodium chloride solution, and finally dried in vacuum to obtain an oil-like residue that hardens. This solid product is recrystallized from ethanol (yield-1.5 g, t, units, 77-83 C), Example 15. 5-Phen l-2-1 Shridylamin. . Ammonia bubbles are passed through a layer of 50 ml of DMSO for approximately 0.5 hours and then 3.0 g of 5- (dimethylamine) -4-fenst-2,4-pentadienenitrile is added. This reaction mixture is gradually heated to 110.degree. C. at this temperature for about L2 hours, followed by pouring ice-water into the mixture and extraction with ethyl acetate. Diode emulsion decomposition agent was used after diethyl ether, after which 2-3 extraction treatments with chloroform were carried out. Both portions are dried under vacuum, and as a result, 1.1 g of crude semi-solid from the ether portion and 2.3 g of crude semi-solid from the chloroform portion are obtained. Chromatographic treatment of the extractable diethyl ether fraction on a silica gel using ethyl acetate as eluent yields approximately 300 mg of the final product, mp 129-132 ° C. Calculated,% C 77.6; H 5.92; N 16.46. Found,%: C 77.38; H 6.10; N 19.25. Example 16. 1- (2,6-Dichlorbe zoyl) -3- (5-fench1-2-pyridsh1) -ureas. 1.5 g of 2,6-dichlbrbenzoyl isocyanate in a small amount of dichloromethane are added to a solution of 1.0 g of 5-phenyl-2-pyridamine in 15 ml of dichloromethane. After boiling for about 5 minutes, a precipitate forms. After that, the reaction mixture is stirred at room temperature, then cooled, the precipitate is filtered off and recrystallized from ethanol to obtain 1.8 g of product. The identity of the final product was confirmed by NMR spectral analysis (mp. 221–23 G), the yield was 79.3%. Calculated,%: C 59.09; H 3.39; N 10.88. Found,%: C 58,; 95; H 3.47-, N 10.83. Example 17. 1-Methyl-2-phenylethylidenepropanedinitrile. 66 g of malononitrile, 134 g of phenylacetone, 8 g of ammonium acetate and 24 ml of glacial acetic acid are boiled in 400 ml of benzene for about 2 hours with a reflux condenser. Water is added, and then the benzene layer is rototed several times, dried and distilled off in vacuo to obtain an oil-like product. Thin-layer chromatographic analysis (diethyl ether) of this oil-like product gives one main spot, showing insignificant content of several impurities. The identity of the oil-like product as the target compound was confirmed by NMR spectral analysis. Example 18. 3,3-Diethoxy-1-methyl-2-phenylpropylidenepropanedinitrile. 9 t of 1-methyl-2-phenylethylidenepropanedinitrile are treated with 45 ml of triethyl orthoformate and 5 drops of borfluoride ether salt in an oil bath at 140-150 ° C for approximately 18 hours. The reaction mixture is refluxed for approximately 4 hours, and 10 ml of triethyl orthoformate and a few drops of boron trifluoride salt of ether are then added to it. The mixture is then reheated, separated off by distilling off the light fractions, and after dichloromethane is added to it, the light fractions are again distilled off, resulting in a residue in the form of a crude final product. Example 19. 3,3-Dimethoxy-1-methyl-2-fench 1 Propylidene propanedinitrile. The desired product is obtained in accordance with Example 18, except that trimethyl orthoformate is not used as the starting reagent, but trimethyl orthoformate. Example 20. A mixture of 2-amino-4-methyl-5-phenyl-3-pyridinecarbonitrile with 2-amino-6-metip-5-phenyl-3-pyridinecarbonitrile. At room temperature, 40 ml of ammonium hydroxide are added dropwise to 7 g of 3,3-dimethoxy-1-m-2-phenylpropyl-, propanedinitrile in 350 ml of THF. After stirring the reaction mixture for about 18 hours, an additional 10 ml of ammonium hydroxide is added to it. After about 24 hours, the light fractions are distilled off from the mixture, resulting in a dark dark crude product, which is chromatographed on 300 ml of silica gel using dichloromethane and a mixture of dichloromethane with 50% ethyl acetate as eluents. The crude product is then recrystallized from methanol to give gray needles of 5 similar crystals, which, as determined by NMR spectral analysis, contain approximately 60% of 4 methylene and approximately 40% of 6-methyl isomers (yield: 4.95 g, mp. 156-159 ° C). °
    Calculated,%: C, 74.64; And 5.26; N 20.10.
    Found,%: C 74.41; H 5.23; N 20.35.,. Example 21 A mixture of 2-amino-4 methyl-5-phenyl-3-pyridinecarbonitrile with 2-amino-6-metsh1-5-fensh1-3-pyridinecarbonitrile (another procedure).
    20 ml of ammonium hydroxide is added dropwise at room temperature to a mixture of 4.1 g of 3,3-diethoxy-1-methyl-2-fench1 propylidene propanedinitrile and 1.9 g of 3, 3-dimethoxy-1 subjected to chromatography. -methyl-2 Fensch-Propylidene-25 propanedinitr1-sha, which is obtained in accordance with examples 18 and 19, in 100 ml of THF. As a result of carrying out the procedure described in Example 20 and recrystallization from ethanol 30, 2.4 g of the desired mixture with m.p. 157-163 ° C.
    Example 22. A mixture of 2-amino-4-methyl-5-phenyl-3-pyridinecarboxylic 35 acid with 2-amino-6-metsh-5-phenyl-3-pyridinecarboxylic acid.
    2 g of the mixture of example 21 with 2 g of potassium hydroxide in 90 ml of ethylene glycol is incubated for 2 hours at 150-40. Then an additional 3 g of potassium hydroxide is added to the mixture, and the mixture is heated under reflux for an additional 2 hours. Next, the reaction mixture is poured into 45 water and neutralized to a pH of 4-5, resulting in a gain of 5.5 g of crude solid product in the form of various fractions with so pl. 258-272 ° С (with decomp.). This raw product is again SO
    9 g of potassium hydroxide is saponified in 90 ml of ethylene glycol at 170 ° C for 12 h. Then this reaction mixture is poured into water and neutralized to pH 7. At the same time, 55
    a brownish solid that is filtered off, and NMR spectral analysis confirms that
    is the desired product (4.45 g with a melting point of 264-270 ° C (with decomp.).
    Example 23 A mixture of 4-methyl-5-phenyl-2-pyridylamine with 6-metip-5-phenyl-2-pyridylamine and its separation.
    9.8 g of the mixture of example 22 and 2 g of powdered copper in 100 ml of quinoline are kept in an oil bath at 255-290 ° C (mostly at 260270 ° C) for about 3-4 hours until the reaction is complete. Thin-layer chromatographic analysis (alumina-ethyl acetate / 10% methanol) shows the presence of two possible amine spots A and B. The reaction mixture is subjected to chromatographic treatment with 600 ml of neutral alumina grade BejbbM. Elution with ethyl acetate makes it possible to first isolate quinoline, then spot A along with some impurities, then spot B. Elution of spot B is completed with a mixture of ethyl acetate with 5-10% methanol. The spot B material is recrystallized from a mixture of toluene and petroleum ether to give tan crystals, which, according to NMR spectroscopic analysis, are the target 4-methyl product with mp. 109-113 ° C (yield 2.35 g).
    The spot A material is also recrystallized from a mixture of toluene and petroleum ether, as a result of which brownish needle-like crystals are obtained, which, as shown by NMR spectral analysis, are the target 6-methyl product with mp. 112-116 ° C (yield 1.1 g).
    Calculated, I: C 78.23; H 6.57-, N 15.21.
    Found,% C 78.03; H 6.37j N 15.01.
    Example 24. 1- (2,6-Dichlorobenzoyl) -3- (6-methyl-5-phenyl-2-pyrvdil) -urea.
    620 mg of 2,6-dichlorobenzoyl isocyanate are mixed with 500 mg of 6-methyl-5-fenl-2-pyridipamine in 25 ml of ethyl acetate at room temperature. As a result, a precipitate is formed, which is filtered and, using NMR spectrum, it is established that it is The target product is ductr. 219-220 C, product yield 460 mg, 42.2%, Calculated,%: C 60.02; H 3.78-, N 10.50. Found,%: C 59.77; H 3.66; N 10.42. Example .25. 1- (2,6-Dichlorobenzoyl) -3- (4-methyl-5-phenyl-2-pyridyl) -urea. 1.4 g of 2,6-dichlorobenzoyl isocyanate is reacted with 0.9 g of 4-methyl-5-phenyl-2-pyridylamine in dichloroethane. Immediately after combining the reagents, an exothermic reaction begins, which is accompanied by self-boiling with a reverse chiller. Then the reaction mixture was stirred at room temperature, no HQ precipitate was formed. After distillation from the mixture of volatile fractions, the residue is recrystallized from ethanol, resulting in 1.0 g of a tan crystal with mp. 210-214 C. The identity of the product obtained to the target was confirmed by NMR spectral analysis and a product yield of 51.1%. Calculated,%: C 60.02; H 3.78; N 10.50. Found,%: C 60.22; H 3.69 .N 10.21. Example 26. 3-Phenylpentan-2, 4-dione. To a solution of 4.46 g of phenipacetone, 0.6 g of p-toluenesulfonic acid and acetic anhydride in a water bath at room temperature with stirring and 34.8 g of 36% boron trifluoride acetic acid are added dropwise. After stirring overnight, solid precipitate, which is collected and washed with water, and then subjected to boiling with reflux in 100 ml of water and 9.0 g of sodium acetate for 2-3 g. The initial reaction mixture is also kept at a higher temperature together with 200 ml of water and 13.5 g sodium acetate for the same of time. Both mixtures are separately extracted, followed by washing with saturated sodium bicarbonate solution until acid is removed. The ethereal fractions are dried and then evaporated in vacuo with the resulting oil-like residue, which solidifies (yield 1.4 g, mp, 40-52c). : Example 27. 3-It1ano-4,6-dmethyl-5-phenyl-2-pyridoi. 24.6 g of 3-fenpentang-2, 4-dione are dissolved in approximately 50 ml. diethyl ether, and then the prepared solution is added to a solution of 7.8 g of sodium methoxide in 200 ml of diethY. ETHERAL ether. A precipitate formed immediately, which was dissolved with stirring after adding 100 ml of water. The aqueous solution of sodium salt of 3-phenylpentane-2,4-dione thus prepared is treated with 2-cyanoacetamide, 2 ml of acetic acid, 4.9 ml of water and piperidine, the amount of which is sufficient to give the solution a basic reaction. Thereafter, the reaction mixture is refluxed overnight, resulting in an oil-like residue. To bring the H value of the solution to 5, acetic acid is added to it, and after cooling, the water is decanted and ethanol is added to ensure the collection of a solid product, the yield of which is 7.05 g, and so on. 355-368 C (with decomp.) Calculated,%: C 74.98; H5.39; N 12.49. Found,%: C 72.18; H 4.97; N 11.82. Example 28: 2-Chloro-4,6-dimethyl-5-phenyl-3-pyridinecarbonitrile. 7.0 g of 3-cyano-4,6-dimesh1-5-phenyl-2-pyridone and 12.1 g of phenylphosphonium dichloride are incubated for 2-3 hours at 175-180 ° C. Then the solution is cooled, poured into a mixture of ice-water and alkalinized by adding ammonium hydroxide. As a result, a precipitate is formed, which is collected, dried in air and subjected to NM-spectral analysis confirming that it is the target product (yield - 7.6 g, mp. 118-123 ° C). Example 29. 2-AMINO-4,6-dimetttt-5-phenyl-3-pyridine baseline. 8.3 g of 2-chloro-4,6-dimethyl-5-phenyl-3-pyridinecarbonitrile are dissolved in 110 ml of DMSO and treated with ammonia gas at 100-110 ° G. After approximately 66 hours of exposure at elevated temperature and treatment with ammonia, the reaction mixture is cooled and poured into a mixture of water and ice. The resulting solid precipitate is collected, washed with water, and then dried in a drying oven. The identity of the product obtained is verified by NMR spectral analysis “Example 30. 2-Amino-A, 6-dimethyl-5-phenyl-3-pyridinecarboxylic acid, 0.5 g of 2-amino-4,6-dimethyl-5- phenyl-3-pyridinecarbonitrile and 1.0 g of potassium hydroxide are kept in 15 m of ethylene glycol at a temperature of approximately 165 ° C for about 6 hours. Then the reaction mixture is drunk in a mixture of water and ice, followed by acidification to pH 4-6 As a result, a solid is formed which is collected, washed with water and identified by thin-layer chromatography and NMR ectral anal as The target product, EXAMPLE 31, 4,6-D1methyl-5-fnyl-2-pyridylamine, 6.1 g 2-amino-4,6-dimethyl-5-pheny-3 -pyridinecarboxylic acid and 1.0 powdered copper are incubated for about 3 hours in 50 ml of quinoline at 270-290 ° C. Next, the entire reaction mixture is chromatographed on 600 ml of Grace 923 grade silica gel using first diethyl ether and then ethyl acetate. , resulting in a gain of 3.0 g of the target product with t, pl, 105-112 ° C. Calculated,%: C 78.75; H 7.12; N 14.13, Found,%: C 78.59, H 6.97; N13.93, PRI me R 32, 1- (2-Xporbenzoyl) -3- (4,6-dimethyl-5-phenyl-2-pyridyl) -urea, 0.5 g of 4,6-dimethyl- 5-phenyl-2-pyrimyl amine is dissolved in 25 ml of acetonitrile and the reaction between the solution (in a stream of nitrogen at room temperature) and 0.6 g of 2-chlorobenzyl isocyanate is carried out. A precipitate immediately formed, and the reaction mixture was stirred for approximately 2 hours during those readings. The resulting solid product was collected, washed with a small amount of acetonitripe and identified by the NMR spectral analysis as a target product with a mp. 176-189 ° C, product yield 300 mg, t, e. 77%. Calculated,%: C, 66.40; H 4.78; N 11.06, Found,%: C 66.68; H 4.63; N 11.20, Example 33, gamma-Acetylbenzene butainitrile, 0.6 g of sodium is added to 120 g of phenylacetone and the mixture is stirred at 95 ° C until the sodium melts. Excess heat is removed and the products react for another 5 minutes, resulting in complete sodium dissolves. Next, 31.8 g of acrylonitrile is added dropwise with a period of 20-25 minutes while cooling to maintain the temperature. The reaction mixture is then stirred for an additional 30 minutes, cooled with ice-water and neutralized with 4 ml of glacial acetic acid. After adding diethyl ether, the mixture is washed 5 times with water, dried over sodium sulfate, and evaporated in vacuo. As a result, the oil is yellow oil, which is distilled. At 115 ° C and a residual addition of 0.50 mm hp, st, the liquid began to be successively distilled, with several fractions being collected. The target compound identified by NMR spectral analysis, with traces of impurities, is collected at boiling point 120122 ° C. Calculated,%: C 76.98; H 7.00; N 7.48, Found,%: C 75.76; H 6.89; N 6.83, Example 34. 3,4-Dihydro-6metsh1-5-phenyl-2 / 1H / -pyridone. At 0-5 C, 1.5 g of ethanol is added to a solution of 4.92 g. Gamma-acetyl-benzene-butonnitrile in 150 ml of diethyl, skip simultaneously. a weak stream of gaseous hydrogen chloride is passed through the solution, the reaction mixture is held under dry conditions and after about 3 hours of barbration with hydrogen chloride, it is left to stand for about 18 hours. Then the solvent is removed from it in a vacuum, resulting in oil-like - the ny product which partially hardens. After addition of approximately 5 ml of ethanol, a water-insoluble precipitate is formed, which is collected and disintegrated into half a powder in acetone of 0.32 g of product with m.p. 310330 ° C. Calculated,%: C, 76.98; H N 7.48. Found,%: C 76.75; H 6.78; N 7.40. PRI me R 35. 6-Methyl-5-phenyl -2 / 1H / -pyridone. 25.6 g of 3,4-dihydro-6-methyl-5-phenip-2 / 1H / -pyridone and 4.9 g of 5% palladium on coal are refluxed with reflux for about 18 hours. 750 ml of p-cumene. Since, after cooling, little product is formed, the reaction mixture is boiled and nejje is driven to a constant temperature of 173 ° C. Boiling continues for 36 hours, then the reaction mixture is filtered while hot. After cooling, a solid precipitate forms, which is collected and washed with diethyl ether, resulting in a yield of 13.0 g of product with mp. 201208 ° C. Example 36. 6-Metsh1-5-phenip -2-pyridylamine. A mixture of 12.0 g of 6-methyl-5-phenyl-2-pyridone and 14.4 g of phenyl phosphorus was kept in 300 ml of diphenyl ether for 19-20 hours at a temperature of approximately 220,225 ° C (250 ° C). After cooling, the reaction mixture is chromatographed on silica gel using ethyl acetate. In total, 0.8 g of the target product is collected, which is pre-recrystallized from a mixture of dichloromethane and petroleum e-4mr (mp. 110-113 C). Calculated,%: C 78.23; H 6.57; N 15.21. Found,%: C 78.46, H 6.29, N 15.07. . Example 37. gamma-Acetyl-BM-methylbenzolbutanenitrile. 0.2 g of sodium is added to 40 g of fenipacetone, and the mixture is stirred at 95 ° C until the sodium melts. Excess heat of reaction is then removed, and the products are reacted for another 5 minutes to completely dissolve the sodium. Then, at 80 ° C, 13.4 g of crotonitrite are added at 20 ° C for 25-25 minutes while cooling to maintain the temperature. Next, 43, the reaction mixture is kept at 80-85 ° C for approximately 3-4 hours, after which it is cooled and neutralized with a small amount of glacial acetic acid. After diethyl ether was added, the mixture was washed 5 times with water, dried over sodium sulfate and evaporated in vacuo. The result is a yellow oil, which is distilled in vacuo. The target product is distilled at 140-142 ° C and a residual pressure of 0.5-0.6 mm Hg, which makes it possible to isolate 20.5 g of the product. Calculated,%: C 77.58; H 7.51, N 6.96. Found,%: C 77.72, H 7.28; N 6.77. Example 38. 4,6-Dimethyl-5-phenyl-2-pyridylamine. The conversion of gamma-acetyl-beta-metbenzenebutanenitrile to the desired product is carried out in accordance with Examples 34-36. Example 29. 1- (2,6-Difluorobenzosch1) -3- (6-methyl-5-phenyl-2-pyRidyl) -urea. 500 mg of 6-methyl-5-phenyl-2-pyridylamine is reacted with 650 mg of 2,6 difluorobenzoyl in 25 ml of ethyl acetate. As a result, a residue is formed, which is filtered off, dried and identified by NMR spectral analysis as a target product with mp. 206-208 C, product yield 600 mg, i.e. 62.5%. Calculated,%: C, 65.39; H 4.12; N 11.14. Found,% C 65.35; H 3.87; N 11.29. Example 40. 1- (2,6-Dichlorobenzoyl) -3- (4,6-dimethyl-5-phenyl-2-pyridyl) -urea. In 25 ml of etipacetate, 500 mg of 4,6-d1-meth-1-5-phen-1-2-pyridylamine is reacted with 650 mg of 2,6-dichlorobenzo-pisocyanate. As a result, a precipitate forms, is filtered off, dried and by NMR-spectral analysis identified as the target product with so pl. 230-235 C, product yield 800 mg, i.e. 76.7%. Calculated,%: C 60.88; H 4.14; N 10.14. Found,%: C 60.63; H 4.03; N 10.13.
    211
    Example 41 4- (4-Chlorophenyl) -2-cyano-5- (dimethylamino) -2,4-pentadienecarboxylic acid, ethyl ester.
    50.5 g of the vinamidine salt of example 10 in 160 ml of pyridine at a temperature below 0 ° C in a bath of a mixture of dry ice and acetone are treated with sodium ethoxide, obtained by dissolving 3.5 g of sodium in 160 ml of ethanol at a temperature below 0 ° C, 16, 9 g of ethyl cyanoacetate is added dropwise to the reaction mixture with its cooling so that the temperature of the reaction mixture is kept below 5 ° C. After that,. the mixture was allowed to warm to room temperature and stirred for about 18 hours. The solvent was then removed in vacuo. chloroform was added and the solution was washed several times with water. During drying, the solvent is removed, and the remaining solid material is recrystallized from ethanol, resulting in a yield of 27.5 g of product with m.p. 168-170s. Thin-layer chromatographic analysis (diethyl ether) gave one yellow spot with traces of material at the beginning. A small sample of the final product (380 mg) is recrystallized again to obtain a product that melts at 168-170 ° C,
    Calculated,%: C 63.05-, H 5.62-, N 9.19.
    Found:% C, 62.83; H 5.38, N9.27.
    Example 42 2. Amino-5- (4-chlorophenip) -3-pyridinecarboxylic acid, 1-oxide ethyl ester.
    3.04 g of 4- (4-chlorofensh1) -2-cyano-5- (dimethylamino) -2,4-pentadienecarboxylic acid ethyl ester and 1.04 g of hydroxylamine HG1 in 20 ml of pyridine are stirred for 18 hours at 20-25 ° WITH. The reaction mixture is then poured into water, as a result of which rapid precipitation occurs. After separation and washing with water, the solid product is recrystallized from zanol to give 2.6 g of substance with m.p. 141-153 C.
    . Calculated,%: C, 57.44; H, 4.48; N 9.57.
    Found,%: C 57.68; H 4.51; N 9.72.
    58043. 22
    Example 43. 6-Chloro-5- (4-chlorophenyl) -2-formamido-3-pyridinecarboxylic acid, ethyl ester.
     g of dry DMF is added dropwise to 114 ml while cooling to maintain the temperature at 40 ° C or below. 23.8 g of 2-amino-50- (4-chlorophenyl) -3-pyridinecarboxylic acid 1-oxide ethyl ester is added in one portion. As a result, the temperature rapidly rises to the boiling point and after 15–25 min. The reaction mixture is cooled, followed by
    5 ROSy removal from it. The residual oil is poured into a mixture of ice-water and dichloroethane is added thereto. Then the organic layer is washed repeatedly with saturated
    Sodium bicarbonate solution, followed by drying and stripping in vacuum of light fractions, resulting in an oil-like product that hardens. Thin-layer chromatography 5 graphical analysis (dichloromethane) shows the presence of a predominantly desired product, although there are some impurities in it. The solid product is noticeably soluble in
    0 dichloromethane. It is subjected to chromatographic treatment on Volem silica gel using dichloromethane (6-7 gallons, 22.712-26.497 l of dichloromethane is necessary), as a result of which 13.4 g of product are obtained, with a pl. 184-187 ° C.
    Example 44: 2-Amino-6-chloro-5- (4-chlorophenyl) -3-pyridinecarboxylic acid, ethyl ester.
    0.5 g of 6-chloro-5- (4-chlorophenyl) -2-formamido-3-pyridinecarboxylic acid (ethyl ester) is partially dissolved in 50 ml of ethanol, and the solution is treated with about 5-6 drops of concentrated hydrochloric acid . The reaction mixture was refluxed for about 3 hours, and after cooling, a solid precipitate was collected, the yield of which was 350 mg, and so pl. | 95-198C.
    Calculated,%: C 54.04; H 3.89; N 9.00.
    Found,%: C 34.26; H 3.80;
    / 9,29.
    Example 45. 2-Amino-6-chloro-. -5- (4-chlorophenyl) -3-pyridinecarboxylic acid. 0.3 g of 2-amino-6-chloro-5- (4-chlorophenyl) -3-pygidinone-boonic acid ethyl ester is partially dissolved in 3 ml of water and 3 ml of dioxane, and then 0.2 g of hydrate is added to the solution sodium oxide. The reaction mixture is refluxed for 1.5-2 hours. After neutralizing the glacial acetic acid mixture, a precipitate is formed, which is collected and washed with water to obtain approximately 250 mg of product with a mp. 280-284 ° C (with decomp.). Calculated,%: C 50.91; H 2.85; N 9.89. Found,%: C 48.86; H 2.60; N 9.38. 46. 6-Chloro-5- (4 Example-chlorophenyl) -2-pyridamide. 9 g of 2-amino-6-chloro-5- (4-chlorophenyl) -3-pyricinecarboxylic acid, 300 ml of sulfuric acid and 90 ml of water are kept in an oil bath at 220-230 0 for 1 hour. Then the reaction mixture is diluted They are cooled down and neutralized with 50% sodium hydroxide. The result is a gummy solid which is only partially removed by filtration. Next, the filtrate is subjected to an extrusion treatment with 800-1000 ml portions of dichloromethane four times, taking precautions against the possible removal of a resinous solid product. The combined dichloromethane layers are dried over magnesium sulfate. The filtered solid is dissolved in etipacetate, and then a mixture of water and solid is extracted with some solvent. Thin-layer chromatographic analysis of this extract shows the presence of the target product and impurities. Then the dichloromethane extracts are filtered. 0.6 g of the target product with the tpl, 178g182S. At the same time, the ethyl acetate extract is treated to obtain a solid residue. Rubbing of this solid product in hot dyspormethane, followed by filtration and stripping of light stocks, yields approximately 0.8 g of the desired product with T.Sh1. 179-183 C. Example 47. 1- (2,6-Difluorobenzoyl) -3- Sat-chloro-5- (4-chlorophenp) -2-pyridyl-urea. 0.3 g of 6-chloro-5- (4-chlorophen1111) -2-pyridylamine is dissolved in 25 ml of acetonitrile and treated with 0.5 g of 2,6-difluorobenzene isocyanate in a stream of nitrogen and at room temperature. A precipitate almost immediately formed, and after approximately 3 hours of stirring, the solid product was collected and washed with acetonitrile, resulting in a yield of 0.36 g of product with m.p. 237-241 With, the product yield of 63.3%. Calculated,%: C 54, H 2.63-, N 9.95. Found.%: C 54.26; H 2.67; N 10.15. Example 48. 6- (4-Chlorophenyl) -3-cyano-2-pyridone. A mixture of 100 g of 4-chloroacetophenone with 48 g of ethyl formate was added dropwise over 3 hours to the intensively stirred cold suspension of sodium methoxide in 540 ml of anhydrous diethyl ether. To prevent the temperature from rising to 3 ° C, the addition is carried out in an ice bath. After the addition is complete, the ice bath is removed and the reaction mixture is stirred for about 18 hours at room temperature. Thereafter, the benzoyl acetaldehyde sodium salt suspension is extracted with 400 ml of water and separated. 54.5 g of cyanoacetamide, a solution of 9 ml of acetic acid, 22 ml of water and a sufficient amount of piperidine are added to the mixture to establish an alkaline reaction, which is determined using litmus paper. The reaction mixture is then refluxed for 2 hours, acidified by the addition of acetic acid to pH and cooled thoroughly. The resulting solid product is then heated twice in ethanol under reflux and the insoluble material is collected each time. NMR spectral analysis showed that this solid insoluble material is the desired product with mp, pl. 33,333 ° C, which is used without further purification. 25 Calculated,%: C 62.49-, F1 3.06; N12.15 / Found: C 63.63j H 3.57j N 12.68. Example 49. 2-Chloro-6- (4-chlorophenyl) -3-pyridinecarbonitrip. 42 g of - (4-chlorophenyl) -3-cyano-2-pyridone and phenylphosphonyl dichloride, incubated for 2.5 hours at 175-180 ° C, taking precautionary measures to maintain dry conditions of the reaction. After cooling, the reaction mixture is poured into 500 ml of an ice-water mixture, after which it is slightly alkalinized by addition of concentrated ammonium hydroxide. As a result, a solid product is formed, which is thoroughly saturated with water and recrystallized from a mixture of ethanol and DMF, about 42 g of product with mp. 179-181 ° Calculated,%: C 57.86; H-2.43; N 11.25. Found,%: C 57.91; H 2.59; N 11.32. Example 50. 6- (4-Chlorfensch-1-3-pyridinecarbonitrile. 2.49 g. 2-chloro-6- (4-chlorophenyl) -3-pyrgvidincarbonitrile is used to conduct —the reaction in the presence of 0.3 g. palladium on carbon in 100 ml of dAF in a Parr agitator The reaction mixture is then filtered and the filtrate is poured into a mixture of ice-water and a solid product is obtained which is collected to recrystallize from ethanol to obtain 0.85 g of substance. Example 51 .. 6- ( 4-Chlorophenyl) -3-pyridinecarboxamide. 1.61 g of 6- (4-chlorophenyl) -3-pyridium carbonitrile, 3.0 ml of 30% hydrogen peroxide, 0.3 ml of 6N sodium hydroxide and about 6 ml of ethanol is placed in a reaction vessel and cooled slightly. The temperature of the reaction mixture is heated to approximately 50 ° C, and the mixture is then stirred for approximately 1 hour. After cooling the reaction mixture, a solid precipitate is formed, which is collected by filtration. chromatographic analysis, the pure product was obtained by heating this solid product in refluxing acetone, resulting in 0.4 g of substance with m.p. 245-258 C. 43.26 Example 52. 6- (4-Chlorophenyl) -3-pyridylamine. 2.14 g of bromine is added dropwise to an ice-cooled solution of 2.68 g of sodium hydroxide in 32 ml of water. Then, in the form of portions, maintaining the temperature at approximately 0 ° C, a paste is added, which contains 6 - (. 4-chlorophenyl) -3-pyridinecarboxyamide and water. After stirring for 30 minutes, the reaction mixture is heated to room temperature, and then it is slowly heated to 75-80 ° C and kept at this temperature for 1 hour. As a result, a dark precipitate is formed, which is filtered off. The solid product thus obtained is dissolved in diethyl ether, and the insoluble matrices are removed by filtration. The ether portion is dried and evaporated in vacuo to give an oil-like residue. This material gives several spots during chromatography on sipicagel using ethyl acetate. Both IR spectral and 5GMR spectral analyzes confirm that the average and most significant spot relates to the target product, whose output is 180-190 mg. Example 53. 1- (2,6-Dichlorobenzoip) (4-xdorfensch) -3-pyridyl-urea 170 mg of 6- (4-chlorophenyl) -3-pyridylamine is dissolved in 45 ml of acetonitrile and treated in a stream of nitrogen and at room temperature 0.25 g of 2,6-dichlorobenzoyl isoate. A precipitate formed almost immediately, and after approximately 2 hours of stirring, this solid product was collected and recrystallized from ethanol to give 20 mg of a substance with a mp. 225-229 ° C. The identity of this product to the target is confirmed by NMR spectral analysis, the yield of the product is 57.1%. Calculated,%: C 54.25-, H 2.88; N 9.99. Found,%: C 54.97; H 3.19; N 10.63., Example 54. 3-Cya1-5-gmethyl-6-phenylpyridone. . This compound is prepared according to Example 48j with the exception that in this case, instead. 4-chloroacetophenone as a starting pearetira and with field; Cozy propylfeion. The final product is made from acetone, in the result of which a substance with m.p. 250-257 C.
    Calculated,%: C 7A, 27; H / 4.79; N 13.33.
    Found,%: C 74.16; H 4.56; N 13.59.
    Example 55. 2-Chloro-5-methyl-6-phenyl-3-pyridinecarbonitrile.
    The target product is obtained in accordance with Example 49. The identity of the target product is confirmed by NMR spectral analysis.
    Example 56. 5-: Methyl-6-Fensch-1-3-pyridinecarbonitrile,
    The target product is obtained in accordance with 50 50. The identity of the target product is determined according to NMR spectral analysis.
    Example 57. 5-Methyl-6-phenyl-3-pyridic carboxamide.
    A target product is obtained in accordance with Example 51. The identity of the target product is determined according to NMR spectral analysis.
    Example 58 58. 5-Methyl-6-phenyl-3-pyridylamine.
    The desired product is obtained in accordance with Example 52. The final product is recrystallized from d-spormethane, and then from petroleum ether to obtain a product with mp. 93-98 ° C.
    Example 59. 1- (2,6-Dichlorobenzoyl) -3- (5-methyl-6-phenyl-3-pyridyl) -urea.
    0.4 g of 5-methylg6-phenyl-3-pyridylamine in 20 ml of acetonitripe in a stream of nitrogen and added at room temperature to 0.5 g of 2,6-dichlorobenzoyl isocyanate. After about 10-20 minutes, a precipitate is formed. The reaction mixture is further stirred for about 4-5 hours, the resulting product is filtered off and washed with acetonitripe, resulting in 580 g of substance with m, mp. 202-205 C. A small amount of this product is recrystallized from ethanol, the product is isolated with m.p. 204-209 С, product code 66,8%.
    Calculated,%: C 60.02; H 3.78-, N 10.50.
    Found,%: C 59.77; H 3.82; N 10.61.
    158043 .28
    Example 60. 6- (4-H. porphrn1) -2-pinridane-1-oxide.
    1.5 g of 5- (4-chlorophenyl) -2-pyridamine, obtained in accordance with. In 5 examples 1-6, in 30 ml of apetone, 1.7 g of 85% 4- (2-metip-4-chlorophenoxy) -butl acid in 30 ml of acetone is added to a solution. After about 5 minutes, a precipitate forms, and after an additional 2 hours, the reaction mixture is cooled in a refrigerator and kept there for about 18 hours. Then this mixture is filtered to obtain 2.1 g of solid material, which is suspended in 200 ml chloroform and mix) together with solid potassium carbonate.
    Next, 4b ml of water is added in order to dissolve 20 the solid product, followed by extraction treatment of the aqueous layer. Thereafter, four additional extraction treatments are carried out using 1-200 ml of 5 chloroform to remove the product. After drying and stirring, a yellowish solid is obtained, which, as shown by NMR spectral analysis, is the target product (yield 1, 2 g), mp. 224-226 ° C.
    Example 61 1- (2,6-Dichlorobenzoyl) -3-C5- (4-chlorophenyl) -2-pyridyl-1-oxyl-urine a.
     0.7 g of 2,6-dichlorobenzo-pisocyanate in dichloromethane is added to a solution of a suspension of 5- (4-chlorophenip) -2-pyridylamine-1-oxide in 25 ml of dichloromethane. A precipitate formed almost immediately. The reaction mixture is stirred for about 3 days. At room temperature, and then after cooling, the precipitate is filtered off, resulting in 5 of 510 mg of the desired compound, m.p. 235-237 C (with decomp.), Product yield 51.5%.
    Calculated,%: C 52.26; H 2.77; N 9.62.
    0 Found,%: C 52.50, H 2.69;
    N 9.67.
    Example 62. 4-Dimeshtamino-3-phenyl-3-buten-2-one.
    A mixture of 13.4 g of phenylacetone with 13.0 g of 5 dimethylformamide dimethyl acetal is kept at 90-95 ° C on a steam bath for approximately 2.5 hours. The result is a crude oil-like product, which is then subjected to a chromatographic image of 600 ml of using ethyl acetate as eluent. The final product, the structure of which is confirmed by the NMR-spectral data of Hoio Anapiz, is 15.5 g of a yellow oil-like material, which crystallizes on standing. Example 63, 3-Cyano-6-methyl-5-phenyl-2-pyridone. A mixture of 14.1 g of 4-dimethylamino-3-phenyl-3-buten-2-one with 5.9 g of cyanoacetate amide in 100 ml of methanol was added to 7.9 g of sodium methoxide in 100 ml of methanol. This mixture is refluxed for 18 hours, the residue is dissolved in a small amount of hot water. Acidification of the solution to a pH of 6-7 allows a gummy solid to be obtained which is collected by filtration. Giving the most acidification to reduce the pH gives only an oil-like product. Rubbing the resin-like product in ethnyl acetate and cooling it produces not combining a white solid product, which is identified as the target product (yield, 2.8 g); 280-290 ° C. PRI me R 64. 2-Amino-6-methyl-5-phenyl-3-pyridinecarbonitrile. The conversion of Z-cyano b-methyl-5-phenyl-2-pyridone, obtained according to example 63, to the target product in accordance with examples 3 and 4 is carried out. The structure of the final product is confirmed by NMR spectral analysis, m.p. is 182-189 ° C. Example 65. 2-Amino-6-methyl-5-phenyl-3-pyridinecarboxylic acid. This product was obtained in accordance with Example 5. The structure of the final product was confirmed by NMR spectral analysis, its T. pl. Is 300-308 ° C (c). Example 66. 6-Methyl-5-fvnil -2 pyridylamine. This product is obtained in accordance with Example 6 (another procedure is described in Example 23). The chemical structure of the final product is confirmed by NMR spectral analysis. 4330 Note 67. 1 - (2-Iip () M6PH3oip) - 3- (6-methyl-tfln and h-2-pyridyl) -urea. Conduct peaKiuw) 650 mg of 2-brs1mbenloylisocyanate with SOOm of 6-methyl-5-fench1-2-g of irSh1Ilami and in 25 ml of ethyl acetate. As a result, a precipitate is formed, which, as determined after filtering, constitutes the desired product, m.p. 172-177 (, product yield 83.4%. Example 68. 4-Chloro-gamma- (1-oxoethyl) -beta-methyl-isobutane nitrip. G of Triton B is added dropwise to 21.8 g of 4-chlorophenylacetone in 78 ml of butanol. After this, 9.17 g of crotononitrile are added to the mixture in the same way with initial cooling to lower the temperature to. Since this reaction is not exothermic, no additional cooling is necessary after the desired temperature is reached. at 65 ° C for 2.5 hours and after cooling on an ice bath to the mixture, 262 ml of 1N hydrochloric acid is added in portions.The reaction mixture is then extracted with diethyl ether, washed with water, dried and evaporated in vacuo. This gives an oil-like product that is distilled into a vacuum. C. to obtain 18.6 g of the substance with a bp 130-131 ° C. Example 69. 4-Chloro-gamma-1- (methoxyimino) -ethyl-beta-methylbenzene butanethyl, 4.4 g 4-chloro-gamma- (1-hydroxyethyl) -beta-methylbenzobutadiene and 3.7 g of methoxyamine hydrochloride in 80 ml of pyridine are stirred at room temperature. This mixture is then poured into ice containing enough concentrated hydrochloric acid to neutralize pyridine, stirred and extracted with dichloromethane. The prepared dichloromethane solution is washed with water and with a high-grade sodium chloride solution, followed by drying over the magnesium sulfate. Filtration and stripping of the lungs. fractions allows to obtain a transparent, colorless, resinous product, which, by no means the NMR and IR spectra of glue analyzes, constitutes a color only up to one ton. Calculation.%, C: 63.51, H 6, 47; N 10.58. Found,%: C 63.80; H 6.19; N10.63. Example 70. 5- (4-Chlorophenyl) -A, 6-dimethyl-2-pyridylamine. 19.5 g of methanesulfonic acid in 500 ml of ductile,
    chlorobenzene is slowly distilled using a short distillation head and a calcium chloride tube until heterogeneity is eliminated and a bp is reached. 130131 ° C. Over the next 10 minutes, 25 g of 4-chloro-gamma-C1- (methoxyimino) -ethyl-beta-methylbenzobutanenitrile in 150 ml of chlorobenzene is added dropwise in a mixture
    slow distillation and mixing using a magnetic stirrer. The reaction mixture is then boiled for approximately 18 hours, followed by cooling, diluting with dichloromethane and washing with 100 ml of sodium hydroxide, water, and finally with a saturated solution of sodium chloride. After drying over magnesium sulphate, the crude material is subjected to chromatographic chromatography on silica gel using 1 liter of dichloromethane with 1 and 2% methanol and 2.5 l of 5% methanol, resulting in a yield of 8.1 pure target product. The identity of the final product to the target is confirmed by NMR-spectral analysis (mp. 148-152 ° C). Example 71. 1- (2,6-Difluorobenzosch1) -3-G5- (4-chlorophenyl) -4,6-dimethyl-2-pyridylZ-urea. 500 mg of 4,6-dimethyl-5- (4-chlorophenip) -2-pyridylamine and 650 mg of 2,6-fluorobenzoyl isocyanate are reacted in 25 ml of dichloromethane. As a result, a precipitate is formed, which is filtered off, dried and identified by NMR spectral analysis as the desired product with mp. 204206 ° C, the product yield of 34.7%. Calculated,%: C 60.66; H 3.88i N 10.11. Found,%: C 60.54j H 3.85; N.9,86. Ana.pogi1 synthesize other typical compounds listed in Table. one.
    forged Egyptian, hiking worms, fall-hiking worms, meadow moths, hawk moths, pennies, beet-hiking worms, mole cabbage, imported cabbage Worm; Orthoptera, in particular the red cockroach, the American cockroach and Thysanoptera, in particular the cyanopods.
    The proposed compounds may
    for the control of other insects, in particular, with a small cow duster, a cattle grub, an autumn flint, a face fly, mosquitoes, a fly fly larva, a tabanid. fly, cutworms aktebiey, small Diptera insects, southwestern kzpsuruznoy borer, corn grinder, horse bot fly, larva 4332 G1red.pagaemg11e compounds may be nspolzovaE {s for controlling various iasekommn Neg rows including otr d Coleoptera, in particular ladybird beetle of the Colorado bird, Khrushchev J Diptera larvae, in particular, yellow-fever mosquito, house fly, Lepidoptera, in particular, corn moth, scoop of cotton flakes, scoop of cotton, used for cabbage spring, scoop of pecanmit casebearer, pink boxworm shovels, hickory moth caterpillar, scoop, green clover pins, alfalfa catepillar, miners , grape leafwraper, sheep ruminze, sheeterworms in general and spruce bud worms. It is likely that the proposed compounds act on the mechanism of transformation of insects, thereby causing their death. The insecticidal activity of the proposed compounds is determined by testing for their effectiveness against a ladybird larva and a southern butterfly worm larva. The compositions are applied to the foliage of the plants, after which this foliage is fed to the larvae. The proposed compounds are tested in a wide range of concentrations that vary from about 1UUO to 1 hour / 1,000,000 hours. Compositions based on each of the tested compounds are prepared by diluting the compound in a solvent prepared using small amounts of Toximul R products and Toximul S, usually respectively 5.9 and 4.0 g / l anhydrous mixture in the ratio of 1 g of 1 ethanol and acetone. Water is then added to the solution in an amount necessary to prepare a solution that contains this compound at a concentration of 1000 ppm. In a further portion of the liquid, it is diluted with water containing small amounts of Toximul-R and Tox1shul S products, which allows prepare solutions for lower concentration treatments. The product Toximul R, as well as the product Toksimul S, is a sulfonate (non-ionic mixture manufactured by Stepan Chemical Company). A solution of the test compound is sprayed in two (101.6 mm) square pots with bean plants, and in each of the pots has from 6 to 10 plants. Then the plants are allowed to dry, 12 leaves are removed from them, and the cut ends are wrapped with cotton wool moistened with water. Next, the leaves are divided into six plastic cups. Petri sizes of 100 f 20 mm. Five larvae of a second-age ladybird at the second age and five larvae of the southern butterfly are placed in each of three Petri dishes. After this, the cups are placed in thermoNumber of surviving larvae in - number of surviving larvae Percentage efficiency Number of surviving larvae in
    A comparison of the biological activity of the proposed and known compounds shows a higher in the first case, the percentage of insect extermination (for diflyubensuron, the percentage of destruction of the southern butterfly worm is lower). one
    The comparison results are shown in Table. 2
    The effectiveness of the fight against a ladybird and a moth worm at various concentrations of the proposed compounds is given in Table. 3 and 3 in which the temperature and relative humidity are maintained at approximately approximately 25.6 ° C and 51%, respectively, for 4 days, and after this time, the first evaluation of the effectiveness of the tested compounds is made. After this assessment, two fresh sheets are placed in each cup plants previously treated in pots. Petri dishes are again kept in a room with adjustable temperature and relative humidity for an additional three days, after which they are finalized for seven days. The insecticidal effect is about limit by counting the number of surviving larvae on each plate.The results of all treatments are compared with the results achieved with solvent treatment and in the absence of treatment.The following rating scale is used: 0-0% 1-1-50% 2 51- 99% 3-100% control efficacy. The test results are summarized in Table 1. The proposed compounds are tested under similar conditions, but at lower concentrations. During these tests, the effectiveness of insect control is determined by counting the number of survivors. for each Petri dish using the Abbot formula: control experiment after processing the control-experiment
    35
    72 1- (2-Chlorobenzoyl) -3- (5-phenyl-2-pyridyl) -urea
    72 1- (2-Chloro-6-fluorobenzosht) -3-G5 - (- chloro-phenyl) -2-pyridyl-urea
    741- (2-Methylbenzoyl) (4-chlorophenyl-2-pyridyl-urea
    751- (2-Chloro-6-methoxybenzoyl) (4-chlorophenyl) -2-pyridate-urea
    761- (2,6-Dichlorobenzoyl) (3-chlorophenyl) -2-pyridyl-urea
    771- (2,6-Dichlorobenzoyl) (4-bromophenip) 2-pyrcdyl} urea
    78t1 (2-chlorobenzoyl) -3-C5- (4-bromophenyl) -2-pyridyl} urea
    791- (2,6-Dinetoxybenzoyl) -3-5-4-bromophenyl) -2-pyridyl urea
    801- (2,6-Dichlorobenzoyl) -3-C5- (4-yl) -2-pyrcyl-urea
    811- (2,6-Dimethoxybenzoyl) -3-C5- (4-tolyl) -2 pyrvdsh13-urea
    821- (2,6-Dichlorobenzoyl) -3-G5- (3-trifluoromethylphenyl) -2-pyridyl2-urea
    831- (2-Chlorobenzoyl) -3-G5- (3-trifluoromethylphenyl) -2-pyridylJ-urea
    841- (2,6-Dnmetoksibenzonl) 3- (trifluoromethyl) -fencyl -2-pyridine-urea
    851- (2,6-Difluorobenzosh1) C3- (tr fluoromvtil) -phenyl -2-pyridyl | -urea
    861- (2,6-Dichlorobenzoip) -3-G5- (4-methoxyphenyl) -2-pyridine-urea
    871- (2,6-Dichlorobenzoyl) (2,4-dichlorophene) -2-pyridyl - ochevina
    36
    P58043 Table 1
    77.3 (205-207) 83.1 ((211-2-21) 56.1 (233-235) 89.5 (212-221) 54.7 (211-216) 58.1 (231-234 )
    67.7 (228-230) 37.3 (221-228)
    65.8 (230-234) 39.7 (197-199) 52.7 (192-194) 71.0 (207-209)
    A4.5 (198-206)
    73.3 (225-227) 52.0 (233-237) 54.5 (214-224)
    37
    1- (2-Chloro-6-fluorobenzoyl) -4-C5- (4-chlorophenyl) -4-methyl-2-pyrvdil-urea
    1- (2-Chlorobenzoyl) -3-C5- (4-bromophenyl) -4-methyl-2-pyridyl-urea
    1 - (2,6-Difluorobenzoyl) -3- B- (A-bromophenyl) -4-methyl-2-pyridyl urea
    1- (2,6-Dichlorobenzoyl) -3-G4-methyl-5- (4-tolsh1) -2-pyridin1} -urea
    1- (2-Chlorobenzoyl) -3-C4-methyl-5- (4-tolyl) -2-pyridine ureas
    1- (2,6-Difluorobenzosch1) -3-C4-methyl-5- (4-tolyl) -2-pyridyl urea
    1- (2-Chlorobenzoyl) -3- З- (3-chlorophenyl) -4-methyl-2-pyridyl urea
    1- (2,6-Difluorobenzoyl) -3-G5- (3-: -chlorophenyl) -4-metsh1-2.-pyrcyl-urea
    1- (2-Chlorbenzoyl) -3- (6-metip-5-feti .n-2-pyr id or urea)
    P580ДЗ38
    Duration tabl, 1
    36.7 (209-215)
    14.2 (210-216)
    20.6 (245-248) 51.7. (208-211)
    47.5 (180-185) 55.2 (208-211)
    34.2 (206-211)
    13.7 (191-204)
    86.6 (213-216)
    1- (2,6-Dimethoxybenzoyl) -3- (6-methyl-5-phenyl-2-pyridsh1) -urea
    1- (2-Methylbenzoyl) -3- (6-methyl-5-phenyl-2-pyridyl) -urea
    1 (2,6-Dichlorobenzoyl) (4-chlorofensh1) -6-methyl-2-pyridine-urea
    "I
    1- (2-Chlorobenzosh1) -3-C5- (4-chlorophenyl) -6-methyl-2-pyridyl-urea
    1- (2,6-Dimethoxybenzoip) -3-C5- (4 chlorophenyl) -6-methyl-2-pyrndyl urea
    1- (2,6-Difluorobenzoyl) (4-chlorenip) -6-me. Methyl-2-pyridine-urea
    1- (2-Fluoro-6-chlorobenzoyl) -3-15- (4-chlorophenip) -6-mvtil-2 pyridine-urea
    1 (2-Chloro-6-methoxybenzoyl) (4-chlorophenyl) -6-methyl-2-pyridyl-urea
    1- (2-Methylbenzoyl) (4-chlorophenyl) -6-met1sh-2-pyridyl-urea
    1- (2,6-Dichlorobenzoyl) -3-C5- (4-methoxyphenyl) -6-methyl-2-pyrvidipurea
    1- (2-Chlorobenzoyl) -3-G5- (4-methoxyphenyl) -6-methyl-2-pyridip 1-urea
    1- (2,6-Dimethoxybenzoyl) -3-G5- (4-methoxyphenip) -6-methyl-2-pyrcyl2-urea
    1- (2,6-Difluorobenzoip) -3-C5- (4-methoxyphenyl) -6-methyl-2-1gar1adsh1-urea
    1- (2-Methylbenzoyl) -3-G5- (4-methoxyenyl) -6-methyl-2-pyridip2-urea
    1- (2,6-Dimethylbenzoyl) -3-G5- (4-methoxyphenyl.) - 6-methyl-2-pinrid1t3-urea
    Continued table. one
    43.5. (188-197) 76.3 (221-222)
    67.1 (225-228)
    67.7 (223-225)
    69.6 (219-222)
    70.8 (218-221)
    76.0 (226-231)
    7J, 2 (225-230) - (231-236)
    74.8 (216-220)
    84.5 (239-241)
    53.51 (203-206)

    87.6 (236-240)
    82.1 (225-229)
    95.7 (218-221) - 1158043 iiizziiiizii 1- (2,6-Dichlorobenzosh1) -3-Sb-methyl 5- (4-tolyl) -2-pyridip} urea 1211- (2-Chlorobenzoyl) -3- b- methyl 5- (4-tolip) -2-pyridyl-urea 1221- (2,6-dimethoxybenzoyl) -3-b-methyl-5- (4-tolsh1) -2-pyrid11l-urea 1231- (2,6 -Difluorobenzoyl) -3-6-methyl-5- (4-tolsh1) -2-pyridsh1 Urea 1241- (2,6-Dimethylbenzoyl) -3 Sb-methyl-5- (4-tolyl) -2-pyridip - urea 1251- (2-Chlorobenzoyl) (4-bromophenip) -6-methyl-2-pyridyl-urea 1261- (2,6-Difluorobenzoyl-3-Sb-netil-5- (3-chlorophenyl) -2-pyridin1 | -urea 1271- (2-chlorobenzoyl) -3- b-chloro-5- (4-chlorophenyl) -2-pyridip} -urea 1281- (2,6-difluorobenzoyl) -3-sat-chloro-5- (4 -chlorophenyl) -2-pyridip - ocheina 1291- (2-Chl6r-6-fluorobenzoyl) -3-Sat-chloro-5- (4-chlorofensch1) -2 pyridyl-3-urea 1301- (2,6-Difluorobenzoyl) -3- (4,6-dimethyl- 5-phenyl-2-pyridyl) urea 1311- (2-Methylbenzokl) -3- (4,6-dimethyl-5-phenyl-2-pyridium t-urea 1321- (2-Chloro-6-fluorobenzoyl) -3 -C5- (4-chlorophenyl) -4,6-dimethyl-2-pyridyl-urea 1331- (2-chlorobenzoyl) -3-G5- (4-chlorophenyl) -4,6-dimethyl-2-pyridyl2-urea 1341 - (2,6-Dichloro-benzoyl) -3- (6-phenyl-3-pyrvdt) -urea 1351- (2-Chlorobenzos1) -3- (6-phenyl-3-pyridyl) -urea 1361- {2,6- Dimethoxybenzoic) -3-6-phenyl-3-pyridyl) -urea 1371- (2-Chlorobenzoyl) -3-G &-( 1-chlorophenip) -3-pyridsh: -urea - 42 table. 1 3 66.7 (203-204) 82.1 (221-223) 33.3 (203-207) 81.4 (223-226) 46.4 (213-216) 8.0 (228-233) 13.6 (194-197) 87.8 (240-243) 76.4 (237-241) 39.9 (215-221) 78.1 (215-218) 84.8 (216-222) 91, 5 (222-225) 89.7 (209-213) 22.0 (209-216) 75.0 (184-194) 54.1 (210-213) 84.8 (214-219)
    43
    2. 1381- (2,6-Dimethoxybenzoyl) -3-Sat- (4-chlorophenyl) -3-pyridyl} -urea
    1391- (2,6-Difluorobenzoip) -3-Sat- (4-chlorophenyl) 3-pyridip urea a
    1401- (2,6-Dichlorobenzoyl) -3-Sat- (3-chlorophenyl) -3-pyridyl} -urea
    1411- (2,6-Dimethoxybenzoyl) (3-chlorphenip) -3-pyrchdip} urea
    1421- (2,6-Dichlorobenzoyl) -3-6- | 3- (tri-fluorimetip) -phenyl-pyridyl} -urea
    1431- (2-Chlorobenzoyl) -3-i6-C3- (trifluorometip) -fensh13-3-pyrvdil-urea
    144 1- (2,6-Dimethoxybenzoyl) -3- (6-E3- (trifluoromethyl) -phenyl-3-pyridsh -: -urea
    1451- (2,6-Dichlorobenzoyl) (4-tolip-3-pyridip} urea
    1461- (2-Chlorobenzoyl) (4-tolyl) -3-pyridyl} -urea
    1471- (2,6-D1 1-methoxybenzoyl) -3-Sat- (4-tolyl) -3-pyridine-urea
    1481 - (2,6-Dichlorobenzosh1) -3- Sat- (4-mexyphenip) -3-pyridyl-urea
    1491- (2-Chlorbenzoyl) -E-Sat- (4-metaxyphenyl) -3-pyrvd1-urea
    1501- (2,6-Dimethoxybenzoyl) -3-Sat- (4-methoxyfennl) -3-pyridine urea
    1511- (2-Chlorbenzosh1) -3- (5-methyl-6-phen-nip-3-pyridkp) urea
      . -.
    1521- (2 6-Dimethoxybenzoyl) -3- (5-methyl-6-phen-3-pyridyl) -ureas
    1531- (2,6-Difluorobenzoip) -3- (5-methyl-6-phenyl-3-pyrvdil) -urea
    1541- (2,6-Dichlorobenzosh1) -3-Сб - (- chlorophenyl) -5-methyl-3-pyriyl-urea
    1551- (27 Chlorobenzoip) -3- Sat- (4-chlorofensh1) -5-metshg-3-pyridyl7gurea
    1158043
    44 Continued table. one
    -1-f76 .4 (214-219)
    92.3 (246-252)
    83.6 (217-220)
    45.7 (19Y94) 52.6 (201-208)
    85.5 (196-199)
    42.9 (185-188)
    78.4 (220-223) 95.9 (206-210)
    56.6 (224-227) 40.1 (203-205) 87.4 (210-213) 43.4 (203-206) 60.7, (160-161) 34.0 (200-205) 82.9 ; (204-208)
    50.4 (178-191)
    43.7 (165-188) A 511580/43 i ::::::: iz ::::::: i 1 1561- (2,6-Dnmethoxybenzoyl) -3-Pb- (4 chlorphenip) -5-methyl -3-pyridyl-urea 1571- (2,6-Difluorobenzoyl) -3-C5- (4-bromophenyl) -A, 6-d # 1 methyl-2-pyridipZ-urea 1581- (2-Chloro-6-fluorobenzoyl) -3-C5- (A-bromophenyl) -4,6-dimethyl-2-pyr1Idyl-mrchevin, 1591- (2-Chlorobenzoyl) (4-bromophenyl) -4,6-dimetip-2-pyridyl-urea 1601- ( 2,6-Dichlorobenzoyl) (- 4-bromophenyl) -4,6-dimethyl-2-pyridip-mo. Chevine 1611- (2,6-Difluorobenzoyl) -3-C4,6-dimethyl-5- (4-methoxyphenyl) -2-pyridyl-urea. 1621- (2-Chloro-6-fluorobenzoSh1) -3-C4,6-dimethyl-5- (4-methoxyphenyl) -2-pyridyl-urea 1631- (2-Bromobenzosch1) -3-C5- (4-chlorophenyl) - 2-pyridyl-urea. 1641- (2-Chloro-6-ftrrbenzosh1) -3- (6-methyl-5-fensh1-2-pyridyl) -urea 1651- (2-Bromobenzoyl) -3-b-methyl-5- (4-tolyl) -pyridyl-urea 1661- (2-Bromobenzoyl) -3-G5- (4-chlorophenyl) -4,6-dimethyl-2-pyridate1-Urea 1671- (2-Chloro-6-methoxybenzoyl) -3-C5- ( 4-chlorophenyl) -4,6-dimethyl-2-pyridyut D-urea 1681- (2-Methylbenzoyl) -3-C5- (4-chlorophenyl) -4,6-dimethyl-2-pyridyl-urea 1691- (2, 6-Dichlorobenzoyl) -3-C5- (4-chlorophenyl) -4,6-dimethyl-2-pyridine-urea. 1701- (2,6-Dimethylbenzoyl) (4-chlorophenyl) -4,6-dimethyl 2-pyrndyl 1-urea 1711- (2,6-Dimethoxybenzoyl) -3-Г5- (4-bromophenip) -4.6- dimethyl-2-pyridyl-urea / ift 1 7.7 (173-177) А8.0 (210-212) 51.1 (227-232) 100 (216-224) 36.6 (207-220) 75.9 (224-226) 52.9 (200-207) 85.4 (223-230) 48.1 (194-198) 79.1 (208-214) 47.4 (210-213) 73.5 (235-240) 84.0 (218 -224) 84.7 (232-234) 72.3 (248-251) 7.6 (250-256 ;.
    table 2
    Table 3
    Continued table. 3
    51
    .
    1000
    100 1000
    100 1000
    100 1000
    100 1000
    100 1000
    100 1000
    100
    1000
    100 1000
    100 1000
    100 1000
    100 1000
    100
    52
    P58043 Continued table. 3
    3 2 3 3 3 3 3 3 3 3 2
    one
    3 3
    3 2 2 1 3 2 3 3 3 3
    53
    1000
    eight
    100
    9 1000
    100 1000
    0
    100
    91 1000
    100 1000
    2
    100 1000
    93
    100 1000
    94
    100 1000
    95
    100 1000
    96
    100 1000
    97
    100 1000
    98
    100 1000
    99
    100
    115804.Ч
    5 Continuation of the table. 3
    3
    Continued table. 3
    57
    11580DAY
    58 Continued table. 3
    59
    60
    158043 Continued table. 3
    Table 3 continuation
    Continued table. 3 Efficiency Concentration in the processing of H / 1 mln. Ladybug
    After 4 days 1 After 7 days
    100 1000
    ioo
    100 1000
    100 1000
    100 1000
    100 1000
    100 1000
    Ioo
    100 Test result not determined due to a valid bo connection. The result was not determined.
    E
    After 4 days I After 7 days
    3 3 3 3
    .3. 3 3 3 3 3 3 3
    3 3 2 Continuation of the table.3 of insect control Worm moth absent c. The solution is active. Table 4
    67
    1 158043-68
    Continued table. BUT
    g
    2.5 1 10
    5 2.5
    one
    100 50 25 10 10
    five
    2.5
    1 10
    five
    2.5
    1,100
    50 25 10 100 50 25 10
    Continued table. BUT
    77
    100 50 25 10 10
    20
    five
    2.5
    t, o
    100
    13
    50 25 10 10
    five
    2.5
    1.0
    1.0
    0.5
    0.25
    0.125
    100
    50
    25
    ten
    1158043
    78 Continued table. four
    100
    100
    100
    100
    79
    ten
    5.0
    2.5
    1.0 100 50 25 10 10
    5.0
    2.5
    one
    0.5
    0.25
    0.125
    0.063
    100
    50
    25
    ten
    100
    50
    25
    ten
    i 80
    1158043
    Continued table. four
    ABOUT
    81
     10 5
    2.5
    about 1.0 100 10 5 1
    100
    50
    ten
    one
    100 50 25 10
    100 10
    five
    1.0 50 25 10
    1.0
    82
    l Continuation of the table. 4 |
    83
    100 50 25 10 10 5
    67
    2.5 1.0 1.0 0.5 0.25 0.125 100 50 10 1.0
    33 0.5 0.25 0.125 100
    50 25
    ten
    ten
    five
    84
    1158043 Continuation of the table. four
    100
    27
    100
    100
    2.5 1.0 1.0 0.5 0.25 0.125 1.0 0.5 0.25 0.125 100
    10 1.0 0.5 1.0 0.5 0.25 0.125 100
    50
    25
    10,100
    50
    Continued table. four
    87
    88
    1158043 Continuation of the table. And
    89
    25
    10,100
    50
    25
    ten
    100
    50
    25
    ten
    100
    50
    25
    ten
    100
    50
    25
    ten
    ten
    five
    2.5
    one
    100 50
    90
    1 I 58043 Continued table. 4 Efficiency of fight against Concentration when processing, Ch. / 1 million h. Ladybird Insect Worm Butterfly
    3:
    After 4 days I After 7 days
    . ten
    1 10
    1 10
    1 10
    1 10
    1 Result undetermined due to no connection. The result is not determined.
    3 3 3 3 3 2 3
     3 2 active solution
    权利要求:
    Claims (4)
    [1]
    METHOD FOR PRODUCING 1-BENZOIP-3- (ARILPYRIDYL) UREA DERIVATIVES of the general formula where each of R is an atom of hydrogen, bromine, chlorine or fluorine a, or methoxy, provided that both radicals do not simultaneously mean a hydrogen atom, and also provided when one of the radicals R is a fluorine or methoxy atom, the other radical R cannot be water
    η is an integer from 0 up to 1; R <- independently ozna- atom of chlorine or methyl; m is an integer from 1 up to 2; Rj phenyl radical
    general formula ^ 3 (0-
    [2]
    2)
    J ^ 4 (0-2) where R % is the atom of bromine, chlorine, fluorine or CF,;
    R * is methyl or methoxy, provided that the phenyl radical contains no more than two different substituents, and the substituents on the pyridine ring are in the following positions:
    a) the NH group with respect to the pyridine nucleus is in the second position of the ring, the group R ^ is in the fifth position of the pyridine ring, and if w χ. 1-2, any substituent is in the fourth, sixth or fourth and sixth positions of the pyridine ring, except when R 4 is a chlorine atom, is in the sixth position of the nucleus and m <- 1 · if m and η = 0 and each R is methoxy, Rj is unsubstituted phenyl,
    [3]
    3-chlorphenip, 3,4-dichlorophenyl or
    [4]
    4-methoxyphenyl;
    if m and η = 0 and each of R is methyl, Rt is not 4-chlorophenyl;
    by birth;
    if m th η = 0, and one of R is a chlorine atom and the other is a hydrogen atom, R a is not 3-chlorophenyl, 3,4-dichlorophenyl, 4-tolyl, 4-methoxyphenyl;
    if w = 2 and η = 0, one of R is a chlorine atom and the other R is a hydrogen atom, Rj is not 3-chlorophenyl, 3,4-dichlorophenyl, 4-tolyl or 4-methoxyphenyl;
    if m = 2 and η = 0, one of Ri is methyl, the other is R, not a chlorine atom;
    if η = 1, none of R is-; is methyl or methoxy, any of R is methyl or a chlorine atom, R t is a chlorine atom, Rt is phenyl, in the para position substituted by a bromine, chlorine or fluorine atom, methyl or CF,;
    if η = 1 and one of R is a hydrogen atom, w = 1-2;
    or
    b) the group ΝΗ relative to the pyridine ring is in the third position of the nucleus, the group R2. is in the sixth position of the pyridine ring, and if w - 1, any of the substituents R "is in the fifth position of the pyridine ring, with the exception of compounds in which w = 0-1, if η = 0, R <is methyl, if η = 0 , one of R is methyl, and the other is a hydrogen atom, R ^ is not unsubstituted phenyl,
    if η = 1, each from R - atom chlorine or fluorine, R ^ - methyl, a Rj - para-substituted phenyl atom bromine chlorine or fluorine, methyl, different I'm the one what
    benzoyl derivative of the general formula
    CNCO II t
    where R has the indicated meanings, is reacted with a pyridine derivative of the general formula
    I o * where Rf, Rx, spike have the indicated meanings, and the target product is isolated in free form.
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    同族专利:
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    引用文献:
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    NL160809C|1970-05-15|1979-12-17|Duphar Int Res|METHOD FOR PREPARING BENZOYLURUM COMPOUNDS, AND METHOD FOR PREPARING INSECTICIDE PREPARATIONS BASED ON BENZOYLURUM COMPOUNDS.|
    US4219557A|1978-08-31|1980-08-26|Eli Lilly And Company|1--3-urea compounds and insecticidal use|
    GR71911B|1978-08-31|1983-08-16|Lilly Co Eli|JPH0223287B2|1981-02-03|1990-05-23|Inoue Japax Res|
    IL70169D0|1982-11-18|1984-02-29|Sterling Drug Inc|2-pyridinones,their preparation and pharmaceutical compositions containing them|
    US4617316A|1984-03-14|1986-10-14|Fmc Corporation|Insecticidal heteroaryl substituted phenyl benzoylureas|
    DK88186A|1985-03-01|1986-09-02|Duphar Int Res|BENZOYLURINE INGREDIENTS WITH ANTITUMOR ACTIVITY|
    US4684477A|1985-03-06|1987-08-04|Chisso Corporation|Pyridine derivatives and their use in liquid crystals|
    AT77817T|1985-04-30|1992-07-15|Dresden Arzneimittel|3-CYAN-PYRIDINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR PHARMACEUTICAL USE.|
    DE4223013A1|1992-07-13|1994-01-20|Bayer Ag|Process for the preparation of 2,5-disubstituted pyridines|
    DE4234637A1|1992-10-14|1994-04-21|Bayer Ag|Process for the preparation of 2-substituted 5-alkyl-pyridines|
    DE4301109A1|1993-01-18|1994-07-21|Bayer Ag|Process for the preparation of 6-amino-nicotinonitriles|
    DE4301110A1|1993-01-18|1994-07-21|Bayer Ag|Process for the preparation of 2-amino-5-aminomethyl-pyridine|
    JP2002322152A|2001-04-24|2002-11-08|Koei Chem Co Ltd|Production method of cyanopyridines|
    US9260394B2|2011-01-19|2016-02-16|University Of Maryland, Baltimore|Derivatives of nicotinic acid N-oxide, their preparation and their use as inhibitors of enzyme 3-hydroxyanthranilate-3, 4-dioxygenase|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US24033181A| true| 1981-03-03|1981-03-03|
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