Anthranylamide derivative, composition for pest controlling composition for invertebrate insect controlling, method for pest controlling, and intermediates

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to anthranylamide derivative selected from compound of formula I or N-oxides thereof, wherein R1 represents methyl, F, Cl, Br; R2 represents F, Cl, Br, I, CF3; R3 represents CF3, Cl, Br, OCH2CF3; R4a represents C1-C4-alkyl; R4b represents H, CH3; and R5 represents Cl, Br, and agriculturally acceptable salt thereof. Also disclosed are composition for pest controlling containing biologically effective amount of formula I and at least one additional component selected from group comprising surfactants, solid and liquid diluents; composition for invertebrate insect controlling containing biologically effective amount of formula I and at least one additional biologically active compound or agent. Also disclosed are method for insect controlling as well as intermediates such as benzoxazinone and parasolocarboxylic acid derivatives.

EFFECT: compounds with insecticide activity, useful in insect controlling.

20 cl, 16 tbl, 33 ex

 

Background of the invention

This invention relates to certain anthranilamide, their N-oxides, agricultural-acceptable salts and compositions and methods of use thereof for combating invertebrate pests such as arthropods (Arthropoda), both in agriculture and non-agricultural conditions.

Combating invertebrate pests such as arthropods, is extremely important to achieve high efficiency of cultivation of agricultural crops. Damage to invertebrate pests of growing and stored crops can cause significant reduction in productivity and thereby lead to increased cost for the consumer. Important is also combating invertebrate pests in forestry, in the cultivation of greenhouse crops, ornamental crops, growing seedlings, stored food and fiber products, and also pests of livestock, household and public health and animal health. Many products are commercially available for these purposes, but remains a need for new compounds that are more effective, less costly, less toxic, safer for the environment or with different mechanisms of action

In NL 9202078 described derivatives of N-acylanthranilic acid of the formula i as insecticide.

where

X denotes a direct bond;

Y denotes N or C1-C6alkyl;

Z represents NH2, NH(C1-C3alkyl) or N(C1-C3alkyl)2; and

R1-R9independently denote H, halogen, C1-C6alkyl, phenyl, hydroxy, C1-C6alkoxy or1-C7acyloxy.

The invention

This invention relates to the compound of formula 1, its N-oxide or an agricultural acceptable salt of this compound

where

R1denotes CH3, F, Cl or Br;

R2denotes F, Cl, Br, I or CF3;

R3means CF3, Cl, Br or OCH2CF3;

R4astands With1-C4alkyl;

R4bdenotes N or CH3and

R5denotes Cl or Br.

This invention relates to compositions for combating invertebrate pests, containing a biologically effective amount of the compounds of formula 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. This invention relates also to compositions, tereasa biologically effective amount of the compounds of formula 1 and an effective amount of at least one additional biologically active ingredient or agent.

This invention relates also to a method of combating invertebrate pests, providing contacts bespozvonochnykh pest or its environment with a biologically effective amount of the compounds of formula 1 (e.g., as described herein compositions). This invention relates to such a method in which bespozvonochnykh pest or its environment is brought into contact with a biologically effective amount of the compounds of formula 1 or a composition containing the compound of formula 1 and a biologically effective amount of at least one additional compound or agent for the destruction of invertebrate pests.

This invention relates also to the connection of benzoxazinone formula 2

where

R1denotes CH3, F, Cl or Br;

R2denotes F, Cl, Br, I or CF3;

R3means CF3, Cl, Br or OCH2CF3;

R5denotes Cl or Br;

which is applicable as an intermediate product in the synthesis to obtain the compounds of formula 1.

This invention relates also to the connection pyrazolylborate acid of formula 4

where

R3means CF3, Cl, Br or OCH2CF3; and

R5denotes Cl or r;

which is applicable as an intermediate product in the synthesis to obtain the compounds of formula 1.

Detailed description of the invention

In the above listing, the term "alkyl", used alone or in compound words such as "alkylthio" or "halogenated"means having a straight chain or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl or the different butyl isomers. The person skilled in the art it will be clear that not all nitrogen-containing heterocycles can form N-oxides as nitrogen must be available lone pair of electrons for oxidation to the oxide; the person skilled in the art will understand, any nitrogen-containing heterocycles can form N-oxides. The person skilled in the art will also understand that tertiary amines can form N-oxides. Synthetic methods to obtain the N-oxides of heterocycles and tertiary amines are very well known to the person skilled in the art including the oxidation of heterocycles and tertiary amines with peroxynitrate, such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkylhydroperoxides, such as tert-butylhydroperoxide, perborate sodium and dioxirane, such as dimethyldioxirane. These methods obtain the N-oxides have been described in detail and discussed in the literature, see, nab the emer: T.L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S.V. Ley, Ed., Pergamon Press; M. Tišler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A.J. Boulton and A. McKillop, Eds., Pergamon Press; M.R. Grimmett and B.R.T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A.R. Katritzky, Ed., Academic Press; M. Tišler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A.R. Katritzky and A.J. Boulton, Eds., Academic Press; and G.W.H. Cheeseman and E.S.G. Werstiuk in Advances in Heterocyclic Cheniistly, vol. 22, pp 390-392, A.R. Katritzky and A.J. Boulton, Eds., Academic Press.

The compounds of this invention can exist as one or more stereoisomers. Different stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. The person skilled in the art will understand that one of streamer can be more active and/or may be the best action to take when the enrichment of the mixture relative to the other stereoisomer (other stereoisomers) or when separated from the other stereoisomer (other stereoisomers). In addition, the person skilled in the art knows how to separate, enrich, and/or to selectively receive said stereoisomers. Thus, the invention includes compounds selected from compounds of formula 1, their N-oxides and agricultural acceptable salts. The compounds of this invention can be in the form of a mixture of stereoisomers, in the form of an individual stereoisomer or optically active form.

Salts of the compounds of this is subramania include acid additive salt (salt absorption) with inorganic or organic acids, such as Hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluensulfonate or valeric acid.

Preferred compounds of cost, ease of synthesis and/or biological effectiveness are:

The preferred connection 1: connection of formula 1, where R4Astands With1-C4alkyl, and R4bdenotes H; or R4Adenotes CH3and R4bdenotes CH3.

The preferred connection 2: preferred connection 1, where R5denotes Cl.

The preferred connection 3: preferred connection 2, where R4bdenotes CH3CH2CH3CH(CH3)2or(CH3)3.

The preferred connection 4: preferred compound 3, where R2denotes Cl or Br.

The preferred connection 5: preferred compounds 4, where R1denotes CH3.

The preferred connection 6: the preferred compounds 4, where R1denotes Cl.

The preferred compound 7: compound of formula 1, where R1denotes CH3, Cl or Br; R2denotes F, Cl, Br, I or CF3; R3denotes CH3, Cl or Br; R4Astands With1With 4alkyl; R4bdenotes N and R5denotes Cl or Br.

Especially preferred is the compound of formula 1 selected from the group consisting of:

the compounds of formula 1, where R1denotes CH3, R2denotes Br, R3means CF3, R4Adenotes CH(CH3)2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Br, R3means CF3, R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Br, R3denotes Br, R4Adenotes CH(CH3)2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Br, R3denotes Br, R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Br, R3denotes Cl, R4Adenotes CH(CH3)2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Br, R3denotes Cl, R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

is soedineniya formula 1, where R1denotes CH3, R2denotes Cl, R3denotes CH3,R4Adenotes CH(CH3)2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3denotes CH3,R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3denotes Br,R4Adenotes CH(CH3)2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3denotes Br,R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3denotes Cl,R4Adenotes CH(CH3)2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3denotes Cl,R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3means OCH2CF3, R4Adenotes CH(CH3) 2, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3means OCH2CF3, R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes Cl, R2denotes Cl, R3denotes Br,R4Adenotes CH3, R4bdenotes N and R5denotes Cl;

the compounds of formula 1, where R1denotes CH3, R2denotes Cl, R3means OCH2CF3, R4Adenotes CH3, R4bdenotes N and R5denotes Cl.

Preferred compositions of this invention are compositions which contain the above preferred connection. Preferred methods of application are methods of using the above preferred compounds.

Preferred are compounds of formulas 1, 2 and 4, in which R1denotes CH3, Cl or Br; R2denotes F, Cl, Br, I or CH3; R3denotes CH3, Cl or Br; R4Astands With1-C4alkyl; R4bdenotes N and R5denotes Cl or Br.

The compounds of formula 1 can be obtained using one or more of the following methods and options, while the data in schemes 1-11. Define R1, R2, R3, R4A, R4band R5in the compounds of formula 1-24 below are the same as those defined above under summary of the invention, unless otherwise indicated.

The compounds of formula 1 can be obtained by the reaction of benzoxazinones formula 2 with C1-C4bonds alkylamines, as shown in General scheme 1.

Scheme 1

This reaction can be run neat or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, dichloromethane or chloroform with optimum temperatures ranging from room temperature to the temperature of reflux distilled (boiling under reflux solvent. The overall reaction benzoxazinones with amines to obtain anthranilamide well described in the chemical literature. In relation to a review, see Jakobsen et al., Bioorganic and Medicinal Chemistry 2000, 8, 2095-2103 and cited in this review link. Cm. also G.M. Coppola, J. Heterocyclic Chemistry 1999, 36, 563-588.

Benzoxazinone formula 2 can be obtained in various ways. Two methods that are particularly applicable, described in schemes 2-3. In scheme 2 benzoxazine formula 2 is obtained directly binding pyrazolylborate acid of formula 4 with an Anthranilic acid of formula 3.

Scheme 2

It involves the sequential addition of methanesulfonanilide in the presence of a tertiary amine such as triethylamine or pyridine, to pyrazolylborate acid of formula 4 with the subsequent addition of Anthranilic acid of formula 3, followed by a second addition of tertiary amine and methanesulfonanilide. This method usually gives good output benzoxazinone and illustrated in more detail in example 1.

Scheme 3 shows an alternative getting benzoxazinones formula 2 using linking the carboxylic acid of formula 6 with an anhydride Stanovoy acid of formula 5 to obtain directly benzoxazinone formula 2.

Scheme 3

This reaction is applicable solvent, such as pyridine or a mixture of pyridine/acetonitrile. The anhydrides of the acids of formula 6 can be obtained from the corresponding acids of formula 4 by known methods, such as chlorination with thionyl chloride or oxalylamino.

Anthranilic acid of formula 3 can be obtained by known methods. Many of these compounds are known. As shown in figure 4, Anthranilic acid, containing as substituent R2chlorine, bromine or iodine, can be obtained by direct halogenoalkanes unsubstituted Anthranilic acid of formula 7 N-chlors what czinkota (NCS), N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS), respectively, in solvents such as N,N-dimethylformamide (DMF), to obtain the corresponding substituted acid of the formula 3.

Scheme 4

Getting anhydrides Stanovoy acid of formula 5 can be made of satinov formula 9, as shown in General scheme 5.

Scheme 5

Satiny formula 9 can be obtained from the aniline derivatives of the formula 8 as described in the literature methods, such as F.D. Popp, Adv. Heterocycl. Chem. 1975, 18, 1-58 and J.F.M. Da Silva et al., Journal of the Brazilian Society 2001, 12(3), 273-324. Oxidation of isatin 9 hydrogen peroxide will usually produce good outputs corresponding anhydride Stanovoy acid 5 (G. Reissenweber and D. Mangold, Angew. Chem. Int. ed. Engl. 1980, 19, 222-223). anhydrides Stanovoy acids may also be derived from Anthranilic acid 3 through numerous well-known methods, including the reaction of 3 with phosgene or an equivalent of phosgene.

Pyrazolylborate acid of formula 4 can be obtained by the method presented in General form in figure 6.

Scheme 6

The reaction of pyrazole with 10 2,3-dehalogenation formula 11 gives a good outputs 1-pildiportaal 12 with good specificity against the desired regioniii. Metallation of 12 diisopropylamide lithium (LD) with the subsequent damping of the lithium salt with carbon dioxide gives pyrazolylborate acid of formula 4. Additional details of the procedures for this method are shown in examples 1, 3 and 5.

Source pyrazoles 10, where R3represents CH3, Cl or Br, are known compounds. The pyrazole 10, in which R3is CH3is commercially available. Pyrazoles 10, in which R3is Cl or Br, can be obtained in accordance with known literature methods (H. Reimlinger and A. Van Overstraeten, Chem. Ber. 1966, 99(10), 3350-7). Apply the alternative method of obtaining 10 in which R3represents Cl or Br, is depicted in scheme 7.

Scheme 7

Metallation of sulfamoylbenzoyl 13 n-butyllithium with subsequent direct halogenoalkanes this anion or hexachlorethane (if R3is Cl)or 1,2-dibromotetrachloroethane (if R3is Br) gives halogenated derivatives 14. Remove sulfamoyl group triperoxonane acid (TFU) at room temperature proceeds smoothly and in good yield with the formation of pyrazoles 10, where R3represents Cl or Br, respectively. Additional experimental details for this method are described in examples 3 and 5.

As an alternative method, illustrated in scheme 6, pyrazolylborate acid of formula 4 where R3means CF3can also be the floor is the modern way presented in a General form in scheme 8.

Scheme 8

The reaction of compounds of formula 15 wherein R6stands With1-C4alkyl, with a suitable base in a suitable organic solvent gives collisionally product formula 16 after neutralization of the acid, such as acetic acid. A suitable base may be, for example, but without limitation, sodium hydride, tert-piperonyl sodium, damsel sodium (dimethyl sulfoxide sodium) (CH3S(O)CH2-Na+), carbonates or hydroxides of alkali metals (such as lithium, sodium or potassium), fluorides or hydroxides of tetraalkyl(for example, methyl, ethyl or butyl)ammonium or 2-tert-butylamino-2-diethylamino-1,3-dimethylpyridine-1,3,2-datafactory. Suitable organic solvent may be, for example, but without limitation, acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethyl sulfoxide or N,N-dimethylformamide. The cyclization reaction is usually conducted in the temperature range from approximately 0 to 120°C. the Influence of solvent, base, temperature and adding time are interdependent, and the choice of reaction conditions is important to minimize the formation of side products. The preferred base is tetrabutylammonium.

The dehydration of compounds of formula 16 with poluchenierazreshenija formula 17 with subsequent transformation of the functional groups of ether carboxylic acid functional group of a carboxylic acid gives compound of formula 4. The dehydration is carried out a processing of a catalytic amount of a suitable acid. This catalytic acid may be, for example, but without limitation, sulfuric acid. The reaction is usually carried out using an organic solvent. As should be clear to the person skilled in the art, the dehydration reaction may be conducted in a wide variety of solvents at temperatures typically between about 0 and 200°C, more preferably between approximately 0 and 100°C. For dehydration in the method of scheme 8 are preferred solvent containing acetic acid, and a temperature of about 65°C. Compounds of esters of carboxylic acids can be converted into compounds of carboxylic acids in many ways, including the nucleophilic cleavage with anhydrous conditions or hydrolytic methods, including the use of either acid, reason (see T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nded., John Wiley & Sons, Inc., New York, 1991, pp. 224-269 in the review of methods). For the method of scheme 8 preferred are base catalyzed hydrolytic methods. Suitable bases include hydroxides of alkali metals (such as lithium, sodium or potassium). For example, the ester can be dissolved in a mixture of water and alcohol, such as ethanol. After processing and sodium hydroxide or potassium hydroxide aired its shades with the formation of sodium or potassium salt of carboxylic acid. Acidification with a strong acid, such as hydrochloric acid or sulfuric acid, yields the carboxylic acid of formula 4. This carboxylic acid can be isolated by methods known to experts in this field, including crystallization, extraction and distillation.

The compounds of formula 15 can be obtained by the method presented in General form in scheme 9.

Scheme 9

where R3means CF3and R6stands With1-C4alkyl.

Treatment of the hydrazine compounds of formula 18 a ketone of formula 19 in a solvent such as water, methanol or acetic acid, gives the hydrazone of formula 20. The specialist in this area should be clear that this reaction may require catalysis selected acid and may also require elevated temperatures depending on the nature of the molecular substitution of the hydrazone of formula 20. The reaction of the hydrazone of formula 20 with a compound of formula 21 in a suitable organic solvent, such as, for example, but without limitation, dichloromethane or tetrahydrofuran, in the presence of an acid acceptor, such as triethylamine, gives the compound of formula 15. This reaction is usually carried out at a temperature of between approximately 0 and 100°C. Additional experimental details for the method of scheme 9 illustrates the example caedite hydrazine of formula 18 can be obtained by standard methods, such as contacting the corresponding halogenated compound of formula 11 with hydrazine.

As an alternative method, illustrated in scheme 6, pyrazolylborate acid of formula 4 in which R3represents Cl or Br, can be also obtained by the method presented in General form in scheme 10.

Scheme 10

where R6is1-C4alkyl.

Oxidation of compounds of formula 22, optionally in the presence of acid to obtain the compounds of formula 17 with subsequent transformation of the functional groups of ether carboxylic acid group, carboxylic acid provides the compound of formula 4. The oxidizing agent may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, monopersulfate potassium (e.g., Oxone®) or potassium permanganate. For a complete transformation should be used at least one equivalent of the oxidizing agent relative to the compound of formula 22, preferably between approximately one and two equivalents. This oxidation is usually carried out in the presence of a solvent. The solvent may be an ether, such as tetrahydrofuran, p-dioxane and the like, an organic ester, such as ethyl acetate, dimethylcarbonate and the like, or a polar APRO the traditional organic solvent, such as N,N-dimethylformamide, acetonitrile and the like Acids suitable for use on stage oxidation, include inorganic acids such as sulfuric acid, phosphoric acid, etc. and organic acids such as acetic acid, benzoic acid and the like Acid when it is used, should be applied in amounts greater than 0.1 equivalents relative to the compound of formula 22. For a complete transformation can be used one to five equivalents of acid. The preferred oxidizing agent is potassium persulfate, and the oxidation is preferably carried out in the presence of sulfuric acid. The reaction can be carried out by mixing the compounds of formula 22 in the desired solvent and, if you use the acid in the acid. Can then be added to the oxidizer at a suitable speed. The reaction temperature usually varies from a low temperature, such as approximately 0°C to the boiling point of the solvent to obtain acceptable reaction rate for completion of the reaction within, preferably, less than 8 hours. The desired product, compound of formula 17 can be isolated by methods known to experts in this field, including crystallization, extraction and distillation. Methods suitable for the conversion of the ester of formula 17 in the carboxylic acid of formula 4, already described for schemes is 8. Additional experimental details for the method of scheme 10 are illustrated in examples 8 and 9.

The compounds of formula 22 can be obtained from corresponding compounds of formula 23 as shown in scheme 11.

Scheme 11

where R6is1-C4alkyl.

Treatment of compounds of formula 23 halogenation reagent, usually in the presence of the solvent gives the corresponding halogenated compound of formula 22. Halogenation reagents that can be used include oxychloride phosphorus, trihalogen phosphorus, pentachloride phosphorus, thionyl chloride, dialoginterface, dialoginterface, oxalicacid and phosgene. Preferred are oxychloride phosphorus and pentavalent phosphorus. For a complete transformation should be used at least 0.33 equivalent oxychloride phosphorus relative to the compounds of formula 23, preferably between approximately 0,33 and 1.2 equivalent. For a complete transformation should be used at least 0.20 equivalent pentachloride phosphorus relative to the compounds of formula 23, preferably between about 0.20 to 1.0 equivalent. The compounds of formula 23 in which R6stands With1-C4alkyl, are preferred is compulsory for this reaction. Typical solvents for the halogenation include halogenated alkanes such as dichloromethane, chloroform, chlorobutane and the like, aromatic solvents such as benzene, xylene, chlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane, diethyl ether and the like, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide, etc. is Optional, can be added an organic base, such as triethylamine, pyridine, N,N-dimethylaniline or the like is not necessary, can also be added to the catalyst, such as N,N-dimethylformamide. Preferred is a process in which the solvent is acetonitrile, and the base is missing. Usually neither the basis nor the catalyst is not required when the solvent used acetonitrile. The preferred reaction is carried out by mixing the compounds of formula 23 in acetonitrile. Then add halogenation reagent within a convenient time, and then this mixture is maintained at the desired temperature until the reaction is complete. The reaction temperature is usually in the range between 20°and the boiling point of acetonitrile, and the reaction time is usually less than 2 hours. Then the reaction mass is neutralized inorganic base, such as sodium bicarbonate, sodium hydroxide and the like, or an organic base, such as and the Etat sodium. The desired product, compound of formula 22 can be isolated by methods known to experts in this field, including crystallization, extraction and distillation.

Alternatively, the compounds of formula 22 where R3denotes Br or Cl, can be obtained by treating the corresponding compounds of formula 22 where R3denotes different halogen (such as Cl to obtain the formula 22 where R3denotes Br or sulphonate group such as p-toluensulfonate, bansilalpet and methanesulfonate, hydrogen bromide or hydrogen chloride, respectively. Using this method, the Deputy halogen or sulfonate R3in the initial compound of formula 22 is replaced by Br or Cl from hydrogen bromide or hydrogen chloride, respectively. This reaction is carried out in a suitable solvent, such as dibromomethane, dichloromethane or acetonitrile. The reaction can be conducted at about atmospheric pressure or at higher pressure than atmospheric pressure, in an autoclave. When R3in the initial compound of formula 22 is a halogen, such as Cl, the reaction is preferably carried out in such a way that the hydrogen halide generated from the reaction, is removed using a bubbler or other appropriate means. The reaction can be conducted at a temperature of between approximately 0 and 100°, Naib is more preferably at a temperature of about ambient temperature (e.g., at approximately 10-40aboutC) and, more preferably, between approximately 20 and 30°C. Adding as a catalyst of the Lewis acid (such as tribromide aluminum, to obtain the compounds of formula 22 where R3is Br) can contribute to this reaction. The product of formula 22 emit conventional methods known to experts in this field, including extraction, distillation and crystallization. Additional details for this method are illustrated in example 10.

The initial compounds of formula 22 where R3denotes Cl or Br, can be obtained by treating the corresponding compounds of formula 23, as already described. The initial compounds of formula 22 where R3denotes a sulphonate group, can also be obtained from corresponding compounds of formula 23 by standard methods such as treatment with sulphonylchloride (for example, p-toluensulfonate) and a base such as tertiary amine (e.g. triethylamine) in a suitable solvent such as dichloromethane; additional details for this method are illustrated in example 11.

As an alternative method, illustrated in scheme 6, pyrazolylborate acid of formula 4 where R3means OCH2CF3can be also obtained by the method presented in General form in figure 12.

CX is 12 mA

where R6stands With1-C4alkyl, and X denotes a leaving (tsepliaeva) group.

In this way, instead of halogenation, is shown in scheme 11, compound of formula 23 are oxidized to compounds of formula 17A. The reaction conditions for the oxidation already described for the conversion of compounds of formula 22 in the compound of formula 17 in scheme 10.

Then the compound of formula 17A alkylate with the formation of the compounds of formula 17b by contact with an alkylating agent of CH3CH2X (24) in the presence of a base. In the alkylating agent 24 X denotes a leaving group in nucleophilic reactions, such as halogen (such as Br, I), OS(O)2CH3(methanesulfonate), OS(O)2CF3, OS(O)2Ph-p-CH3(p-toluensulfonate) and the like; works well methanesulfonate. This reaction is carried out in the presence of at least one equivalent of base. Suitable bases include inorganic bases such as carbonates and hydroxides of alkali metals (such as lithium, sodium or potassium), and organic bases such as triethylamine, diisopropylethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction is usually conducted in a solvent, which may contain alcohols, such as methanol and ethanol, halogenated alkanes, such as dichloromethane, aromatic solvents, t is such as benzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide and the like, Alcohols and polar aprotic solvents are preferred for use with inorganic bases. Preferred are potassium carbonate as base and acetonitrile as solvent. The reaction is usually carried out at a temperature between about 0 and 150°most often between ambient temperature and 100°C. the Product of formula 17b can be selected by using common methods such as extraction. Then the ether of formula 17b transformed into a carboxylic acid of formula 4 by the methods already described for the conversion of compounds of formula 17 in the compound of formula 4 in scheme 8. Additional details for the method of scheme 12 are illustrated in example 12.

The compounds of formula 23 can be obtained from compounds of formula 18, as shown in General form in figure 13.

Scheme 13

where R6stands With1-C4alkyl.

In this way the connection of the hydrazine of formula 18 in contact with the compound of the formula 25 (fumaric ester or maleate ether or can be used a mixture thereof) in the presence of base and solvent. The basis is usually a salt of the metal alkoxide, such as metacentre, the potassium methoxide, ethoxide sodium, atoxic potassium tert-piperonyl potassium tert-piperonyl lithium, etc. you Should use more than 0.5 equivalent of base with respect to the compounds of formula 18, preferably between 0.9 and 1.3 equivalent. You should use more than 1.0 equivalent of the compound of formula 25, preferably between 1.0 and 1.3 equivalent. Can be used proton polar and polar aprotic organic solvents, such as alcohols, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, dimethylsulfoxide and the like, the Preferred solvents are alcohols, such as methanol and ethanol. Particularly preferably, the alcohol was the same with alcohol, which is diluted with fumaric or malaty ether and alkoxide basis. The reaction is usually carried out by mixing the compounds of formula 18 and the base in the solvent. This mixture can be heated or cooled to the desired temperature, and the compound of formula 25 add for some period of time. Usually the reaction temperature is in the range between 0°and the boiling point of the used solvent. The reaction can be conducted at a pressure higher than atmospheric pressure to increase the boiling point of the solvent. Generally preferred are temperatures between about 30 and 90°C. the Time of addition can be the ü so fast far as it allows the heat transfer. Typical periods are adding between 1 minute and 2 hours. The optimum reaction temperature and time are added vary depending on the specific compounds of formula 18 and formula 25. After the addition, the reaction mixture may be maintained for some time at the reaction temperature. Depending on the reaction temperature to the desired aging time can be from 0 to 2 hours. The normal periods of incubation, equal to 10-60 minutes. Then the reaction mass may be acidified by the addition of organic acids such as acetic acid, etc. or an inorganic acid such as hydrochloric acid, sulfuric acid, etc. depending on the reaction conditions and methods of selecting the group-CO2R6the compound of formula 23 can be either hydrolyzed to CO2N; for example, such hydrolysis may contribute to the presence of water in the reaction mixture. If a carboxylic acid (-CO2N), it can be turned back in-CO2R6where R6stands With1-C4alkyl, using methods of esterification are well known in this field. The desired product, compound of formula 23 can be isolated by methods known to experts in this field, such as crystallization, extraction or distillation

It is clear that some reagents and reaction conditions described above, to obtain compounds of formula 1, may not be compatible with certain functional groups in the intermediate products. In these cases, the inclusion of sequences of reactions introduction/unprotect or functional group interconversions in this synthesis will contribute to obtaining the desired products. The application and the choice of protective groups will be obvious to a person skilled in the field of chemical synthesis (see, for example, by T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nded., John Wiley: New York, 1991). The person skilled in the art should be understood that, in some cases, after the introduction of a specific reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of formula 1. The person skilled in the art will also understand that it may be necessary to perform a combination of stages, illustrated in the above schemes, in a different order than the order implied by the specific sequence of reactions presented to obtain the compounds of formula 1.

The authors of the present invention believe that the person skilled in the art using the preceding description, will be able to use this izaberete the s in its greatest extent. Thus, the following examples should be considered only as illustrative and not as limiting whatever follows this description. Stage the following examples illustrate the methodology for each stage in the overall synthetic transformation, and the source material for each stage may not be acquired in a specific preparative experience, the methodology of which is described in other examples or stages. Are percent by weight (wt.%), except percent for chromatographic mixtures of solvents, or where otherwise indicated. Parts and percentages for chromatographic mixtures of solvents are by volume, unless otherwise indicated.1H-NMR spectra are given in ppm in the direction of weak fields from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "to" means Quartet, "m" means multiplet, "DD" means doublet of doublets, "dt" means doublet of triplets, and "Sirs" means broad singlet.

EXAMPLE 1

Obtaining N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Stage A: Obtaining 2-amino-3-methyl-5-chlorbenzoyl acid

To a solution of 2-amino-3-methylbenzoic acid (Aldrich, 15.0 g, to 99.2 mmol) in N,N-dimethylformamide (50 ml) was added N-chlorosuccinimide (13.3 g, and 99.2 mmol) and the reaction see what camping was heated to 100° C for 30 minutes. Heating was stopped, the reaction mixture was cooled to room temperature and left overnight. Then the reaction mixture was slowly poured into a mixture of ice water (250 ml) to precipitate a white solid. The solid was filtered and washed four times with water and then dissolved in ethyl acetate (900 ml). An ethyl acetate solution was dried over magnesium sulfate, evaporated under reduced pressure and the remaining solid was washed with ether to give the desired intermediate as a white solid (13,9 g).

1H NMR (DMSO-d6) δ 2,11 (s, 3H), 7,22 (s, 1H), 7,55 (s, 1H).

Stage b: 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine

To a mixture of 2,3-dichloropyridine (99,0 g, 0.67 mol) and 3-(trifluoromethyl)pyrazole (83 g, 0.61 mol) in dry N,N-dimethylformamide (300 ml) was added potassium carbonate (166,0 g, 1.2 mol) and then the reaction mixture was heated to 110-125°C for 48 hours. The reaction mixture was cooled to 100°and filtered through diatomaceous earth (Celite filter layer® to remove solids. N,N-dimethylformamide and excess dichloropyridine was removed by distillation at atmospheric pressure. Distillation of the product under reduced pressure (BP. 139-141°S, 7 mm) gave the desired intermediate product in the form of a clear yellow oil (to 113.4 g).

1H NMR (CDCl3) δ to 6.8 (s, 1H), was 7.36 (t, 1H), to 7.93 (d, 1H), 8,15 (s, 1H), 8,45 (d, 1H).

Stage C: Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

To a solution of 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine (i.e. the product of the pyrazole from stage B) (105,0 g, 425 mmol) in dry tetrahydrofuran (700 ml) at -75°C was added via cannula a solution of (-30° (C) diisopropylamide lithium (425 mmol) in dry tetrahydrofuran (300 ml). Dark red solution was stirred for 15 minutes, after which carbon dioxide was barbotirovany through the solution at -63°until the solution became pale yellow and did not stop the heat. The reaction mixture was stirred for an additional 20 minutes and then extinguished with water (20 ml). The solvent was removed under reduced pressure and the reaction mixture was distributed between ether and 0.5 N. the sodium hydroxide solution. Water extracts were washed with ether (3x), filtered through diatomaceous earth (Celite filter layer® to remove any remaining solids and then acidified to approximately pH 4, and pH were formed orange oil. Water the mixture was stirred vigorously and added an additional amount of acid to reduce the pH to 2.5-3. Orange oil froze in granular solid, which was filtered, washed successively with water and 1 N. hydrochloric acid and dried in the Aquum at 50° With obtaining specified in the header of the product in the form of solid substances not quite white (130 g). (Product from another experience by the same method melted at 175-176°).

1H NMR (DMSO-d6) δ to 7.61 (s, 1H), 7,76 (DD, 1H), 8,31 (d, 1H), at 8.60(d, 1H).

Stage D: Obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

To a solution of methanesulfonamide (2.2 ml, 28.3 mmol) in acetonitrile (75 ml) was added dropwise a mixture of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (i.e. the product of the carboxylic acid stage) (7.5 g, of 27.0 mmol) and triethylamine (3.75 ml, of 27.0 mmol) in acetonitrile (75 ml) at 0-5°C. Then the reaction temperature was maintained at 0°for the sequential addition of reagents. After stirring for 20 minutes was added 2-amino-3-methyl-5-chlorobenzoyl acid (i.e. the product from stage A) (5,1 g of 27.0 mmol) and stirring was continued for an additional 5 minutes. Then was added dropwise a solution of triethylamine (7.5 ml, 54,0 mmol) in acetonitrile (15 ml) and the reaction mixture was stirred for 45 minutes followed by the addition of methanesulfonanilide (2.2 ml, 28.3 mmol). Then the reaction mixture was heated to room temperature and was stirred overnight. Then to the precipitate 5.8 g of a yellow solid substance was added approximately 75 ml of water. The stage is niteline amount of 1 g of the product was isolated by extraction of the filtrate with getting only 6.8 g specified in the title compound as a yellow solid.

1H NMR (CDCl3) δ to 1.83 (s, 3H), 7,50 (s, 1H), 7,53 (m, 2H), 7,99 (m, 2H), 8,58 (d, 1H).

Stage E: Obtaining N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it (i.e. the product of benzoxazinone stage D) (5.0 g, 11.3 mmol) in tetrahydrofuran (35 ml) was added dropwise Isopropylamine (2,9 ml, 34,0 mmol) in tetrahydrofuran (10 ml) at room temperature. Then the reaction mixture was heated to dissolve all solids and stirred additionally for five minutes, and at this point in time thin layer chromatography confirmed the completion of reaction. The solvent is tetrahydrofuran evaporated under reduced pressure and the remaining solid was purified by chromatography on silica gel, followed by rubbing with a mixture of ether/hexane and receiving specified in the title compound, compounds of the present invention, in the form of a solid (4.6 g), melting at 195-196°C.

1H NMR (CDCl3) δ to 1.21 (d, 6H), 2,17 (s, 3H), of 4.16 (m, 1H), 5,95 (USD, 1H), 7,1-7,3 (m, 2H), 7,39 (s, 1H), and 7.4 (m, 1H), to 7.84 (d, 1H), and 8.50 (d, 1H), 10,24 (USS, 1H).

EXAMPLE 2

Obtaining N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of 6-chloro-2-[1-(3-the ENT-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it (i.e. product benzoxazinone of example 1, stage (D) (4,50 g, 10,18 mmol) in tetrahydrofuran (THF; 70 ml) was added methylamine (2.0 M solution in THF, 15 ml, 30.0 mmol) dropwise and the reaction mixture was stirred at room temperature for 5 minutes. The solvent is tetrahydrofuran evaporated under reduced pressure and the remaining solid was purified by chromatography on silica gel to obtain 4.09 g specified in the title compound, compounds of the present invention, in the form of a white solid, melting at 185-186°C.

1H NMR (DMSO-d6) δ 2,17 (s, 3H), 2,65 (d, 3H), 7,35 (d, 1H), 7,46 (DD, 1H), 7,65 (DD, 1H), 7,74 (s, 1H), 8,21 (d, 1H), 8,35 (uscv, 1H), total of 8.74 (d, 1H), accounted for 10.39 (s, 1H).

EXAMPLE 3

Obtain 3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

Stage a: 3-chloro-N,N-dimethyl-1H-pyrazole-1-sulfonamida

To a solution of N-dimethylsulphamoyl (188,0 g, 1.07 mol) in dry tetrahydrofuran (1500 ml) at -78°C was added dropwise a solution of 2.5 M n-utility (472 ml, 1.18 mol) in hexane while maintaining the temperature below -65°C. After complete addition, the reaction mixture was maintained at -78°C for an additional 45 minutes, after which was added dropwise a solution of hexachloroethane (279 g, 1.18 mol) in tetrahydrofuran (120 ml). The reaction mixture was maintained at -78°within hours, the Naga is evali to -20° And then extinguished with water (1 l). The reaction mixture was extracted with methylene chloride (CH ml); the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride as eluent and receiving specified in the title compound as a yellow oil (160 g).

1H NMR (CDCl3) δ of 3.07 (d, 6H), 6,33 (s, 1H), to 7.61 (s, 1H).

Stage b: 3-chloropyrazole

To triperoxonane acid (290 ml) was added dropwise 3-chloro-N,N-dimethyl-1H-pyrazole-1-sulfonamide (i.e. the product of chloropyrazole stage (A) (160 g) and the reaction mixture was stirred at room temperature for 1.5 hours and then concentrated under reduced pressure. The residue was placed in hexane, the insoluble solids were filtered off and the hexane was concentrated to obtain the crude product as oil. The crude product was further purified by chromatography on silica gel using a mixture of ether/hexane (40:60) as eluent and receiving specified in the header of the product as a yellow oil (64,44 g).

1H NMR (CDCl3) δ to 6.39 (s, 1H), 7,66 (s, 1H), 9,6 (USS, 1H).

Stage C: 3-chloro-2-(3-chloro-1H-pyrazole-1-yl)pyridine

To a mixture of 2,3-dichloropyridine (92,60 g, 0,629 mol) and 3-chloropyrazole (i.e. the product of stage C) (64,44 g, 0,629 mol) in N,N-dimethyl ramida (400 ml) was added potassium carbonate (147,78 g, 1.06 mol) and then the reaction mixture was heated to 100°C for 36 hours. The reaction mixture was cooled to room temperature and slowly poured into ice-cold water. Saducees solid was filtered and washed with water. The solid filter cake was dissolved in ethyl acetate, dried over magnesium sulfate and concentrated. The crude solid was chromatographically on silica gel using a mixture of 20% ethyl acetate/hexane as eluent and receiving specified in the header of the product as a white solid (39.75).

1H NMR (CDCl3) δ to 6.43 (s, 1H), 7,26 (m, 1H), of 7.90 (d, 1H), of 8.09 (s, 1H), to 8.41 (d, 1H).

Stage D: 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

To a solution of 3-chloro-2-(3-chloro-1H-pyrazole-1-yl)pyridine (i.e. the product of pyrazole stage) (39.75 g, 186 mmol) in dry tetrahydrofuran (400 ml) at -78°C was added dropwise a solution of 2.0 M of diisopropylamide lithium (93 ml, 186 mmol) in tetrahydrofuran. Through the amber solution was barbotirovany carbon dioxide within 14 minutes, after which the solution became pale brownish-yellow. The reaction mixture was podslushivaet 1 N. a solution of sodium hydroxide and was extracted with ether (2 x 500 ml). Aqueous extracts were acidified using 6 N. hydrochloric acid and was extracted with ethyl acetate (3 x 500 ml). An ethyl acetate extracts sushi is whether over magnesium sulfate and concentrated to obtain specified in the connection header in the form of solid substances not quite white (42,96 g). (Product from another experience by the same method melted at 198-199°).

1H NMR (DMSO-d6) δ 6,99 (s, 1H), 7,45 (m, 1H), to 7.93 (d, 1H), 8,51 (d, 1H).

Stage E: Obtain 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

To a solution of methanesulfonamide (of 6.96 g, 61,06 mmol) in acetonitrile (150 ml) was added dropwise a mixture of 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product of the carboxylic acid stage D) (15.0 g, 58,16 mmol) and triethylamine (5,88 g, 58,16 mmol) in acetonitrile (150 ml) at -5°C. Then the reaction mixture was stirred for 30 minutes at 0°C. Then was added 2-amino-3-methyl-5-chlorbenzoyl acid (i.e. the product from example 1, stage A) (10,79 g, 58,16 mmol) and stirring was continued for additional 10 minutes. Then was added dropwise a solution of triethylamine (11,77 g, 116,5 mmol) in acetonitrile while maintaining the temperature below 10°C. the Reaction mixture was stirred for 60 minutes at 0°and then added methanesulfonamide (of 6.96 g, 61,06 mmol). Then the reaction mixture was heated to room temperature and was stirred for additional 2 hours. Then the reaction mixture was concentrated and the crude product was chromatographically on silica gel using methylene chloride as eluent to obtain specified in the title compounds as yellow is th solid (9.1 g).

1H NMR (CDCl3) δ is 1.81 (s, 3H), 7,16 (s, 1H), 7,51 (m, 2H), 7,98 (d, 2H), 8,56 (d, 1H).

Stage F: Obtain 3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it (for example, product benzoxazinone stage E) (6,21 g, 15,21 mmol) in tetrahydrofuran (100 ml) was added Isopropylamine (to 4.23 g, 72,74 mmol) and then the reaction mixture was heated to 60°C, was stirred for 1 hour and then cooled to room temperature. The solvent is tetrahydrofuran evaporated under reduced pressure and ostavsheesa solid was purified by chromatography on silica gel with obtaining specified in the title compound, compounds of the present invention, in the form of a white solid substance (of 5.05 g), melting at 173-175°C.

1H NMR (CDCl3) δ of 1.23 (d, 6H), to 2.18 (s, 3H), is 4.21 (m, 1H), 5,97 (d, 1H), 7,01 (m, 1H) 7,20 (s, 1H), 7,24 (s, 1H), 7,41 (d, 1H), 7,83 (d, 1H), 8,43 (d, 1H), 10,15 (USS, 1H).

EXAMPLE 4

Obtain 3-chloro-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it (i.e. the product of benzoxazinone example 3, stage E) (6,32 g, 15,47 mmol) in tetrahydrofuran (50 ml) was added methylamine (2.0 M solution in THF, 38 ml, 77,38 mmol) and the reaction is ionic and the mixture was heated to 60° C, was stirred for 1 hour and then cooled to room temperature. The solvent is tetrahydrofuran evaporated under reduced pressure and the remaining solid was purified by chromatography on silica gel with obtaining specified in the title compound, compounds of the present invention, in the form of a white solid substance (of 4.57 g), melting at 225-226°C.

1H NMR (CDCl3) δ of 2.15 (s, 3H), of 2.93 (s, 3H), 6,21 (d, 1H), 7,06 (s, 1H), 7,18 (s, 1H), 7,20 (s, 1H), 7,42 (m, 1H), 7,83 (d, 1H), 8,42 (d, 1H), 10,08 (USS, 1H).

EXAMPLE 5

Obtain 3-bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

Stage a: 3-bromo-N,N-dimethyl-1H-pyrazole-1-sulfonamida

To a solution of N-dimethylsulphamoyl (44,0 g, 0,251 mol) in dry tetrahydrofuran (500 ml) at -78°C was added dropwise a solution of n-utility (2.5 M in hexane, 105,5 ml, 0,264 mol) maintaining the temperature below -60°C. Thick solid formed during the addition. After complete addition, the reaction mixture was stirred for an additional 15 minutes, after which was added dropwise a solution of 1,2-dibromotetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150 ml) maintaining the temperature below -70°C. the Reaction mixture was bought by orange color and become transparent; the stirring was continued for additionally the x-15 minutes. Bath -78°was removed and the reaction extinguished with water (600 ml). The reaction mixture was extracted with methylene chloride (4) and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using a mixture of methylene chloride-hexane (50:50) as eluent and receiving specified in the title compound as a clear colorless oil (57,04 g).

1H NMR (CDCl3) δ of 3.07 (d, 6H), 6,44 (m, 1H), 7.62mm (m, 1H).

Stage b: 3-bromopyrazole

To triperoxonane acid (70 ml) was slowly added 3-bromo-N,N-dimethyl-1H-pyrazole-1-sulfonamide (i.e. the product of bromopyrazole stage (A) (57,04 g). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The residue was placed in hexane, the insoluble solids were filtered off and the hexane evaporated to obtain the crude product as oil. The crude product was further purified by chromatography on silica gel using a mixture of ethyl acetate/dichloromethane (10:90) as eluent and getting oil. This oil was placed in dichloromethane, neutralized with an aqueous solution of sodium bicarbonate, extracted with methylene chloride (3x), dried over magnesium sulfate and concentrated to obtain specified in the connection header in the form of logo solids (25,9 g), TPL 61-64°C.

1H NMR (CDCl3) δ 6,37 (d, 1H), to 7.59 (d, 1H), 12,4 (USS, 1H).

Stage C: Obtain 2-(3-bromo-1H-pyrazole-1-yl)-3-chloropyridine

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-bromopyrazole (i.e. the product of stage C) (25.4 g, 176 mmol) in dry N,N-dimethylformamide (88 ml) was added potassium carbonate (48.6 g, 352 mmol) and the reaction mixture was heated to 125°C for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 ml). Formed precipitate. The precipitated solid was stirred for 1.5 hours, filtered and washed with water (2 x 100 ml). Solid filter residue was placed in methylene chloride and washed successively with water, 1 N. hydrochloric acid, saturated aqueous sodium bicarbonate and saline. Then the organic extracts were dried over magnesium sulfate and concentrated to obtain and 39.9 g of pink solid. The crude solid is suspended in hexane and stirred vigorously for 1 hour. The solids were filtered, washed with hexane and dried to obtain specified in the title compound in powder form is not quite white (30,4 g), which had a purity of >94% according to NMR. This material was used without additional purification stage D.

1H NMR (CDCl3) δ of 6.52 (s, 1H), 7,30 (DD, 1H), 7,92 (d, 1H), 805 (s, 1H), 8,43 (d, 1H).

Stage D: 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

To a solution of 2-(3-bromo-1H-pyrazole-1-yl)-3-chloropyridine (i.e. the product of pyrazole stage) (30,4 g, 118 mmol) in dry tetrahydrofuran (250 ml) at -76°C was added dropwise a solution of diisopropylamide lithium (118 mmol) in tetrahydrofuran at such a rate that maintained the temperature below -71°C. the Reaction mixture was stirred for 15 minutes at -76°and then carbon dioxide was barbotirovany through it for 10 minutes that caused heated to -57°C. the Reaction mixture was heated to -20°and the reaction is extinguished by water. The reaction mixture was concentrated and then put into water (1 l) and ether (500 ml) and then added an aqueous solution of sodium hydroxide (1 N. 20 ml). Water extracts were washed with ether and acidified with hydrochloric acid. Saducees solids were filtered, washed with water and dried to obtain specified in the title compound as a tan solid (27.7 g). (Product from another experience by the same method melted at 200-201°).

1H NMR (DMSO-d6) δ to 7.25 (s, 1H), 7,68 (DD, 1H), 8,24 (d, 1H), 8,56 (d, 1H).

Stage E: Obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-it

A technique similar to the technique of example 1, stage E, used for p is euromania 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product pyrazolylborate acid of example 5, stage D) (1.5 g, 4,96 mmol) and 2-amino-3-methyl-5-chlorbenzoyl acid (i.e. the product of example 1, stage A) (0,92 g, 4,96 mmol) specified in the title compound in the form of solids (1,21 g).

1H NMR (CDCl3) δ a 2.01(s, 3H), 7,29 (s, 1H), 7,42 (d, 1H), 7,95 (d, 1H), 8,04 (m, 1H), of 8.25 (s, 1H), compared to 8.26 (d, 1H).

Stage F: Obtain 3-bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-it (i.e. the product of benzoxazinone stage E) (0.20 g, 0.44 mmol) in tetrahydrofuran was added Isopropylamine (0,122 ml of 1.42 mmol) and the reaction mixture was heated to 60°C for 90 minutes and then cooled to room temperature. The solvent is tetrahydrofuran evaporated under reduced pressure and the remaining solid is triturated with ether, filtered and dried to obtain specified in the title compound, compounds of the present invention, in the form of a solid (150 mg), TPL 159-161°C.

1H NMR (CDCl3) δ to 1.22 (d, 6H), are 2.19 (s, 3H), is 4.21 (m, 1H), of 5.99 (m, 1H), 7,05 (m, 1H), 7,22 (m, 2H), 7,39 (m, 1H), 7,82 (d, 1H), to 8.41 (d, 1H).

EXAMPLE 6

Obtain 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

To a solution of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-methyl-4H-3,1-benzoxazin-4-it (i.e. the product of benzoxazinone example 5, stage E) (0.20 g, 0.44 mmol) in tetrahydrofuran was added methylamine (2.0 M solution in THF, 0,514 ml of 1.02 mmol) and the reaction mixture was heated to 60°C for 90 minutes and then cooled to room temperature. The solvent is tetrahydrofuran evaporated under reduced pressure and the remaining substance is triturated with ether, filtered and dried to obtain specified in the title compound, compounds of the present invention, in the form of a solid (40 mg), TPL 162-164°C.

1H NMR (CDCl3) δ to 2.18 (s, 3H), 2.95 and (s, 3H), 6,21 (m, 1H), 7,10 (s, 1H), 7,24 (m, 2H), 7,39 (m, 1H), 7,80 (d, 1H), 8,45 (d, 1H).

The following example 7 illustrates an alternative obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid, which can be used to obtain, for example, N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide and N-[4-chlor-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide using additional stages, illustrated in examples 1 and 2.

EXAMPLE 7

Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Stage A: Receive (2,2,2-Cryptor-1-methylethylidene)hydrazone of 3-chloro-2(1H)-pyridinone

1,1,1-triptorelin (7,80 g, to 69.6 mmol) was added to the hydrazone-chloro-2(1H)pyridinone (alternative called (3-chloropyridin-2-yl)hydrazine) (10 g, to 69.7 mmol) at 20-25°C. After complete addition, the mixture was stirred for approximately 10 minutes. The solvent was removed under reduced pressure and the mixture was distributed between ethyl acetate (100 ml) and saturated aqueous sodium bicarbonate (100 ml). The organic layer was dried and evaporated. Chromatography on silica gel (elution with ethyl acetate) gave the product as a solid substance not quite white (11 g, yield 66%), TPL 64-64,5°With (after crystallization from a mixture of ethyl acetate/hexane).

IR (nujol) ν 1629, 1590, 1518, 1403, 1365, 1309, 1240, 1196, 1158, 1100, 1032, 992, 800 cm-1.

1H NMR (CDCl3) δ a 2.12 (s, 3H), 6,91-6,86 (m, 1H), of 7.64-to 7.61 (m, 1H), 8,33-8,32 (m, 2H).

MS m/z 237 (M+).

Stage: Obtain (3-chloro-2-pyridinyl)(2,2,2-Cryptor-1-methylethylidene)hydrazide of ethylhydrocupreine (alternative called (3-chloro-2-pyridinyl)(2,2,2-Cryptor-1-methylethylidene)of hydrazine ethylhydrocupreine)

The triethylamine (20,81 g, 0,206 mol) was added to (2,2,2-Cryptor-1-methylethylidene)hydrazone of 3-chloro-2(1H)-pyridinone (i.e. the product of stage (A) (32,63 g, 0,137 mol) in dichloromethane (68 ml) at 0°C. To this mixture was added dropwise utilisateur (18.75 g, 0,137 mol) in dichloromethane (69 ml) at 0°C. the Mixture was allowed to warm to 25°C for approximately 2 hours. The mixture was cooled to 0°and added dropwise additional portion of ethylchloroformiate (3.7 g, 27,47 mmol) in dichloromethane (14 ml). After approximately one hour, the mixture was diluted with dichloromethane (about 450 ml) and the mixture was washed with water (2 x 150 ml). The organic layer was dried and evaporated. Chromatography on silica gel (elution with a mixture of 1:1 ethyl acetate-hexane) gave the product as a solid (42,06 g, yield 90%), TPL 73,0-73,5°With (after crystallization from a mixture of ethyl acetate/hexane).

IR (nujol) ν 1751, 1720, 1664, 1572, 1417, 1361, 1330, 1202, 1214, 1184, 1137, 1110, 1004, 1043, 1013, 942, 807, 836 cm-1.

1H NMR (DMSO-d6115° (C) to 1.19 (t, 3H), 1,72 (USS, 3H), 4,25 (kV, 2H), 7,65 (DD, J=8,3, a 4.7 Hz, 1H), to 8.20 (DD, J=7,6, 1.5 Hz, 1H), 8,55 (d, J=3.6 Hz, 1H).

MS m/z 337 (M+).

Stage C: Obtain ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate

(3-chloro-2-pyridinyl)(2,2,2-Cryptor-1-methylethylidene)hydrazide of ethylhydrocupreine (i.e. the product of stage C) (5 g, of 14.8 mmol) in dimethyl sulfoxide (25 ml) was added to hydrate tetrabutylammonium (10 g) in dimethyl sulfoxide (25 ml) for 8 hours. After complete addition, the mixture was poured into acetic acid (3.25 g) in water (25 ml). Then after stirring at 25°during the night the mixture was extracted with toluene (4 x 25 ml) and the combined extracts in toluene was washed with water (50 ml), dried and evaporated to obtain a solid substance. Chromatography on silica gel (elution with a mixture of 1:2 ethyl acetate-GE the Sana'a) gave the product as a solid (2.91 in g, the yield is 50%, containing approximately 5% (2,2,2-Cryptor-1-methylethylidene)hydrazone of 3-chloro-2(1H)-pyridinone), TPL 78-78,5°C (after recrystallization from a mixture of ethyl acetate/hexane).

IR (nujol) ν 3403, 1726, 1618, 1582, 1407, 1320, 1293, 1260, 1217, 1187, 1150, 1122, 1100, 1067, 1013, 873, 829 cm-1.

1H NMR (CDCl3) δ to 1.19 (s, 3H), 3,20 (1/2 ABZ pattern, J=18 Hz, 1H), 3,42 (1/2 ABZ pattern, J=18 Hz, 1H), 4,24 (kV, 2H), 6,94 (DD, J=7,9, and 4.9 Hz, 1H), 7,74 (DD, J= 7,7, 1.5 Hz, 1H), 8,03 (DD, 7=a 4.7, 1.5 Hz, 1H).

MS m/z 319(M+).

Stage D: Obtain ethyl 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate

Sulfuric acid (concentrated, 2 drops) was added to ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-5-hydroxy-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate (i.e. the product of stage (C) (1 g, 2,96 mmol) in acetic acid (10 ml) and the mixture was heated to 65°C for approximately 1 hour. The mixture was allowed to cool to 25°and most of the acetic acid was removed under reduced pressure. The mixture was distributed between saturated aqueous sodium carbonate (100 ml) and ethyl acetate (100 ml). The aqueous layer was additionally extracted with ethyl acetate (100 ml). The combined organic extracts were dried and evaporated to obtain the product as oil (0.66 g, yield 77%).

IR (net) ν 3147, 2986, 1734, 1577, 1547, 1466, 1420, 1367, 1277, 1236, 1135, 1082, 1031, 973, 842, 802 cm-1.

1H NMR (CDCl3) δ of 1.23 (t, 3H), 4,25 (kV, 2H), 7,21 (s, 1H), of 7.48 (DD, J=8,1, the 4.7 Hz, 1H), 7,94 (DD, J=6,6, 2 Hz, 1H), 8,53 (DD, J=4,7, 1.5 Hz, 1H).

MS m/z 319(M+).

Stage E: Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Potassium hydroxide (0.5 g, 85%, 2.28 mmol) in water (1 ml) was added to ethyl 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate (i.e. the product of stage (D) (0.66 g, 2,07 mmol) in ethanol (3 ml). After approximately 30 minutes the solvent was removed under reduced pressure and the mixture was dissolved in water (40 ml). The solution was washed with ethyl acetate (20 ml). The aqueous layer was acidified with concentrated hydrochloric acid and was extracted with ethyl acetate (3 x 20 ml). The combined extracts were dried and evaporated to obtain the product as a solid (0,53 g, yield 93%), TPL 178-179°With (after crystallization from a mixture of hexane-ethyl acetate).

IR (nujol) ν 1711, 1586, 1565, 1550, 1440, 1425, 1292, 1247, 1219, 1170, 1135, 1087, 1059, 1031, 972, 843, 816 cm-1.

1H NMR (DMSO-d6) δ to 7.61 (s, 1H), to 7.77 (m, 1H), 8.30 to (d, 1H), at 8.60 (s, 1H).

The following example 8 illustrates an alternative obtain 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, which can be used to obtain, for example, 3-chloro-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide and 3-chloro-N-[4-chlor-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, with the use of the additional stages, illustrated in examples 3 and 4.

EXAMPLE 8

Obtain 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

Stage A: Obtain ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (alternative called ethyl 1-(3-chloro-2-pyridinyl)-3-pyrazolidine-5-carboxylate)

Chetyrehosnuju flask of 2 l, equipped with a mechanical stirrer, thermometer, addition funnel, condenser for reflux distilled and inlet for nitrogen, download absolute ethanol (250 ml) and ethanol solution ethoxide sodium (21%, 190 ml, 0,504 mol). This mixture was heated under reflux for reflux distilled at approximately 83°C. it was Then treated with hydrazone of 3-chloro-2(1H)-pyridinone (68,0 g, 0,474 mol). The mixture is again heated under reflux for reflux distilled (boiling under reflux for 5 minutes. Then the yellow suspension was treated dropwise with diethylmaleate (88,0 ml, 0,544 mol) over 5 minutes. Speed reflux distilled increased markedly during this addition. At the end add all the source material was dissolved. The obtained orange-red solution was maintained at reflux distilled (boiling under reflux) for 10 minutes. After cooling to 65°the reaction mixture was treated with glacial acetic acid (50,0 ml, 0,873 mol). Formed precipitate. The mixture was diluted with water is (650 ml), what caused the dissolution of the precipitate. The orange solution was cooled in a bath with ice. The product began to precipitate at 28°C. the Suspension is kept at approximately 2°C for 2 hours. The product was isolated by filtration, washed with aqueous ethanol (40%, 3 x 50 ml) and then air-dried on the filter for about 1 hour. Specified in the title compound was obtained in the form of highly crystalline, light orange powder (70,3 g, yield 55%). Did not observe significant impurities as1H-NMR.

1H NMR (DMSO-d6) δ to 1.22 (t, 3H), 2,35 (d, 1H), 2.91 in (DD, 1H), 4,20 (kV, 2H), 4,84 (d, 1H), 7,20 (DD, 1H), 7,92 (d, 1H), 8,27 (d, 1H), 10,18 (s, 1H).

Stage: Obtain ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (alternatively called ethyl 1-(3-chloro-2-pyridinyl)-3-chloro-3-pyrazolin-5-carboxylate)

In chetyrehosnuju flask of 2 l, equipped with a mechanical stirrer, thermometer, condenser for reflux distilled and inlet for nitrogen was loaded acetonitrile (1000 ml), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of stage (A) (91,0 g, 0,377 mol) and phosphorus oxychloride (35,0 ml, the 0.375 mol). After the addition of phosphorus oxychloride and the mixture was samaragreaves from 22 to 25°and the formed precipitate. The light yellow suspension was heated under reflux for reflux distilled at 83°C for 35 minutes, after which the wasp is OK disappeared from sight. The obtained orange solution was kept at reflux distilled within 45 minutes, after which it became black and gray. The capacitor used for reflux distilled, replaced distillation head and 650 ml of solvent was removed by distillation. Second chetyrehosnuju flask of 2 l, equipped with a mechanical stirrer, was loaded with sodium bicarbonate (130 g, 1.55 mol) and water (400 ml). Concentrated the reaction mixture was added to a suspension of sodium bicarbonate in 15 minutes. The obtained two-phase mixture was stirred vigorously for 20 minutes, after which the evolution of gas ceased. This mixture was diluted with dichloromethane (250 ml) and then was stirred for 50 minutes. The mixture was treated with a filtering substance of diatomaceous earth Celite® 545 (11 g) and then filtered to remove a black, tarry substance that inhibited the separation of the phases. Because this filtrate was slowly divided into noticeable different phases, it was diluted with dichloromethane (200 ml) and water (200 ml) and was treated with an additional amount of Celite® 545 (15 g). The mixture was filtered and the filtrate was transferred into a separating funnel. The heavier dark green organic layer was separated. Layered phase (uneven layer) (50 ml) was re-filtered and then added to the organic layer. This organic solution (800 ml) was treated with magnesium sulfate (30 g) and Seeley what ielem (12 g) and the suspension was stirred with a magnetic stirrer for 30 minutes. The suspension was filtered to remove the magnesium sulfate and silica gel, which was dark blue-green. The filter residue was washed with dichloromethane (100 ml). The filtrate was concentrated on a rotary evaporator. The product consisted of a dark amber oil (92.0 g, yield 93%). The only identifiable impurities observed using1H-NMR were 1% of the original material and 0.7% acetonitrile.

1H NMR (DMSO-d6) δ to 1.15 (t, 3H), 3,26 (DD, 1H), to 3.58 (DD, 1H), 4,11 (kV, 2H), 5.25-inch (DD, 1H), 7,00 (DD, 1H), to 7.84 (d, 1H), 8,12 (d, 1H).

Stage C: Obtain ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (alternatively called ethyl 1-(3-chloro-2-pyridinyl)-3-chloropyrazole-5-carboxylate)

Chetyrehosnuju flask of 2 l, equipped with a mechanical stirrer, thermometer, condenser for reflux distilled and inlet for nitrogen was loaded ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (i.e. the product of stage C) (with a purity of 95%, 99,5 g 0,328 mol), acetonitrile (1000 ml) and sulfuric acid (98%, of 35.0 ml, 0,661 mol). This mixture was samaragreaves from 22 to 35°adding sulfuric acid. After stirring for several minutes the mixture was treated with potassium persulfate (140 g, 0,518 mol). The suspension was heated under reflux for reflux distilled at 84°C for 4.5 hours. Received the orange suspension is an eye she was still warm (50-65° C)was filtered to remove the fine white precipitate. The filter residue was washed with acetonitrile (50 ml). The filtrate was concentrated to approximately 500 ml on a rotary evaporator. Second chetyrehosnuju flask of 2 l, equipped with a mechanical stirrer, was loaded with water (1250 ml). The concentrated reaction mass is added to the water for about 5 minutes. The product was isolated by filtration, washed with water acetonitrile (25%, 3 x 125 ml), washed once with water (100 ml) and then dried overnight in vacuum at room temperature. The product consisted of orange crystalline powder (79,3 g, yield 82%). The only identifiable impurities observed using1H-NMR were 1.9% of water and 0.6% of acetonitrile.

1H NMR (DMSO-d6) δ of 1.09 (t, 3H), of 4.16 (q, 2H), 7,31 (s, 1H), 7,71 (DD, 1H), scored 8.38 (d, 1H), 8,59 (d, 1H).

Stage D: 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (alternatively named 1-(3-chloro-2-pyridinyl)-3-chloropyrazole-5-carboxylic acid)

Chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, thermometer and inlet for nitrogen was loaded ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. the product of stage (C) (with a purity of 97.5%, 79,3 g, 0,270 mol), methanol (260 ml), water (140 ml) and pellets of sodium hydroxide (13,0 g, 0,325 mol). After adding the guide is sodium oxide and this mixture was samaragreaves from 22 to 35° With original material began to dissolve. After stirring for 45 minutes at ambient conditions entire source material was dissolved. The obtained dark orange-brown solution was concentrated to approximately 250 ml on a rotary evaporator. Then the concentrated reaction mixture was diluted with water (400 ml). The aqueous solution was extracted with ether (200 ml). Then the aqueous layer was transferred into an Erlenmeyer flask of 1 l with magnetic stirrer. The solution was treated dropwise with concentrated hydrochloric acid (36,0 g, 0,355 mol) for about 10 minutes. The product was isolated by filtration, re-suspended in water (2 x 200 ml), washed on the surface once with water (100 ml) and then air-dried on the filter for 1.5 hours. The product consisted of crystalline light brown powder (58,1 g, yield 83%). The only determinable admixture observed using1H-NMR, was 0.7 percent of the ether.

1H NMR (DMSO-d6) δ then 7.20 (s, 1H), 7,68 (DD, 1H), of 8.25 (d, 1H), 8,56 (d, 1H), 13,95 (USS, 1H).

The following example 9 illustrates an alternative obtain 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid, which can be used to obtain, for example, 3-bromo-N-[4-chloro-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide and 3-bromo-N-[4-x is the PR-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, with the use of additional stages, illustrated in examples 5 and 6.

EXAMPLE 9

Obtain 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

Stage A1: Obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (alternatively called ethyl 1-(3-chloro-2-pyridinyl)-3-bromo-2-pyrazolin-5-carboxylate) using oxybromide phosphorus

Chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, thermometer, condenser for reflux distilled and inlet for nitrogen was loaded with acetonitrile (400 ml), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of example 8, stage (A) (50.0 g, 0.185 mol) and oxybromide phosphorus (34,0 g, 0,119 mol). The orange suspension was heated under reflux for reflux distilled at 83°C for 20 minutes. The obtained turbid orange solution was maintained at reflux distilled within 75 minutes, and at this time formed a dense reddish-brown crystalline residue. Condenser for reflux distilled was replaced with a distillation head and gathered turbid colorless distillate (300 ml). Second chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, was loaded with sodium bicarbonate (45 g, 0.54 mol) and water (200 ml). Concentrated the reaction mixture was added to the suspension in sodium bicarbonate for 5 minutes. Received the second two-phase mixture was vigorously stirred for 5 minutes, after gas evolution ceased. The mixture was diluted with dichloromethane (200 ml) and then was stirred for 75 minutes. The mixture was treated with a filtering substance of diatomaceous earth Celite® 545 (5 g) and then filtered to remove a brown resinous substance. The filtrate was transferred into a separating funnel. Brown organic layer (400 ml) was separated and then treated with magnesium sulfate (15 g) and activated carbon Darco® G60 (2.0 g). The resulting suspension was stirred with a magnetic stirrer for 15 minutes and then filtered to remove the magnesium sulfate and charcoal. The green filtrate was treated with silica gel (3 g) and stirred for several minutes. Dark blue-green silica gel was removed by filtration and the filtrate was concentrated on a rotary evaporator. The product consisted of oil with a light amber color (58,6 g, yield 95%), which crystallized upon standing. The only identifiable by1H-NMR admixture was 0.3% acetonitrile.

1H NMR (DMSO-d6) δ to 1.15 (t, 3H), 3,29 (DD, 1H), 3,60 (DD, 1H), 4,11 (kV, 2H), 5,20 (DD, 1H), 6,99 (DD, 1H), to 7.84 (d, 1H), 8,12 (d, 1H).

Stage 2: Obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate using pentabromide phosphorus

Chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, thermometer, condenser for reflux distilled ishodnym hole for nitrogen, downloaded acetonitrile (330 ml), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of example 8, stage A), (52,0 g, rate of 0.193 mol) and pentabromide phosphorus (41,0 g, 0,0952 mol). The orange suspension was heated under reflux for reflux distilled at 84°C for 20 minutes. Received a brick-red mixture was maintained at reflux distilled within 90 minutes, and at this time formed a dense reddish-brown crystalline residue. Condenser for reflux distilled was replaced with a distillation head and gathered turbid colorless distillate (220 ml). Second chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, was loaded with sodium bicarbonate (40 g, 0.48 mol) and water (200 ml). Concentrated the reaction mixture was added to the suspension in sodium bicarbonate for 5 minutes. The obtained two-phase mixture was vigorously stirred for 10 minutes, after which the evolution of gas ceased. The mixture was diluted with dichloromethane (200 ml) and then was stirred for 10 minutes. The mixture was treated with a filtering substance of diatomaceous earth Celite® 545 (5 g) and then filtered to remove purple resinous substance. The filter residue was washed with dichloromethane (50 ml). The filtrate was transferred into a separating funnel. Purple-red organic layer (400 ml) was separated and then treated with magnesium sulfate 15 g) and activated carbon Darco® G60 (2.2 g). This suspension was stirred with a magnetic stirrer for 40 minutes. The suspension was filtered to remove the magnesium sulfate and charcoal. The filtrate was concentrated on a rotary evaporator. The product consisted of oil dark amber color (61,2 g, yield 95%), which crystallized upon standing. The only identifiable by1H-NMR admixture was 0.7% acetonitrile.

1H NMR (DMSO-d6) δ to 1.15 (t, 3H), 3,29 (DD, 1H), 3,60 (DD, 1H), 4,11 (kV, 2H), 5,20 (DD, 1H), 6,99 (DD, 1H), to 7.84 (d, 1H), 8,12 (d, 1H).

Stage: Obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (alternatively called ethyl 1-(3-chloro-2-pyridinyl)-3-bromopyrazole-5-carboxylate)

Chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, thermometer, condenser for reflux distilled and inlet for nitrogen was loaded ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (i.e. the product of stages A1 and A2) (40,2 g, 0,121 mol), acetonitrile (300 ml) and sulfuric acid (98%, at 13.0 ml, 0,245 mol). The mixture was samaragreaves from 22 to 36°after adding sulfuric acid. After stirring for several minutes the mixture was treated with potassium persulfate (48,0 g, 0,178 mol). The suspension was heated under reflux for reflux distilled at 84°C for 2 hours. The obtained orange suspension while it was still warm (50-65° (C)filters is whether to remove the white precipitate. The filter residue was washed with acetonitrile (2 x 50 ml). The filtrate was concentrated to approximately 200 ml on a rotary evaporator. Second chetyrehosnuju flask of 1 l, equipped with a mechanical stirrer, was loaded with water (400 ml). The concentrated reaction mass is added to the water for about 5 minutes. The product was isolated by filtration, washed successively water acetonitrile (20%, 100 ml) and water (75 ml) and then air-dried on the filter for 1 hour. The product consisted of orange crystalline powder (36,7 g, yield 90%). The only identifiable impurities observed using1H-NMR were 1% of the unknown substance and 0.5% acetonitrile.

1H NMR (DMSO-d6) δ of 1.09 (t, 3H), of 4.16 (q, 2H), 7,35 (s, 1H), 7,72 (DD, 1H), 8,39 (d, 1H), 8,59 (d, 1H).

Stage C: 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (alternatively named 1-(3-chloro-2-pyridinyl)-3-bromopyrazole-5-carboxylic acid)

Chetyrehosnuju flask of 300 ml, equipped with a mechanical stirrer, thermometer and inlet for nitrogen was loaded ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. the product of stage C) (with a purity of 98.5%, 25,0 g, 0,0756 mol), methanol (75 ml), water (50 ml) and pellets of sodium hydroxide (3,30 g, 0,0825 mol). After the addition of sodium hydroxide the mixture was samaragreaves 29 do° With original material began to dissolve. After stirring for 90 minutes at ambient conditions entire source material was dissolved. The obtained dark-orange solution was concentrated to approximately 90 ml on a rotary evaporator. Then the concentrated reaction mixture was diluted with water (160 ml). The aqueous solution was extracted with ether (100 ml). Then the aqueous layer was transferred into an Erlenmeyer flask of 500 ml, equipped with a magnetic stirrer. The solution was treated dropwise with concentrated hydrochloric acid (8,50 g, 0,0839 mol) for about 10 minutes. The product was isolated by filtration, re-suspended in water (2 x 200 ml), washed once on the surface water (25 ml) and then air-dried on the filter for 2 hours. The product consisted of crystalline reddish-brown powder (20,9 g, yield 91%). The only identifiable impurities observed using1H-NMR were 0.8% of an unknown substance and 0.7% of the ether.

1H NMR (DMSO-d6) δ to 7.25 (s, 1H), 13,95 (USS, 1H), 8,56 (d, 1H), of 8.25 (d, 1H), 7,68 (DD, 1H).

The following example 10 illustrates an alternative obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate, which can be used to obtain, for example, ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (i.e. the product of the example 9, stage B).

EXAMPLE 10

Obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate from ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate using hydrogen bromide

The hydrogen bromide was passed through a solution of ethyl 3-chloro-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (i.e. the product of example 8, steps In) (8,45 g of 29.3 mmol) in dibromomethane (85 ml). After 90 minutes the current gas was stopped and the reaction mixture was washed with an aqueous solution of sodium bicarbonate (100 ml). The organic phase was dried and evaporated under reduced pressure to obtain specified in the header of the product as oil (9.7 g, yield 99%), which crystallized upon standing.

1H NMR (CDCl3) δ to 1.19 (t, 3H), 3,24 (1/2 of AB in ABX pattern, J=9,3, 17.3 Hz, 1H), 3,44 (1/2 of AB in ABX pattern, J=11,7, 17.3 Hz, 1H), 4,18 (kV, 2H), 5.25 in (X of ABX, 1H, J=9,3, to 11.9 Hz), 6,85 (DD, J=4,7, 7.7 Hz, 1H), 7,65 (DD, J=1,6, 7,8 Hz, 1H), 8,07 (DD, J=1,6, 4.8 Hz, 1H).

The following example 11 illustrates obtain ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-were)sulfonyl]oxy]-1H-pyrazole-5-carboxylate, which can be used to obtain ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate using techniques similar to the techniques described in example 10.

EXAMPLE 11

Obtain ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-were)sulfonyl]oxy]-1H-pyrazole-5-carboxylate

Triethylene is (3.75 g, to 37.1 mmol) was added dropwise to a mixture of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolecarboxylate (i.e. the product of example 8, stage A) (10.0 g, 37,1 mmol) and p-toluensulfonate (7,07 g, 37,1 mmol) in dichloromethane (100 ml) at 0°C. was Added an additional portion of the p-toluensulfonate (0.35 g, to 1.83 mmol) and triethylamine (0,19 g, 1.88 mmol). Then the reaction mixture was allowed to warm to room temperature and was stirred overnight. Then the mixture was diluted with dichloromethane (200 ml) and washed with water (3 x 70 ml). The organic phase was dried and evaporated, leaving specified in the header of the product as oil (13,7 g, yield 87%), which slowly formed crystals. The product was recrystallized from a mixture of ethyl acetate/hexane, melts at 99,5-100°C.

IR (nujol) ν: 1740, 1638, 1576, 1446, 1343, 1296, 1228, 1191, 1178, 1084, 1027, 948, 969, 868, 845 cm-1.

1H NMR (CDCl3) δ to 1.19 (t, 3H), of 2.45 (s, 3H), 3,12 (1/2 of AB in ABX pattern, J=17,3, 9 Hz, 1H), 3.33 and (1/2 of AB in ABX pattern, J=17,5, and 11.8 Hz, 1H), 4.16 the (q, 2H), 5,72 (X of ABX, J=9, 11.8 Hz, 1H), 6,79 (DD, J=4,6, and 7.7 Hz, 1H), was 7.36 (d, J=8,4 Hz, 2H), 7,56 (DD, J=1,6, 7,8 Hz, 1H), 7,95 (d, J=8,4 Hz, 2H), 8,01 (DD, J=1,4, 4.6 Hz, 1H).

EXAMPLE 12

Obtaining N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxamide

Stage A: Obtain ethyl 1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylate

To a suspension of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-PIR is Solidarnost (i.e. the product of example 8, stage (A) (27 g, 100 mmol), stir in dry acetonitrile (200 ml)was added sulfuric acid (20 g, 200 ml) in one portion. The reaction mixture was radigales with the formation of a pale green, almost transparent solution before thickening again with the formation of a pale yellow suspension. Was added potassium persulfate (33 g, 120 mmol) in one portion and the reaction mixture was heated under reflux for a relaxing reflux distilled for 3.5 hours. After cooling using baths with ice, the precipitated white solids were removed by filtration and discarded. The filtrate was diluted with water (400 ml) and then was extracted three times with ethyl ether (700 ml total). Concentration of the combined ether extracts to reduced volume (75 ml) caused the precipitation of solids not quite white (3.75 g), which was collected by filtration. The ethereal mother liquor was further concentrated to obtain a second batch of sludge is not quite white (4,2 g), which was also collected by filtration. The solid is not quite white was precipitated from the aqueous phase; it is solid (4.5 g) was collected by filtration to obtain in General, 12,45 g specified in the connection header.

1H NMR (DMSO-d6) δ of 1.06 (t, 3H), 4,11 (kV, 2H), 6,34 (s, 1H), and 7.6 (t, 1H), 8,19 (d, 1H), and 8.5 (d, 1H), 10,6 (s, 1H).

Stage: Received the e ethyl 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylate

To a suspension of ethyl 1-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-1H-pyrazole-5-carboxylate (i.e. the product of stage A) (0.8 g, 3 mmol), stir in dry acetonitrile (15 ml) at -5°With added potassium carbonate (0.85 grams, 6,15 mmol). The suspension was stirred for 15 minutes at 20°C. Then stirred suspension was cooled to 5aboutC and added dropwise 2,2,2-triftoratsetilatsetonom (0.8 g, of 3.45 mmol). The reaction mixture was heated to room temperature and then was heated under reflux for reflux distilled, after which thin layer chromatography showed complete reaction. To the reaction mixture were added water (25 ml) and then the mixture was extracted with ethyl ether. The ether extract was dried over magnesium sulfate and concentrated to obtain specified in the connection header-product of 1.05 g) as a pale yellow oil.

1H NMR (CDCl3) δ to 1.21 (t, 3H), 4,20 (kV, 2H), 4,63 (kV, 2H), 6,53 (s, 1H), and 7.4 (t, 1H), 7,9 (d, 1H), and 8.5 (d, 1H).

Stage C: Obtain 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylic acid

To a stirred solution of ethyl 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylate (i.e. the product of stage C) (0,92 g, 2.8 mmol) in methanol (15 ml) was added water (5 ml), which caused the turbidity of the reaction mixture. Was added dropwise an aqueous solution of sodium hydroxide (50%, 1.5 g, 19.2 mmol) and the reactions is nnow the mixture was stirred at room temperature for 30 minutes, moreover, during this period of time the reaction mixture became transparent again. Was added water (20 ml) and the reaction mixture was extracted with ethyl ether, which was discarded. The aqueous phase was acidified to pH 2 using concentrated hydrochloric acid and then was extracted with ethyl acetate (50 ml). An ethyl acetate extract was washed with water (20 ml) and brine (20 ml), dried over magnesium sulfate and concentrated to obtain specified in the title compound, isolated as a white solid (0.8 g).

1H NMR (DMSO-d6) δ and 4.9 (q, 2H), 6.75 in (s, 1H), and 7.6 (t, 1H), and 8.2 (d, 1H), 8,55 (d, 1H), 13,7 (USS, 1H).

Stage D: Obtain 6-chloro-8-methyl-2H-3,1-benzoxazin-2,4(1H)-dione

To a suspension of 2-amino-3-methyl-5-chlorbenzoyl acid (i.e. the product of example 1, stage A), (97 g, 520 mmol), stir in dry dioxane (750 ml) at room temperature was added dropwise trichloromethylcarbonate (63 g, 320 mmol). The reaction mixture exothermically heated slowly up to 42°S, and the solid is almost completely dissolved before again to form a thick slurry. After stirring the suspension at ambient temperature for 2.5 hours specified in the title compound was isolated by filtration, washed with ethyl ether and dried to obtain specified in the header of the value of the product, obtained as a white solid (98 g).

1H NMR (DMSO-d6) δ 2,3 (s, 3H), of 7.70 (s, 1H), of 7.75 (s, 1H), and 11.2 (s, 1H).

Stage E: Obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

To a suspension of 1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxylic acid (i.e. the product of stage (C) (7.9 g, 24 mmol), stirred in dichloromethane (100 ml)was added N,N-dimethylformamide (4 drops). Was added dropwise oxalicacid (4,45 g, 35 mmol) for 45 minutes. The resulting solution was stirred at room temperature for 4 hours and then concentrated in vacuum. The selected acid chloride acid was dissolved in dry acetonitrile (10 ml) was added to a suspension of 6-chloro-8-methyl-2H-3,1-benzoxazin-2,4(1H)-dione (i.e. the product of stage D) (4.9 g, 23 mmol), stir in dry acetonitrile (14 ml). Added pyridine (10 ml) and the solution was heated under reflux for reflux distilled for 6 hours. After cooling in a bath of ice collected precipitate white solids (9,15 g).1H-NMR-spectrum of the collected sediment showed peaks consistent with the presence specified in the header of the connection and residual starting material 6-chloro-8-methyl-2H-3,1-benzoxazin-2,4(1H)-dione. A small portion of the collected precipitate was recrystallized from acetonitrile to obtain net is shown in the header of the product, melting at 178-180°C.

1H NMR (DMSO-d6) δ 1,72 (s, 3H), 4,96 (kV, 2H),? 7.04 baby mortality (s, 1H), and 7.7 (t, 1H), of 7.75 (s, 1H), and 7.9 (s, 1H), 8.3 (l, 1H), and 8.6 (d, 1H).

Stage F: Obtaining N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-carboxamide

To a suspension of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-triptoreline)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it (i.e. product in the form of sediment stage E) (3,53 g, 7.5 mmol) in tetrahydrofuran (15 ml) was added dropwise methylamine (2.0 M solution in THF, 11 ml, 22 mmol)and the resulting solution was stirred at room temperature for 45 minutes. After this thin layer chromatography showed complete reaction. Was added ethyl ether (100 ml) and the reaction mixture was stirred for 2 hours at the sediment. The precipitate was collected by filtration and then recrystallized from acetonitrile to obtain white solids (0,82 g). The second game white solid (0.35 g) was besieged from a stock solution in acetonitrile and collected by filtration. The original mother liquor ether/tetrahydrofuran was concentrated to dryness and the remaining solid is recrystallized from acetonitrile to obtain third party white solid (0.95 g). These three parties were United with obtaining overall 2,12 g (after drying) is specified in the header connect the Oia, allocated in the form of a white solid, melting at 207-208°C.

1H NMR (CDCl3) δ to 2.18 (s, 3H), of 2.92 (d, 3H), of 4.66 (q, 2H), 6,15 (kV, 1H), and 6.6 (s, 1H), 7,2 (s, 1H), 7,25 (s, 1H), 7,35 (m, 1H), and 7.8 (d, 1H), 8,45 (d, 1H), 10.0 g (s, 1H).

Examples 13 and 14 illustrate alternative conditions of the reactions described in example 5, stage E, in example 3, stage E, respectively.

EXAMPLE 13

Getting 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-it

Methanesulfonamide (1.0 ml, 1.5 g, 13 mmol) was dissolved in acetonitrile (10 ml) and the mixture was cooled to -5°C. was Added dropwise a solution of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product pyrazolylborate acid of example 5, stage D) (3,02 g, 10 mmol) and pyridine (1.4 ml, 1.4 g, 17 mmol) in acetonitrile (10 ml) for 5 minutes at -5° - 0°C. During this addition was formed suspension. The mixture was stirred for 5 minutes at this temperature and then was added a mixture of 2-amino-3-methyl-5-chlorbenzoyl acid (i.e. the product of example 1, stage A) (1.86 g, 10 mmol) and pyridine (2.8 ml, 2.7 g, 35 mmol) in acetonitrile (10 ml), washing with additional acetonitrile (5 ml). This mixture was stirred for 15 minutes at -5° - 0°and then was added dropwise methanesulfonamide (1.0 ml, 1.5 ml, 13 mmol) in acetonitrile (5 ml) for 5 minutes at a temperature of -5°there - 0°C. the Reaction mixture was stirred for 15 minutes at this temperature, then the mixture was allowed to warm slowly to room temperature and was stirred for 4 hours. Was added dropwise water (20 ml) and the mixture was stirred for 15 minutes. Then the mixture was filtered, and the solids were washed with a mixture of 2:1 acetonitrile-water (3 x 3 ml), then acetonitrile (2 x 3 ml) and dried in nitrogen atmosphere to obtain specified in the header of the product as a pale yellow powder, 4,07 g (crude yield 90,2%), melting at 203-205°C. HPLC of this product using a chromatographic column Bond® RX-C8 (4.6 mm x 25 cm, eluent 25-95% acetonitrile/water, pH 3) showed the main peak corresponding specified in the header of the connection and having to 95.7% of the total area of the peaks of the chromatogram.

1H NMR (DMSO-d6) δ 1,72 (s, 3H), 7,52 (s, 1H), 7,72 for 7.78 (m, 2H), 7,88 (m, 1H), of 8.37 (DD, 1H), to 8.62 (DD, 1H).

EXAMPLE 14

Obtaining 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-it

Methanesulfonamide (1.0 ml, 1.5 g, 13 mmol) was dissolved in acetonitrile (10 ml) and the mixture was cooled to -5°C. was Added dropwise a solution of 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product of the carboxylic acid of example 3, stage D) (2.58 g, 10 mmol) and pyridine (1.4 ml, 1.4 g, 17 mmol) in acetonitrile (10 ml) for 5 mi the ut when -5° C - 0°C. During this addition was formed suspension. The mixture was stirred for 5 minutes at this temperature and then was added 2-amino-3-methyl-5-chlorobenzoyl acid (i.e. the product from example 1, stage A) (1.86 g, 10 mmol), the entire quantity immediately. Then was added dropwise a solution of pyridine (2.8 ml, 2.7 g, 35 mmol) in acetonitrile (10 ml) for 5 minutes at -5° - 0°C. the mixture was stirred for 15 minutes at -5° - 0°and then was added dropwise methanesulfonamide (1.0 ml, 1.5 ml, 13 mmol) in acetonitrile (5 ml) for 5 minutes at -5° - 0°C. the Reaction mixture was stirred for 15 minutes at this temperature, then allowed it to warm up slowly to room temperature and was stirred for 4 hours. Was added dropwise water (15 ml) and the mixture was stirred for 15 minutes. Then the mixture was filtered, and the solids were washed with a mixture of 2:1 acetonitrile-water (3 x 3 ml), then acetonitrile (2 x 3 ml) and dried in nitrogen atmosphere to obtain specified in the header of the product as a pale yellow powder, a 3.83 g (crude yield 94,0%), melting at 199-201°C. HPLC of this product using a chromatographic column Bond® RX-C8 (4.6 mm × 25 cm, eluent 25-95% acetonitrile/water, pH 3) showed a main peak corresponding to the specified header connection and having 97.8% of total space and peaks in the chromatogram.

1H NMR (DMSO-d6) δ 1,72 (s, 3H), of 7.48 (s, 1H), 7,74-7,80 (m, 2H), 7,87 (m, 1H), of 8.37 (DD, 1H), to 8.62 (DD, 1H).

EXAMPLE 15

Obtain 3-bromo-1-(3-chloro-1-oxido-2-pyridinyl)-N-[2,4-dichloro-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1H-pyrazole-5-carboxamide

3-bromo-1-(3-chloro-2-pyridinyl)-N-[2,4-dichloro-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1H-pyrazole-5-carboxamide (compound 25 is obtained by the method similar to the method of example 5, 487 mg, 0,916 mmol) was added to a mixture of methanol (1 ml) and methylene chloride (9 ml) followed by addition of 30%aqueous solution of N2O2(1 ml) and methyltrioxorhenium (VII) (0,100 g, 0,401 mmol). The reaction mixture was intensively stirred for 88 hours and after this time the reaction mixture were split between ethyl acetate and saturated aqueous NaHCO3. The combined organic extracts were dried (MgSO4), concentrated and purified according to the method of column chromatography to obtain specified in the header of the product compounds of the present invention in the form of a solid phase (54.8 mg), melting point 224-226°C.

1H NMR (DMSO) δ 1,02 (DD, 6N), 3,88 (DD, 1H), 7,44, (s, 1 H) 7,50-EUR 7.57 (m, 2H), 7,66 (d, 1H), 8,17 (d, NH), 7,83 (s, 1H), 10,51 (s, NH) at 8.36 (d, 1H).

Using techniques described herein using methods known in this field, can be obtained the following compounds of table 1. the tables which follow, have used the following abbreviations: t means tertiary, s means secondary, n means normal, i means ISO. Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl and Bu means butyl.

TABLE 1
R1R2R3R4aR4bR5R1R2R3R4aR4bR5
CH3FCF3MeHClClFCF3MeHCl
CH3FCF3EtHClClFCF3EtHCl
CH3FCF3i-PrHClClFCF3i-PrHCl
CH3FCF3t-BuHClClFCF3t-BuHCl
CH3FCF3MeMeClClFCF3MeMeCl
CH3FCF3MeHBrClFCF3MeHBr
CH3FCF3EtHBrClFCF3EtHBr
CH3FCF3i-PrHBrClFCF3i-PrHBr
CH3FCF3t-BuHBrClFCF3t-BuHBr
CH3F CF3MeMeBrClFCF3MeMeBr
CH3FClMeHClClFClMeHCl
CH3FClEtHClClFClEtHCl
CH3FCli-PrHClClFCli-PrHCl
CH3FClt-BuHClClFClt-BuHCl
CH3FClMeMeClClFClMeMeCl
CH3FClMeHBrClFClMe HBr
CH3FClEtHBrClFClEtHBr
CH3FCli-PrHBrClFCli-PrHBr
CH3FClt-BuHBrClFClt-BuHBr
CH3FClMeMeBrClFClMeMeBr
CH3FBrMeHClClFBrMeHCl
CH3FBrEtHClClFBrEtHCl
CH3FBri-PrHCl ClFBri-PrHCl
CH3FBrt-BuHClClFBrt-BuHCl

H
R1R2R3R4aR4bR5R1R2R3R4AR4bR5
CH3FBrMeMeClClFBrMeMeCl
CH3FBrMeHBrClFBrMeHBr
CH3FBrEtHBrClFBrEtHBr
CH3FBri-PrHBrl FBri-PrHBr
CH3FBrt-BuHBrClFBrt-BuHBr
CH3FBrMeMeBrClFBrMeMeBr
CH3FOch2CF3MeHClClFOch2CF3MeHCl
CH3FOch2CF3EtHClClFOch2CF3EtHCl
CH3FOch2CF3i-PrHClClFOch2CF3i-PrHCl
CH3FOch2CF3t-BuHClCl FOch2CF3t-BuHCl
CH3FOch2CF3MeMeClClFOch2CF3MeMeCl
CH3FOch2CF3MeHBrClFOch2CF3MeHBr
CH3FOch2CF3EtHBrClFOch2CF3EtHBr
CH3FOch2CF3i-PrHBrClFOch2CF3i-PrHBr
CH3FOch2CF3t-BuHBrClFOch2CF3t-BuHBr
CH3FCo2 CF3MeMeBrClFOch2CF3MeMeBr
CH3ClCF3MeHClClClCF3MeHCl
CH3ClCF3EtHClClClCF3EtHCl
CH3ClCF3i-PrHClClClCF3i-PrHCl
CH3ClCF3t-BuHClClClCF3t-BuHCl
CH3ClCF3MeMeClClClCF3MeMeCl
CH3ClCF3Me HBrClClCF3MeHBr
CH3ClCF3EtHBrClClCF3EtHBr
CH3ClCF3i-PrHBrClClCF3i-PrHBr
CH3ClCF3t-BuHBrClClCF3t-BuHBr
CH3ClCF3MeMeBrClClCF3MeMeBr
CH3ClClMeHClClClClMeHCl
CH3ClClEtHClClCl ClEtHCl
CH3ClCli-PrHClClClCli-PrHCl
CH3ClClt-BuHClClClClt-BuHCl
CH3ClClMeMeClClClClMeMeCl
CH3ClClMeHBrClClClMeHBr
CH3ClClEtHBrClClClEtHBr
CH3ClCli-PrHBrClClCli-PrHBr
CH3ClClt-BuBrClClClt-BuHBr
CH3ClClMeMeBrClClClMeMeBr
CH3ClBrMeHClClClBrMeHCl

R1R2R3R4AR4bR5R1R2R3R4aR4bR5
CH3ClBrEtHClClClBrEtHCl
CH3ClBri-PrHCIClClBri-PrHCl
CH3ClBrt-Bu HClClClBrt-BuHCl
CH3ClBrMeMeClClClBrMeMeCl
CH3ClBrMeHBrClClBrMeHBr
CH3ClBrEtHBrClClBrEtHBr
CH3ClBri-PrHBrClClBri-PrHBr
CH3ClBrt-BuHBrClClBrt-BuHBr
CH3ClBrMeMeBrClClBrMeMeBr
CH 3ClOch2CF3MeHClClClOch2CF3MeHCl
CH3ClOch2CF3EtHClClClOch2CF3EtHCl
CH3ClOch2CF3i-PrHClClClOch2CF3i-PrHCl
CH3ClOch2CF3t-BuHClClClOch2CF3t-BuHCl
CH3ClOch2CF3MeMeClClClOch2CF3MeMeCl
CH3ClOch2CF3MeHBrClCl Och2CF3MeHBr
CH3ClOch2CF3EtHBrClClOch2CF3EtHBr
CH3ClOch2CF3i-PrHBrClClOch2CF3i-PrHBr
CH3ClOch2CF3t-BuHBrClClOch2CF3t-BuHBr
CH3ClOch2CF3MeMeBrClClOch2CF3MeMeBr
CH3BrCF3MeHClClBrCF3MeHCl
CH3BrCF3EtH ClClBrCF3EtHCl
CH3BrCF3i-PrHClClBrCF3i-PrHCl
CH3BrCF3t-BuHClClBrCF3t-BuHCl
CH3BrCF3MeMeClClBrCF3MeMeCl
CH3BrCF3MeHBrClBrCF3MeHBr
CH3BrCF3EtHBrClBrCF3EtHBr
CH3BrCF3i-PrHBrCl BrCF3i-PrHBr
CH3BrCF3t-BuHBrClBrCF3t-BuHBr
CH3BrCF3MeMeBrClBrCF3MeMeBr
CH3BrClMeHClClBrClMeHCl
CH3BrClEtHClClBrClEtHCl
CH3BrCli-PrHClClBrCli-PrHCl
CH3BrClt-BnHClClBrClt-BuHCl
CH3 BrClMeMeClClBrClMeMeCl
CH3BrClMeHBrClBrClMeHBr
CH3BrClEtHBrClBrClEtHBr
CH3BrCli-PrHBrClBrCli-PrHBr

td align="center"> Br H
R1R2R3R4aR4bR5RlR2R3R4aR4bR5
CH3BrClt-BuHBrClBrClt-BuHBr
CH3ClMeMeBrClBrClMeMeBr
CH3BrBrMeHClClBrBrMeHCl
CH3BrBrEtHClClBrBrEtHCl
CH3BrBri-PrHClClBrBri-PrHCl
CH3BrBrt-BuHClClBrBrt-BuHCl
CH3BrBrMeMeClClBrBrMeMeCl
CH3BrBrMeHBrClBrBrMeBr
CH3BrBrEtHBrClBrBrEtHBr
CH3BrBri-PrHBrClBrBri-PrHBr
CH3BrBrt-BuHBrClBrBrt-BuHBr
CH3BrBrMeMeBrClBrBrMeMeBr
CH3BrOch2CF3MeHClClBrOch2CF3MeHCl
CH3BrOch2CF3EtHClClBrOch2CF3EtHCl
CH3 BrOch2CF3i-PrHClClBrOch2CF3i-PrHCl
CH3BrOch2CF3t-BuHClClBrOch2CF3t-BuHCl
CH3BrOch2CF3MeMeClClBrOch2CF3MeMeCl
CH3BrOch2CF3MeHBrClBrOch2CF3MeHBr
CH3BrOch2CF3EtHBrClBrOch2CF3EtHBr
CH3BrOch2CF3i-PrHBrClBrOch2CF 3i-PrHBr
CH3BrOch2CF3t-BuHBrClBrOch2CF3t-BuHBr
CH3BrOch2CF3MeMeBrClBrOch2CF3MeMeBr
CH3ICF3MeHClClICF3MeHCl
CH3ICF3EtHClClICF3EtHCl
CH3ICF3i-PrHClClICF3i-PrHCl
CH3ICF3t-BuHClClIF 3t-BuHCl
CH3ICF3MeMeClClICF3MeMeCl
CH3ICF3MeHBrClICF3MeHBr
CH3ICF3EtHBrClICF3EtHBr
CH3ICF3i-PrHBrClICF3i-PrHBr
CH3ICF3t-BuHBrClICF3t-BuHBr
CH3ICF3MeMeBrClICF3MeMe Br
CH3IClMeHClClIClMeHCl
CH3IClEtHClClIClEtHCl
CH3ICli-PrHClClICli-PrHCl
CH3IClt-BuHClClIClt-BuHCl
CH3IClMeMeClClIClMeMeCl

R1R2R3R4aR4bR5R1R2R3R4aR4bR5
CH3IClMeHBrClIClMeHBr
CH3IClEtHBrClIClEtHBr
CH3ICli-PrHBrClICli-PrHBr
CH3IClt-BuHBrClIClt-BuHBr
CH3IClMeMeBrClIClMeMeBr
CH3IBrMeHClClIBrMeHCl
CH3IBrEtHClCl IBrEtHCl
CH3IBri-PrHClClIBri-PrHCl
CH3IBrt-BuHClClIBrt-BuHCl
CH3IBrMeMeClClIBrMeMeCl
CH3IBrMeHBrClIBrMeHBr
CH3IBrEtHBrClIBrEtHBr
CH3IBri-PrHBrClIBri-PrHBr
CH3IBr t-BuHBrClIBrt-BuHBr
CH3IBrMeMeBrClIBrMeMeBr
CH3IOch2CF3MeHClClIOch2CF3MeHCl
CH3IOch2CF3EtHClClIOch2CF3EtHCl
CH3IOch2CF3i-PrHClClIOch2CF3i-PrHCl
CH3IOch2CF3t-BuHClClIOch2CF3t-BuHCl
CH3I Och2CF3MeMeClClIOch2CF3MeMeCl
CH3IOch2CF3MeHBrClIOch2CF3MeHBr
CH3IOch2CF3EtHBrClIOch2CF3EtHBr
CH3IOch2CF3i-PrHBrClIOch2CF3i-PrHBr
CH3IOch2CF3t-BuHBrClIOch2CF3t-BuHBr
CH3IOch2CF3MeMeBrClIOch2CF3 MeMeBr
CH3CF3CF3MeHClClCF3CF3MeHCl
CH3CF3CF3EtHClClCF3CF3EtHCl
CH3CF3CF3i-PrHClClCF3CF3i-PrHCl
CH3CF3CF3t-BuHClClCF3CF3t-BuHCl
CH3CF3CF3MeMeClClCF3CF3MeMeCl
CH3CF3CF3MeHBrCl CF3CF3MeHBr
CH3CF3CF3EtHBrClCF3CF3EtHBr
CH3CF3CF3i-PrHBrClCF3CF3i-PrHBr
CH3CF3CF3t-BuHBrClCF3CF3t-BuHBr
CH3CF3CF3MeMeBrClCF3CF3MeMeBr
CH3CF3ClMeHClClCF3ClMeHCl
CH3CF3ClEt HClClCF3ClEtHCl

R1R2R3R4aR4bR4R1R2R3R4aR4bR5
CH3CF3Cli-PrHClClCF3Cli-PrHCl
CH3CF3Clt-BuHClClCF3Clt-BuHCl
CH3CF3ClMeMeClClCF3ClMeMeCl
CH3CF3ClMeHBrClCF3ClMeHBr
CH3CF3ClEtHBrClCF3ClEtHBr
CH3CF3Cli-PrHBrClCF3Cli-PrHBr
CH3CF3Clt-BuHBrClCF3Clt-BuHBr
CH3CF3ClMeMeBrClCF3ClMeMeBr
CH3CF3BrMeHClClCF3BrMeHCl
CH3CF3BrEtHClClCF3BrEtHCl
CH3CF3 Bri-PrHClClCF3Bri-PrHCl
CH3CF3Brt-BuHClClCF3Brt-BuHCl
CH3CF3BrMeMeClClCF3BrMeMeCl
CH3CF3BrMeHBrClCF3BrMeHBr
CH3CF3BrEtHBrClCF3BrEtHBr
CH3CF3Bri-PrHBrClCF3Bri-PrHBr
CH3CF3Br HBrClCF3Brt-BuHBr
CH3CF3BrMeMeBrClCF3BrMeMeBr
CH3CF3Och2CF3MeHClClCF3Och2CF3MeHCl
CH3CF3Och2CF3EtHClClCF3Och2CF3EtHCl
CH3CF3Och2CF3i-PrHClClCF3Och2CF3i-PrHCl
CH3CF3Och2CF3t-BuHClClCF3Och2CF3t-Bu HCl
CH3CF3Och2CF3MeMeClClCF3Och2CF3MeMeCl
CH3CF3Och2CF3MeHBrClCF3Och2CF3MeHBr
CH3CF3Och2CF3EtHBrClCF3Och2CF3EtHBr
CH3CF3Och2CF3i-PrHBrClCF3Och2CF3i-PrHBr
CH3CF3Och2CF3t-BuHBrClCF3Och2CF3t-BuHBr
CH3/td> CF3Och2CF3MeMeBrClCF3Och2CF3MeMeBr
CH3ClCln-PrHClClClCln-PrHCl
CH3ClCln-BuHClClClCln-BuHCl
CH3ClCls-BuHClClClCls-BuHCl
CH3ClCli-BuHClClClCli-BuHCl
CH3ClClEtMeClClClClEtMeCl
FFCF3MeH ClBrFCF3MeHCl
FFCF3EtHClBrFCF3EtHCl
FFCF3i-PrHClBrFCF3i-PrHCl
FFCF3t-BuHClBrFCF3t-BuHCl

t-Bu
R1R2R3R4AR4bR5R1R2R3R4aR4bR5
FFCF3MeMeClBrFCF3MeMeCl
FFCF3 MeHBrBrFCF3MeHBr
FFCF3EtHBrBrFCF3EtHBr
FFCF3i-PrHBrBrFCF3i-PrHBr
FFCF3t-BuHBrBrFCF3t-BuHBr
FFCF3MeMeBrBrFCF3MeMeBr
FFClMeHClBrFClMeHCl
FFClEtHClBrFClEtH Cl
FFCli-PrHClBrFCli-PrHCl
FFClt-BuHClBrFClt-BuHCl
FFClMeMeClBrFClMeMeCl
FFClMeHBrBrFClMeHBr
FFClEtHBrBrFClEtHBr
FFCli-PrHBrBrFCli-PrHBr
FFClt-BuHBrBrFClt-BuH Br
FFClMeMeBrBrFClMeMeBr
FFBrMeHClBrFBrMeHCl
FFBrEtHClBrFBrEtHCl
FFBri-PrHClBrFBri-PrHCl
FFBrt-BuHClBrFBrt-BuHCl
FFBrMeMeClBrFBrMeMeCl
FFBrMeHBrBrFBrMeH Br
FFBrEtHBrBrFBrEtHBr
FFBri-PrHBrBrFBri-PrHBr
FFBrt-BuHBrBrFBrt-BuHBr
FFBrMeMeBrBrFBrMeMeBr
FFOch2CF3MeHClBrFOch2CF3MeHCl
FFOch2CF3EtHClBrFOch2CF3EtHCl
FFOch2CF3i-PrH ClBrFOch2CF3i-PrHCl
FFOch2CF3t-BuHClBrFOch2CF3t-BuHCl
FFOch2CF3MeMeClBrFOch2CF3MeMeCl
FFOch2CF3MeHBrBrFOch2CF3MeHBr
FFOch2CF3EtHBrBrFOch2CF3EtHBr
FFOch2CF3i-PrHBrBrFOch2CF3i-PrHBr
FFOch2CF3HBrBrFOch2CF3t-BuHBr
FFOch2CF3MeMeBrBrFOch2CF3MeMeBr
FClCF3MeHClBrClCF3MeHCl

R1R2R3R4aR4bR5R1R2R3R4AR4bR5
FClCF3EtHClBrClCF3EtHCl
FClCF3i-PrHClBrClCF3i-PrHCl
FCICF3t-BuHClBrClCF3t-BuHCl
FClCF3MeMeClBrClCF3MeMeCl
FClCF3MeHBrBrClCF3MeHBr
FClCF3EtHBrBrClCF3EtHBr
FClCF3i-PrHBrBrClCF3i-PrHBr
FClCF3t-BuHBrBrClCF3t-BuHBr
FClCF3MeMe BrBrClCF3MeMeBr
FClClMeHClBrClClMeHCl
FCIClEtHClBrClClEtHCl
FClCli-PrHClBrClCli-PrHCl
FClClt-BuHClBrClClt-BuHCl
FClClMeMeClBrClClMeMeCl
FClClMeHBrBrClClMeHBr
FClClEt/td> HBrBrClClEtHBr
FClCli-PrHBrBrClCli-PrHBr
FClClt-BuHBrBrClClt-BuHBr
FClClMeMeBrBrClClMeMeBr
FClBrMeHClBrClBrMeHCl
FClBrEtHClBrClBrEtHCl
FClBri-PrHClBrClBri-PrHCl
FClBr t-BuHClBrClBrt-BuHCl
FClBrMeMeClBrClBrMeMeCl
FClBrMeHBrBrClBrMeHBr
FClBrEtHBrBrClBrEtHBr
FClBri-PrHBrBrClBri-PrHBr
FClBrt-BuHBrBrClBrt-BuHBr
FClBrMeMeBrBrClBrMeMeBr
FClOS is 2CF3MeHClBrClOch2CF3MeHCl
FClOch2CF3EtHClBrClOch2CF3EtHCl
FClOch2CF3i-PrHClBrClOch2CF3i-PrHCl
FClOch2CF3t-BuHClBrClOch2CF3t-BuHCl
FClOch2CF3MeMeClBrClOch2CF3MeMeCl
FClOch2CF3MeHBrBrClOch2CF3MeHBr
FClOch2CF3EtHBrBrClOch2CF3EtHBr
FClOch2CF3i-PtHBrBrClOch2CF3i-PrHBr

Br Brtd align="center"> Br
R1R2R3R4AR4bR5R1R2R3R4aR4bR5
FClOch2CF3t-BuHBrBrClOch2CF3t-BuHBr
FClOch2CF3MeMeBrBrClOch2CF3MeMeBr
FBrCF3MeH ClBrBrCF3MeHCl
FBrCF3EtHClBrBrCF3EtHCl
FBrCF3i-PrHClBrBrCF3i-PrHCl
FBrCF3t-BuHClBrBrCF3t-BuHCl
FBrCF3MeMeClBrBrCF3MeMeCl
FBrCF3MeHBrBrBrCF3MeHBr
FBrCF3EtHBrBrBrCF3EtH Br
FBrCF3i-PrHBrBrBrCF3i-PrHBr
FBrCF3t-BuHBrBrBrCF3t-BuHBr
FBrCF3MeMeBrBrBrCF3MeMeBr
FBrClMeHClBrBrClMeHCl
FBrClEtHClBrBrClEtHCl
FBrCli-PrHClBrBrCli-PrHCl
FBrClt-BuHClBrClt-BuHCl
FBrClMeMeClBrBrClMeMeCl
FBrClMeHBrBrBrClMeHBr
FBrClEtHBrBrBrClEtHBr
FBrCli-PrHBrBrBrCli-PrHBr
FBrClt-BuHBrBrBrClt-BuHBr
FBrClMeMeBrBrBrClMeMeBr
FBrBrMeHClBrBrMeHCl
FBrBrEtHClBrBrBrEtHCl
FBrBri-PrHClBrBrBri-PrHCl
FBrBrt-BuHClBrBrBrt-BuHCl
FBrBrMeMeClBrBrBrMeMeCl
FBrBrMeHBrBrBrBrMeHBr
FBrBrEtHBrBrBrBrEtHBr
FBrBri-PrHBrBrBri-PrHBr
FBrBrt-BuHBrBrBrBrt-BuHBr
FBrBrMeMeBrBrBrBrMeMeBr
FBrOch2CF3MeHClBrBrOch2CF3MeHCl
FBrOch2CF3EtHClBrBrOch2CF3EtHCl
FBrOch2CF3i-PrHClBrBrOch2CF3i-PrHCl
FBrOch2CF3t-BuHClBrBrOch2CF3 t-BuHCl
FBrOch2CF3MeMeClBrBrOch2CF3MeMeCl

F
R1R2R3R4aR4bR5R1R2R3R4aR4bR5
FBrOch2CF3MeHBrBrBrOch2CF3MeHBr
FBrOch2CF3EtHBrBrBrOch2CF3EtHBr
FBrOch2CF3i-PrHBrBrBrOch2CF3i-PrHBr
FBr Och2CF3t-BuHBrBrBrOch2CF3t-BuHBr
FBrOch2CF3MeMeBrBrBrOch2CF3MeMeBr
FICF3MeHClBrICF3MeHCl
FICF3EtHClBrICF3EtHCl
FICF3i-PrHClBrICF3i-PrHCl
FICF3t-BuHClBrICF3t-BuHCl
FICF3MeMe ClBrICF3MeMeCl
FICF3MeHBrBrICF3MeHBr
FICF3EtHBrBrICF3EtHBr
FICF3i-PrHBrBrICF3i-PrHBr
FICF3t-BuHBrBrICF3t-BuHBr
FICF3MeMeBrBrICF3MeMeBr
FIClMeHClBrIClMeHCl
IClEtHClBrIClEtHCl
FICli-PrHClBrICli-PrHCl
FIClt-BuHClBrIClt-BuHCl
FIClMeMeClBrIClMeMeCl
FIClMeHBrBrIClMeHBr
FIClEtHBrBrIClEtHBr
FICli-PrHBrBrICli-PrHBr
FIClt-BuHBrBrIClt-BuHBr
FIClMeMeBrBrIClMeMeBr
FIBrMeHClBrIBrMeHCl
FIBrEtHClBrIBrEtHCl
FIBri-PrHClBrIBri-PrHCl
FIBrt-BuHClBrIBrt-BuHCl
FIBrMeMeClBrIBrMeMeCl
FIBrMeHBrBrIBrMeHBr
FIBrEtHBrBrIBrEtHBr
FIBri-PrHBrBrIBri-PrHBr
FIBrt-BuHBrBrIBrt-BuHBr
FIBrMeMeBrBrIBrMeMeBr
FIOch2CF3MeHClBrIOch2CF3MeHCl
FIOch2CF3EtHClBrIOch2 CF3EtHCl

Br
R1R2R3R4aR4bR5R1R2R3R4aR4bR5
FIOch2CF3i-PrHClBrIOch2CF3i-PrHCl
FIOch2CF3t-BuHClBrIOch2CF3t-BuHCl
FIOch2CF3MeMeClBrIOch2CF3MeMeCl
FIOch2CF3MeHBrBrIOch2CF3MeHBr
F IOch2CF3EtHBrBrIOch2CF3EtHBr
FIOch2CF3i-PrHBrBrIOch2CF3i-PrHBr
FIOch2CF3t-BuHBrBrIOch2CF3t-BuHBr
FIOch2CF3MeMeBrBrIOch2CF3MeMeBr
FCF3CF3MeHClBrCF3CF3MeHCl
FCF3CF3EtHClBrCF3CF3EtHCl
FCF3CF3i-PrHClBrCF3CF3i-PrHCl
FCF3CF3t-BuHClBrCF3CF3t-BuHCl
FCF3CF3MeMeClBrCF3CF3MeMeCl
FCF3CF3MeHBrBrCF3CF3MeHBr
FCF3CF3EtHBrBrCF3CF3EtHBr
FCF3CF3i-PrHBrBrCF3CF3i-PrHBr
FCF3CF3t-BuHBrBrCF3CF3t-BuHBr
FCF3CF3MeMeBrBrCF3CF3MeMeBr
FCF3ClMeHClBrCF3ClMeHCl
FCF3ClEtHClBrCF3ClEtHCl
FCF3Cli-PrHClBrCF3Cli-PrHCl
FCF3Clt-BuHClBrCF3Clt-BuHCl
FCF3 MeMeClBrCF3ClMeMeCl
FCF3ClMeHBrBrCF3ClMeHBr
FCF3ClEtHBrBrCF3ClEtHBr
FCF3Cli-PrHBrBrCF3Cli-PrHBr
FCF3Clt-BuHBrBrCF3Clt-BuHBr
FCF3ClMeMeBrBrCF3ClMeMeBr
FCF3BrMeHClBrCF3MeHCl
FCF3BrEtHClBrCF3BrEtHCl
FCF3Bri-PrHClBrCF3Bri-PrHCl
FCF3Brt-BuHClBrCF3Brt-BuHCl
FCF3BrMeMeClBrCF3BrMeMeCl
FCF3BrMeHBrBrCF3BrMeHBr
FCF3BrEtHBrBrCF3BrEtHBr
FCF3/sub> Bri-PrHBrBrCF3Bri-PrHBr
FCF3Brt-BuHBrBrCF3Brt-BuHBr

R1R2R3R4AR4bR5R1R2R3R4aR4bR5
FCF3BrMeMeBrBrCF3BrMeMeBr
FCF3Och2CF3MeHClBrCF3Och2CF3MeHCl
FCF3Och2CF3EtHClBrCF3 Och2CF3EtHCl
FCF3Och2CF3i-PrHClBrCF3Och2CF3i-PrHCl
FCF3Och2CF3t-BuHClBrCF3Och2CF3t-BuHCl
FCF3Och2CF3MeMeClBrCF3Och2CF3MeMeCl
FCF3Och2CF3MeHBrBrCF3Och2CF3MeHBr
FCF3Och2CF3EtHBrBrCF3Och2CF3EtHBr
FCF3 Och2CF3i-PrHBrBrCF3Och2CF3i-PrHBr
FCF3Och2CF3t-BuHBrBrCF3Och2CF3t-BuHBr
FCF3Och2CF3MeMeBrBrCF3Och2CF3MeMeBr

As shown in figure 1 and is additionally illustrated in examples 1-10, the benzoxazines of formula 2, such as listed in table 2 are applicable for producing compounds of formula 1, including the compounds listed in table 1.

TABLE 2
R1R2R3R5R1R2R3R5
CH3F CF3ClClFCF3Cl
CH3FCF3BrClFCF3Br
CH3FClClClFClCl
CH3FClBrClFClBr
CH3FBrClClFBrCl
CH3FBrBrClFBrBr
CH3FOch2CF3ClClFOch2CF3Cl
CH3FOch2CF3BrClFOch2CF3Br
CH3ClCF3ClClClCF3Cl
CH ClCF3BrClClCF3Br
CH3ClClClClClClCl

R1R2R3R5R1R2R3R5
CH3ClClBrClClClBr
CH3ClBrClClClBrCl
CH3ClBrBrClClBrBr
CH3ClOch2CF3ClClClOch2CF3Cl
CH3ClOch2CF3BrClClOch2CF3Br
CH3Br CF3ClClBrCF3Cl
CH3BrCF3BrClBrCF3Br
CH3BrClClClBrClCl
CH3BrClBrClBrClBr
CH3BrBrClClBrBrCl
CH3BrBrBrClBrBrBr
CH3BrOch2CF3ClClBrOch2CF3Cl
CH3BrOch2CF3BrClBrOch2CF3Br
CH3ICF3ClClICF3Cl
CH3ICF3BrClICF3Br
CH3IClClClIClCl
CH3IClBrClIClBr
CH3IBrClClIBrCl
CH3IBrBrClIBrBr
CH3IOch2CF3ClClIOch2CF3Cl
CH3IOch2CF3BrClIOch2CF3Br
CH3CF3CF3ClClCF3CF3Cl
CH3CF3CF3BrClCFsub> 3CF3Br
CH3CF3ClClClCF3ClCl
CH3CF3ClBrClCF3ClBr
CH3CF3BrClClCF3BrCl
CH3CF3BrBrClCF3BrBr
CH3CF3Och2CF3ClClCF3Och2CF3Cl
CH3CF3Och2CF3BrClCF3Och2CF3Br
FFCF3ClBrFCF3Cl
FFCF3BrBrFCF3 Br
FFClClBrFClCl
FFClBrBrFClBr
FFBrClBrFBrCl
FFBrBrBrFBrBr
FFOch2CF3ClBrFOch2CF3Cl
FFOch2CF3BrBrFOch2CF3Br

R1R2R3R5R1R2R3R5
FClCF3ClBrClCF3Cl
FClCF3BrBr ClCF3Br
FClClClBrClClCl
FClClBrBrClClBr
FClBrClBrClBrCl
FClBrBrBrClBrBr
FClOch2CF3ClBrClOch2CF3Cl
FClOch2CF3BrBrClOch2CF3Br
FBrCF3ClBrBrCF3Cl
FBrCF3BrBrBrCF3Br
FBrClClBrBrClCl
FBrClBrBrBrClBr
FBrBrClBrBrBrCl
FBrBrBrBrBrBrBr
FBrOch2CF3ClBrBrOch2CF3Cl
FBrOch2CF3BrBrBrOch2CF3Br
FICF3ClBrICF3Cl
FICF3BrBrICF3Br
FIClClBrIClCl
FIClBrBrIClBr
FIBrClr IBrCl
FIBrBrBrIBrBr
FIOch2CF3ClBrIOch2CF3Cl
FIOch2CF3BrBrIOch2CF3Br
FCF3CF3ClBrCF3CF3Cl
FCF3CF3BrBrCF3CF3Br
FCF3ClClBrCF3ClCl
FCF3ClBrBrCF3ClBr
FCF3BrClBrCF3BrCl
FCF3Br BrBrCF3BrBr
FCF3Och2CF3ClBrCF3Och2CF3Cl
FCF3Och2CF3BrBrCF3Och2CF3Br

As shown in scheme 2 and is additionally illustrated in examples 1-10, pyrazolylborate acid of formula 4, such as listed in table 3, applicable in obtaining the compounds of formula 1, including the compounds listed in table 1.

TABLE 3
R3R5R3R5&3R5
CF3ClOch2CF3ClBrBr
ClClCF3BrOch2CF3Br
BrClClBr

The preparation of compositions/applicability

The compounds of this invention typically will be used in the form of ready-made forms or compositions with acceptable agricultural carrier containing at least one liquid diluent, a solid diluent or a surfactant. The ingredients ready form or composition is chosen in such a way that they are compatible with the physical properties of the active ingredient, route of administration and environmental factors such as soil type, moisture and temperature. Applicable forms include liquids, such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspension-emulsion) or the like, which may be optionally thickened with the formation of gels. In addition, applicable forms include solids, such as dusty, powders, granules, beads, tablets, films, etc. that may be water-dispersible ("wet") or water-soluble. The active ingredient may be (micro)encapsulated and additionally prepared in the form of a suspension or solid form; alternatively, all finished form of the active ingredient can be encapsulated or enclosed in protective coating"). Encapsulation may regulate the work or delay the release of the active ingredient. Suitable for spray compositions can be distributed in suitable media and used in amounts of aerosols from about one to several hundred liters per hectare. Compositions with a high concentration are primarily used as intermediates for the further preparation of the ready-made forms.

Ready-made forms usually contain an effective amount of the active ingredient, diluent and surfactant in the following approximate ranges that are added to 100 percent by weight.

The percentage by weight (wt.%)
The active ingredientThinnerSurfactant
Water-dispersible and water-soluble granules, tablets and powders5-900-941-15
Suspensions, emulsions, solutions (including emulsifiable concentrates)5-5040-950-15
Dusty1-2570-990-5
Pellets and balls0,01-995-99,990-15
The composition of the high concentration90-990-10 0-2

Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2ndEd., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2ndEd., Interscience, New York, 1950. McCutcheon''s Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All forms can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth, etc. or thickeners to increase the viscosity.

Surfactants include, for example, polyethoxysiloxane alcohols, polyethoxysiloxane ALKYLPHENOLS, polyethoxysiloxane esters of fatty acids sorbitan, diallylmalonate, alkyl sulphates, alkylbenzenesulfonate, organosilicone, N,N-dialkylamide, ligninsulfonate, condensates of naphthalenesulfonate-formaldehyde, polycarboxylate and block copolymers of polyoxyethylene and polyoxypropylene. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silicon dioxide, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and sodium bicarbonate and sodium sulfate. Liquid diluents include, for example, water, N,N-digitiform the Ministry of foreign Affairs, dimethyl sulfoxide, N-alkylpyridine, ethylene glycol, polypropyleneglycol, polypropenkarbonat, esters of dibasic acids, paraffins, alkyl benzenes, alkylnaphthalene, olive, castor, linseed, Tung, sesame, corn, peanut, cottonseed, soybean, responae and coconut oil, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols, such as methanol, cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol.

Solutions, including emulsifiable concentrates can be prepared by simple mixing of the ingredients. Dusty and powders can be prepared by mixing and usually by grinding, for example, in a hammer mill or a jet mill. Suspensions are usually prepared by wet milling (pan grinder mill wet grinding); see, for example, U.S. patent 3060084. Granules and beads can be prepared by spraying the active material on the pre-formed granular carriers or by agglomeration. Cm. Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp.147-48, Perry's Chemical Engineer''s Handbook, 4thEd., McGraw-Hill, New York, 1963, pages 8-57 and following pages, and PCT Publication WO 91/13546. Beads can be prepared as described in U.S. patent 4172714. Water-dispersible and water-soluble granules can be prepared as described in patents Usawith rooms 4144050, 3920442 and German patent 3246493. Tablets can be prepared as described in U.S. patent numbers 5180587, 5232701 and 5208030. Films can be prepared as described in UK patent 2095558 and U.S. patent 3299566.

For further information concerning preparation areas, see T.S.Woods, "The Formulator''s Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T.Brooks and T.R.Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp.120-133. Cm. also U.S. 3235361, Column 6, line 16 to Column 7, line 1-9 and examples 10-41; U.S. 3309192, Column 5, line 43 to Column 7, line 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2891855, Column 3, line 66 to Column 5, line 17 and examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

In the following examples, all percentages are percentages by weight (wt.%) all forms are prepared in a common manner. Rooms compounds refer to compounds in Index Table A.

Example a
Wettable powder
Connection 265,0%
ether dodecylphenol and polyethylene glycol2,0%
lignin is ulpanat sodium 4,0%
silicoaluminate sodium6,0%
montmorillonite (calcinated)23,0%
The example In
Pellet
Connection 1010,0%
granules attapulgite (low-volatile material90,0%
of 0.71/0.30 mm; U.S.S. sieve No. 25-50)
Example
Extruded bead
The connection 2025,0%
anhydrous sodium sulfate10,0%
untreated ligninsulfonate calcium5,0%
alkylnaphthalene sodium1,0%
calcium/magnesium bentonite59,0%
Example D
Emulsifiable concentrate
The connection 3320,0%
the mixture is soluble in the oil sulfonates and polyoxyethylene esters10,0%
Isophorone70,0%

Connection on the frame of the invention differ favorable nature of the metabolic and/or soil residual distribution and find activity suppression spectrum of agricultural and non-agricultural invertebrates pests. In this context, the expression "the suppression of invertebrate pests" means the inhibition of the development of invertebrate pests (including killing), which causes a significant reduction in eating or other damage or damage caused by these pests; and related expressions are defined similarly). The term "invertebrate pest"as used in this invention includes arthropods, gastropods and nematodes (roundworms) economic importance as pests. The term "arthropods" (Arthropoda includes insects, mites, spiders, Scorpions, Gubanova (centipedes), of, woodlice and simpill. The term "gastropods" (Gastropoda includes snails, slugs and other Stylommatophora. The term "nematode" (roundworms) includes worms, such as roundworms, worms, parasitic in the heart, and herbivorous nematodes (Nematoda), flukes (Trematoda), skrebni (Acanthocephala) and tapeworms (Cestoda). Professionals in this field should be clear that not all compounds are equally effective against all pests. The compounds of this invention display activity against economically important agricultural and non-agricultural pest. The term "agriculture" refers to products which olewig cultures, for example, for food and fiber, and includes the cultivation of cereal crops (e.g. wheat, oats, barley, rye, rice, maize), soybeans, vegetable crops (for example, salad of lettuce, cabbage, tomatoes, beans), potatoes, sweet potatoes (yams), grapes, cotton, and receiving the fruits of fruit trees (e.g., fleshy (pome fruit, stone fruit (Kotenok) and citrus fruits or wild orange crops). The term "non-agricultural" refers to other horticultural plants (e.g., forest, greenhouse plants grown in nurseries plants or ornamental plants not growing in the field), public health (human) and animal health agencies for animal domestication and commercial structures, to the household and to applications for stored products or pests. Given the wide range of suppression of invertebrate pests and economic importance of protection from loss or damage caused by invertebrate pests) crops of cotton, corn, soybean, rice, vegetables, potatoes, sweet potatoes (yams), grape fruits and fruit trees by destroying the invertebrate pest is a preferred variant of the present invention. Agricultural or Gesellschaften the e pests include the larvae (caterpillars) Lepidoptera (Lepidoptera (butterflies and moths)), such as "marching (feat) worms", i.e. the larvae of some insects, forming large, motile clusters), insects, podgryzayuschie plants, the geometrid moths and moths in the family Noctuidae (e.g., scoop herbal (Spodoptera fugiperda J.E. Smith), scoop a small (Spodoptera exigua Hübner), scoop Upsilon (Agrotis ipsilon Hufnagel), cabbage moth (scoop) (Trichoplusia ni Hübner), bollworm tobacco (Heliothis virescens Fabricius)); svalilsya (grinders), czechanski, caterpillars building a spider nest, conical worms, mermaidy (Mermithidae) and pests, skeletonema leaves (leaving only veins), from the family Pyralidae (e.g., corn borer (Ostrinia nubilalis Hübner), caterpillar, striking orange navel (navel orange) (Amyelois transitella Walker), scoop fire (Crambus caliginosellus Clemens), the beet webworm (Herpetogramma licarsisalis Walker)); leafrollers, leafroller caterpillars-Packed and caterpillar pests of seeds and caterpillars are pests of fruit (of the Codling moth in the family Tortricidae (e.g., moth Codling (Cydia pomonella Linnaeus), grape moth (Endopiza viteana Clemens), tortrix Oriental peach (Grapholita molesta Busck)); and many other economically important Lepidoptera (e.g., the cabbage moth (Plutella xylostella Linnaeus), pink boxed worm of cotton (Pectinophora gossypiella Saunders), Gypsy moth (naparnik) (Lymantria dispar Linnaeus)); nymphs and adults of troop Blattodea (Cockroaches), including cockroaches from the families Blattellidae and Battidae (for example, the black cockroach (Blatta orientalis Linnaeus), Asian cockroach (Blatella asahinai Mizukubo), cockroach red (Prusak) (Blattella germanica Linnaeus), brown cockroach-striped (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunnea Burmeister), Madeira cockroach (Leucophaea madera Fabricius)); feeding on foliage caterpillars and adults of the order of Coleoptera (beetles), including weevils (elephants) from the families Anthribidae, Bruchidae, and Curculionidae (e.g., the weevil cotton (Anthonomus grandis Boheman), weevil rice water (Lissorhoptrus oryzophilus Kuschel), granary weevil (elephant grain) (Sitophilus granarius Linnaeus), rice weevil (Sitophillus oryzae Linnaeus)); excavation (truck) midges, beetles flea beetle cucumber, leaf-koreeda, leaf beetles, potato beetles and leaf-mining flies (flies miners) in the family Chrysomelidae (e.g., Colorado potato beetle (Leptinotarsa decemlineata Say), blocka corn (Diabrotica virgifera virgifera LeConte)); Khrushchev and other beetles from the family Scaribaeidae (for example, garden chafer Japanese (Popillia Japonica Newman) and garden chafer European (Rhizotrogus majalis Razoumowsky)); koreeda from the family Dermestidae; click beetles of the family Elateridae; bark beetles from the family Scolytidae and larval large flour from the family Tenebrionidae. In addition, agricultural and non-agricultural pests include: adults and larvae (caterpillars) detachment Dermaptera (earwig), including earwigs from the family Forficulidae (e.g., whoverse byknowing (Forficula auricularia Linnaeus), whoverse black (Chelisoches morio Fabricius)); adults and nymphs of units Hemiptera (Heteroptera (bugs)and Homoptera (ramnarine), such as bugs-kanaky from the family Miridae, cicadas from the family Cicadidae, cycatki (e.g., Empoasca spp.) their family Cicadellidae, locusts and delphacidae of families Fulgoroidae and Delphacidae, the humpback from the family Membracidae, listblock from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae, mealybugs (walochnik) from the family Pseudococcidae, scales (scale insects) of the families Coccidae, Diaspididae and Margarodidae, bugs lacemakers from the family Tingidae, bugs-defenders of the family Pentatomidae, white-winged bugs (e.g., Blissus spp.) and other pests of seeds from the family Lygaeidae, pennisi from the family Cercopidae, bugs pumpkin from the family Coreidae, and krasnolipe and krasnolipe cotton from the family Pyrrhocoridae. In the list of pests also included are adults and larvae of detachment Acari (aerovee mites)such as spider mites and red mites in the family Tetranychidae (e.g., European red mite (Panonychus ulmi Koch), mite bimaculated spider mites (Tetranychus urticae Koch), the tick of Macdaniel (Tetranychus mcdanieli McGregor)), plastinki in the family Tenuipalpidae (e.g., plasmatica citrus (Brevipalpus lewisi McGregor)), ticks haloorange and Bud in the family Eriophydae and other eating foliage ticks and mites that affect the health of humans and animals,i.e. the house dust mites in the family Epidermoptidae, zeleznice (ugritsy) in the family Demodicidae, grain mites in the family Glycyphagidae, ticks Ixodes ticks in the family Ixodidae (e.g., deer tick (Ixodes scapularis Say), tick paralysis Australian (Ixodes holocyclus Neumann), the tick American dog (Dermacentor variabilis Say), tick amblyomma (Amblyomma americanum Linnaeus) and horse ticks and mites cestocide in the families Psoroptidae, Pyemotidae, and Sarcotidae; adults and not fully developed specimens of Orthoptera order (Orthoptera), including kuznechikova, locusts and crickets (e.g., locusts Mexican (e.g., Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American locust (e.g., Schistocerca americana Drury), desert locust (Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), house cricket (Acheta domesticus Linnaeus), mole crickets common cancers (earthen) (Gryllotalpa spp.)); adult and not fully developed individuals detachment Diptera (flies), including leaf-mining flies, midges, fruit flies (Tephritidae), Swedish fly (e.g., Oscinella frit Linnaeus), soil maggots of flies, flies bedroom (e.g., Musca domestica Linnaeus), flies small room (e.g., Fannia canicularis Linnaeus, F. femoralis Stein), jagalchi ordinary (jagalchi autumn) (for example, Stomoxis calcitrans Linnaeus), flies autumn, jagalchi cow small, flies blue meat (e.g., Chrysomya spp., Phormia spp.), and other true flies, pests, horse botflies (e.g., Tabanus spp.), botflies nasopharyngeal horse is s (for example, Gastrophilus spp., Oestrus spp.), larvae bullish striped gadfly (e.g., Hypoderma spp.), flies deer (e.g., Chrysops spp.), Keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera (korotkoe), mosquitoes (mosquitoes) (for example, Aedes spp., Anopheles spp., Culex spp.), Midge black (e.g., Prosimulium spp., Simulium spp.), biting biting midges, black flies, gnats, and other Nematocera; adults and not fully developed individuals detachment Thysanoptera (thrips), including onion thrips (tobacco) (Thrips tabaci Lindeman) and other eating leaves thrips; insect pests of the order Hymenoptera (Hymenoptera), including ants (for example, ant-tree-borer, red (Camponotus ferruginous Fabricius), the ant-tree-borer, black (Camponotus pennsylvanicus De Geer), Pharaoh ant (Monomorium pharaonis Linnaeus), Tasmania (Wasmannia auropunctata Roger), ant Richter (Solenopsis geminata Fabricius), ant forest red (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), paratrechina (Paratrechina longicornis Latreille), ant sod (Tetramorium caespitum Linnaeus), lazy American (Lasius alienus Forster), ant odorous house (Tapinoma sessile Say)), bees (including bees-the carpenters), hornets, Golden jacks and wasps; insect pests of the detachment Isoptera (termites), including termite yellow-footed Mediterranean (Reticulitermes flavipes Kollar), termite Western Mediterranean (Reticulitermes hesperus Banks), termite Mediterranean Taiwan (Coptotermes formosanus Shiraki), termite drevoedy West Indian (Incisitermes immigrans Snyder) and other termite the economic values; insect pests of detachment Thysanura (Seinajoki), such as Chechulina ordinary (Lepisma saccharina Linnaeus) and Chechulina home (Thermobia domestica Packard); insect pests of the detachment Mallophaga (hematophagous biting) and including the head louse (Pediculus humanus capitis De Geer), a louse (Pediculus humanus humanus Linnaeus), pakhoed (Menacanthus stramineus Nitszsch), dog louse (Trichodectes canis De Geer), pogoed chicken pertrovskiy (Goniocotes gallinae De Geer), flashed sheep (Bovicola ovis Schrank), the louse of cattle Korotkova blood-sucking (Haematopinus eurysternus Nitzsch), the louse of cattle blood-sucking red-breasted (Linognathus vituli Linnaeus) and other sucking lice and hematophagous biting parasites that attack people and animals; insect pests of the detachment Siphonoptera (fleas), including the rat flea (Xenopsylla cheopis Rotschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), flea chicken (Ceratophyllus gallinae Schrank), flea suction (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas, disturbing mammals and birds. Additional covered arthropods pests include spider squad, Agapee (spiders), such as the spider, the brown recluse (Loxosceles reclusa Gertsch &Mulaik) and spider-weaver black ("black widow") (Latrodectus mactans Fabricius), and Gubanova in the unit Scutigeromorpha (Scutigera), such as the Flycatcher common (Scutigera coleoptrata Linnaeus). The compounds of this invention are also active against the scholars of the classes Nematoda (Nematodes, Roundworms), Cestoda (cestodes, tapeworms), Trematoda (flukes) and Acanthocephala (skrebni), which includes economically important members of groups Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida, such as, but not limited to, an economically important agricultural pests (i.e. forming the root growths, root-knot nematodes in the genus Meloidogyne, damaging nematodes in the genus Pratylenchus, causing damage to the roots of nematodes in the genus Trichodoris, etc) and affect the health of man and animal pests (i.e., all economically important flukes, tapeworms and round worms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, At contortus in sheep, Dirofilaria immitis Leidy in dogs, At contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus in ruminants, etc)

The compounds of this invention find a particularly high activity against pests of Lepidoptera (butterflies) (e.g., Alabama agrillacea Hübner (Cutworm caterpillars of the cotton American), Archips argyrospila Walker (fruit tree leafrollers), A. rosana Linnaeus (caterpillars ermine moths) and other Archips species, Chilo suppressalis Walker (rice borers stem), Cnaphalocrosis medinalis Guenee (rice leafroller), Crambus caliginosellus Clemens (butterfly-the liquidation of the roots of corn), Crambus teterrellus Zincken (the liquidation matrichnoi), Cydia pomonella Linnaeus (Apple moth), Earias insulana Boisduval (prickly worm), Earias vitella Fabricius (scoops patnis is Oh), Helicoverpa armigera Hübner (scoops American), Helicoverpa zea Boddie (cotton Cutworm), Heliothis virescens Fabricius (tobacco Cutworm), Herpetogramma licarsisalis Walker (meadow moth), Lobesia botrana Denis & Schiffermüller (leafroller moth (grape), Pectinophora gossypiella Saunders (pink box of cotton worm), Phyllocnistis citrella Stainton (solecki citrus), Pieris brassicae Linnaeus (white cabbage), Pieris rapae Linnaeus (white small (rupnica)), Plutella xylostella Linnaeus (cabbage moth), Spodoptera exigua Hübner (marching worm beet), Spodoptera litura Fabricius (tobacco Cutworm, econopred, the larvae of which build a shared spider's nest), Spodoptera frugiperda J.E. Smith (scoops herbal), Trichoplusia ni Hübner (Cutworm cabbage, shovels) and Tuta absoluta Meyrick (flies tomato leaf miner)). The compounds of this invention are also commercially significant activity on members from the order Homoptera (ramnarine), comprising: Acyrthisiphon pisum Harris (pea aphid), Aphis craccivora Koch (alfalfa aphid), Aphis fabae Scopoli (bean aphid), Aphis gossypii Glover (cotton aphid, aphid bahcekoy), Aphis pomi De Geer (aphid Codling), Aphis spiraecola Patch (aphid tolkovoy), Aulacorthum solani Kaltenbach (aphid vonkova), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphus noxia Kurdjumov/MordviIko (wheat aphid Russian), Dysaphis plantaginea Paaserini (Apple aphid pink), Eriosoma lanigerum Hausmann (aphid Codling blood), Hyalopterus pruni Geoffroy (plum aphid opylene), Lipaphis erysimi Kaltenbach (aphid lookuphost), Metopolophium dirrhodum Walker (cereal aphid), Macrosipum euphorbiaeThomas (potato aphid leaf), Myzus persicae Sulzer (aphid peach-potato aphid green peach), Nasanovia ribisnigri Mosley (lettuce aphid). Pemphigus spp. (root aphids and gall aphid), Rhopalosiphum maidis Fitch (aphid corn leaf), Rhopalosiphum padi Linnaeus (bird-cherry aphid-osobuu), Schizaphis graminum Rondani (cereal aphid common), Sitobion avenae Fabricius (leaf aphid), Therioaphis maculata Buckton (aphid spotted alfalfa), Toxoptera aurantii Boyer de Fonscolombe (citrus aphid black) and Toxoptera citricida Kirkaldy (citrus aphid brown); Adelges spp. (Hermes, adelges); Phylloxera devastatrix Pergande (phylloxera Hickory), Bemisia tabaci Gennadius (the tobacco whitefly, sweet potato whitefly (sweet potatoes)), Bemisia argentifolii Bellows &Perring (whiteflies magnoliaceae), Dialeurodes citri Ashmead (citrus whitefly) and Trialeurodes vaporariorum Westwood (balakrishna greenhouse); Empoasca fabae Harris (cinadco potato), Laodelphax striatellus Fallen (cinadco small brown), Macrolestes quadrilineatus Forbes (cinadco Asteraceae), Nephotettix cinticeps Uhler (cinadco green), Nephotettix nigropictus Stal (cinadco rice), Nilaparvata lugens Stal (cinadco brown), Peregrinus maidis Ashmead (cinadco corn), Sogatella furcifera Horvath (cinadco short-tailed), Sogatodes orizicola Muir (delphacidae rice), Typhlocyba pomaria McAtee (cinadco Apple), Erythroneoura spp. (cycatki grape); Magicidada septendecim Linnaeus (cinadco 17-year-old); Icerya purchasi Maskell (mealybug Australian scaly), Quadraspidiotus perniciosus Comstock (the interior of California), Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (complex other bug); Cacopsylla pyricola Foerster (is Edenic pear), Trioza diospyri Ashmead (listblock horowuju). These compounds also exhibit activity on members from the order Hemiptera (Heteroptera (bugs)), including: Acrosternum hilare Say (green defender of rights), Anasa tristis De Geer (bug-robonica sad), Blissus leucopterus leucopterus Say (white-winged bug), Corythuca gossypii Fabricius (cotton bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich-Schäffer (Krasnikova cotton), Euchistus servus Say (bug-defender of rights brown), Euchistus variolarius Palisot de Beauvois (bug-defender of rights with one spot), Graptosthetus spp. (complex bugs-pests of seeds), Leptoglossus corculus Say (bug-crevice pine seeds), Lygus lineolaris Palisot de Beauvois (kapica meadow), Nezara viridula Linnaeus (bug cotton gardening), Oebalus pugnax Fabricius (rice bug), Oncopeltus fasciatus Dallas (bug Euphorbiaceae), Pseudatomoscelis seriatus Reuter (bug jumping cotton). Other insect orders, suppressed the compounds of this invention include the detachment of Thysanoptera (thrips) (for example, Frankliniella occidentalis Pergande (thrips Western), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips and Thrips tabaci Lindeman (onion thrips, thrips tobacco); and the order Coleoptera (beetles) (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (beetle Mexican bean) and larvae of click beetles of the genera Agriotes, Athous or Limonius).

The compounds of this invention can also be mixed with one or more other biological the ski active compounds or agents, including insecticides, fungicides, nematicides, bactericides, acaricides, growth regulators such as rooting stimulants, hemisternotomy, polychemical, repellents, attractants, pheromones, stimulants nutrition, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide, providing an even wider range of agricultural applicability. Thus, this invention relates also to a composition comprising a biologically effective amount of the compounds of formula 1 and an effective amount of at least one additional biologically active compound or agent, and the composition may additionally contain at least one surfactant, at least one solid diluent or a liquid diluent. Examples of such biologically active compounds or agents with which it can be prepared with the compounds of this invention are: insecticides such as abamectin, Arafat, acetamiprid, midflame (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, cigalotrin, lambda cigalotrin, qi is permethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, giovanola, emamectin, endosulfan, esfenvalerate, ethiprole, fanatical, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flucythrinate, Tau-fluvalinate, lufenuron (UR-50701), flufenoxuron, fonofos, halogenated, hexaflumuron, Imidacloprid, indoxacarb, isofenphos, lufenuron, Malathion, metaldehyde, metamidophos, methidathion, methomyl, methoprene, Methoxychlor, monocrotophos, methoxyfenozide, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathion-methyl, permethrin, Fort, fosalan, phosmet, phosphamidon, pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxifen, rotenon, spinosad, spiromesifen (BSN 2060), sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosulfat-sodium, tralomethrin, trichlorfon and triflumuron; fungicides, such as acibenzolar, AZOXYSTROBIN, benomyl, blasticidin-3, Bordeaux liquid (rejonowy copper sulphate), bromuconazole, cropropamide, captafol, Captan, carbendazim, chloroneb, CHLOROTHALONIL, copper oxychloride, copper salt, cyflufenamid, having cymoxanil, tsyprokonazolu, cyprodinil, (S) - for 3,5-dichloro-N-(3-chloro-1-ethyl 1-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281), diclocil (S-2900), declomycin, dicloran, difenoconazol, (S) - for 3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenyl is Ino)-4H-imidazol-4-one (RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, Dodin, edifenphos, epoxiconazol, famoxadone, fenamidone, fenarimol, fenbuconazole, paneramic (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, fentiazac, fistinginaction, fluazinam, fludyoksonil flamethower (RPA 403397), plumart/fluorin (SYP-L190), fluoxastrobin (CARRIED 5725), Fluconazol, flusilazol, flutolanil, flutriafol, folpet, fosetyl-aluminum, parallaxis, parameter (S-82658), hexaconazole, ipconazole, iprobenfos, iprodion, isoprothiolane, kasugamycin, kresoxim is methyl, MANCOZEB, MANEB, mefenoxam, mepronil, metalaxyl, metconazole, metamyosyn/phenominalrose (SSF-126), metrafenone (AS), myclobutanil, neo-atzin (metanational iron (III)), nicobifen (BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, provenzal, prochloraz, propamocarb, propiconazol, probenecid (DPX-KQ926), prothioconazole (JAU 6476), pirivenas, pyraclostrobin, Pyrimethanil, pyroxylin, jenoxifen, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazol, leflunomid, thiophanate-methyl, thiram, tadini, triadimefon, triadimenol, tricyclazole, Trifloxystrobin, triticonazole, validamycin and vinclozolin; nematicides, such as aldicarb, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides, such as amitraz, chinomethionat, Chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, Hairdryer who ahin, oxide fenbutatin, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, including subspecies aizawai and kurstaki Delta-endotoxin of Bacillus thuringiensis, baculovirus, and entomopathogenic bacteria, virus and fungi. The compounds of this invention and their compositions can be applied to plants genetically transformed to Express proteins toxic against invertebrate pests (such as Bacillus thuringiensis toxin). The effect of exogenously applied compounds of this invention inhibit invertebrate pests, can be synergistic with expressed protein toxins.

General reference regarding these agricultural protective agents is The Pesticide Manual, 12thEdition, C.D.S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2000.

Preferred insecticides and acaricides for mixing with compounds of this invention include pyrethroids such as cypermethrin, cigalotrin, cyfluthrin, beta-cyfluthrin, esfenvalerate, fenvalerate and tralomethrin; carbamates, such as fanatical, methomyl, oxamyl and thiodicarb; neonicotinoids such as clothianidin, Imidacloprid and thiacloprid; blockers of neuronal sodium channels, such as indoxacarb; insecticidal macrocyclic lactones such as spinosad, abamectin, avermectin emamectin; antagonists γ-aminobutyric acid (GABA), such as endosulfan, ethiprole and fipronil; urea insecticide, such as flufenoxuron and tifluadom; juvenile hormone mimetics, such as giovanola and pyriproxyfen; pymetrozine; and amitraz. Preferred biological agents for mixing with compounds of this invention include Bacillus thuringiensis Delta-endotoxin of Bacillus thuringiensis, as well as naturally occurring and genetically modified viral insecticides, including members of the family Baculoviridae, as well as insect-eating mushrooms.

The most preferred mixtures include a mixture of the compounds of this invention with cyhalothrin; a mixture of the compounds of this invention with beta-cyfluthrin; a mixture of the compounds of this invention with esfenvalerate; a mixture of the compounds of this invention with matomela; a mixture of the compounds of this invention with Imidacloprid; a mixture of the compounds of this invention with thiacloprid; a mixture of the compounds of this invention with indoxacarb; a mixture of the compounds of this invention with abamectin; a mixture of the compounds of this invention with endosulfan; a mixture of the compounds of this invention with ethiprole; a mixture of the compounds of this invention with fipronil; a mixture of the compounds of this invention with flufenoxuron; a mixture of the compounds of this invention with pyriproxyfen;the mixture the compounds of this invention with pymetrozine; a mixture of the compounds of this invention with nitraza; a mixture of the compounds of this invention with Bacillus thuringiensis and a mixture of the compounds of this invention with the Delta-endotoxin of Bacillus thuringiensis.

In some cases, to overcome the resistance of pests especially preferred are combinations with other compounds for combating invertebrate pests. Thus, the composition according to the invention may further comprise a biologically effective amount of at least one additional compound or agent for combating invertebrate pests, which have a similar range kill pests, but different mechanism of action. The contacting of plants genetically modified for expression protects plant compounds (e.g., protein), or the locus of the plant with a biologically effective amount of the compounds of this invention can also provide a wider range of plant protection and can be useful for overcoming resistance to pests.

The quantitative relationships using such compounds or agents together with the compound described by formula 1, are determined by the norms of the latter, a well-known professionals from publicly available information sources, in particular the above-mentioned reference source (1)"The Pesticide Manual", and other General reference manuals (detailed output cited reference guides below after table 4).

The following table 4 includes data standards for the application of known biologically active compounds or agents in accordance with the specified publicly available sources of information and the calculated mass ratios for the use of such compounds or agents together with the compound described by formula 1. Table 4 presents the name of the known biologically active compound or agent (column 1), the class to which it belongs according to its pesticide action (column 2), the application rate in grams per hectare (g/ha) for known biologically active compound or agent (column 3), the reference to a known reference source from which you obtained the application rate (column 4) and mathematically derived the ratio by weight between the compound described by formula 1, and known biologically active compound or agent (column 5).

For example, the second line in table 4 shows that abamectin is a macrocyclic lactone is characterized by the rate 5-28 g/ha This information is available in the reference source 1 - "The Pesticide Manual". The mass ratio between the compound described by formula 1, and abamectin is the kind of band ranging from 400:1 to 1:2,8. The first ratio of 400:1 is obtained dividing the highest standards for the compounds described by formula 1 (2000 g/ha), the lowest rate for abamectin (5 g/ha). Similarly, the division of the highest standards for abamectin (28 g/ha) at the lowest rate for the compounds described by formula 1, (10 g/ha) results in a ratio of 1:2,8. Mass ratios listed in table 4 for other known biologically active compounds or agents, calculated in the same way.

TABLE 4

1500-5000
Additional biologically active ingredientClass biologically active componentThe application rate (g/ha)Reference sourcePossible mass ratio
The compound described by formula 1 (main biologically active component)10-2000The present invention
The abamectinMacrocyclic lactones5-281From 400:1 to 1:2,8
ArafatOrganophosphorus compound500-10001From 4:1 to 1:100
AcetamipridThe neonicotinoids20-1001From 100:1 to 1:10
AvermectinMacrocyclic lactones5-401From 400:1 to 1:4
Azadirachtin10-202From 200:1 to 1:2
Amitraz300-10002From 7:1 to 1:100
BifenthrinPyrethroids5-451From 400:1 to 1:4,5
Bifenazate250-7501From 8:1 to 1:75
Buprofezin50-5001From 40:1 to 1:50
The carbofuranCarbamates300-34002From 7:1 to 1:340
Chlorfenapyr50-1002From 40:1 to 1:10
Chlorfluazuron12-1002From 167:1 to 1:10
The chlorpyrifosOrganophosphorus compound110-57002From 18:1 to 1:570
ChlorpyrifosOrganophosphorus compound2From 1:1 to 1:500
Chromafenozide25-502From 80:1 to 1:5
ClothianidinThe neonicotinoids502From 40:1 to 1: 5
CyfluthrinPyrethroids15-401133:1 to 1:4
Beta-cyfluthrinPyrethroids7,5-201From 267:1 to 1:2
CigalotrinPyrethroids5-302From 400:1 to 1:3
Lambda cigalotrinPyrethroids5-302From 400:1 to 1:3
CypermethrinPyrethroids23-85287:1 to 1:8,5

Additional biologically active ingredientClass biologically active componentThe application rate (g/ha)Reference sourcePossible mass ratio
Cyromazine75-4501From 27:1 to 1:45
DeltamethrinPyrethroids2.5 to 1 1From 800:1 to 1:2,1
Diafenthiuron300-5001From 7:1 to 1:50
DiazinonOrganophosphorus compound300-6001From 7:1 to 1:60
Diflubenzuron25-1501From 80:1 to 1:15
TimeoutOrganophosphorus compound300-7002From 7:1 to 1:70
Giovanola10-152From 200:1 to 1:1,5
Emamectin (benzoate)5-251From 400:1 to 1:2,5
Endosulfan30-602From 67:1 to 1: 6
Amiprol300-4502From 7:1 to 1:45
EsfenvaleratePyrethroids5-251From 400:1 to 1:2,5
FanaticalCarbamates1200-18001From 2:1 to 1:180
FenoxycarbSimulators juvenile hormone1130-17002From 2:1 to 1:17
FenpropathrinPyrethroids1142From 18:1 to 1:11,4
FenvaleratePyrethroids55-2272From 36:1 to 1:22,7
FipronilAntagonist of GABA10-2001From 200:1 to 1:20
Flonicamid50-1002From 40:1 to 1:10
FlucythrinatePyrethroids25-502From 80:1 to 1:5
Tau-flucythrinatePyrethroids28-1142From 71:1 to 1:11,4
Flutterin10-552From 200:1 to 1:5,5
Flufenoksuron5-1002From 400:1 to 1:10
Fonofos1000-15002From 2:1 to 1:150
Halogenated1120-22401From 2:1 to 1:224
HexaflumuronUrea70-2802From 29:1

Additional biological the automatic active ingredient Class biologically active componentThe application rate (g/ha)Reference sourcePossible mass ratio
insecticidal action1:28
ImidaclopridThe neonicotinoids35-490257:1 to 1:49
IndoxacarbBlockers of neuronal sodium channelsa 12.5-1251From 160:1 to 1:12,5
IsofenphosOrganophosphorus compound1120-22403From 2:1 to 1:224
LufenuronUrea insecticidal action10-501From 200:1 to 1:5
Malathion600-34002From 3:1 to 1:340
MethamidophosOrganophosphorus compound350-12001From 6:1 to 1:120
MitigationOrganophosphorus compound300-23002From 7:1 to 1:230
MethomylCarbamates110-17002From 18:1 to 1:170
MethopreneSimulators juvenile hormone57-1142From 35:1 to 1:11,4
Methoxychlor280-5602From 7:1 to 1:56
MonocrotophosOrganophosphorus compound250-5002From 8:1 to 1:50
Methoxyfenozide20-3001From 100:1 to 1:30
NovaluronUrea insecticidal action75-2502From 27:1 to 1:25
OxamylCarbamates3002From 7:1 to 1:30
ParathionOrganophosphorus compound113-11302From 18:1 to 1:113
ParathionmethylOrganophosphorus compound113-11302From 18:1 to 1:113
PermethrinPyrethroids25-2001From 80:1 to 1:20
PortOrganophosphorus compound750-34001From 3:1 to 1:340
FozalonOrganophosphorus compound 500-15002From 4:1 to 1:150
PhosmetOrganophosphorus compound500-10001From 4:1 to 1:100
Phosphamidon300-17002From 7:1 to 1:170

Additional biologically active ingredientClass biologically active componentThe application rate (g/ha)Reference sourcePossible mass ratio
PirimicarbCarbamates50-7501From 40:1 to 1:75
ProfenofosOrganophosphorus compound600-12001From 3:1 to 1:120
Pymetrozine150-3001From 13:1 to 1:30
Pyridaben100-3001From 20:1 to 1:30
Pyridalyl84-2242From 24:1 to 1:22,4
PyriproxifenSimulator juvenile hormone25-1252From 80:1 to 1:12,5
Rotenon600-23002From 3:1 to 1:230
SpinosadMacrocyclic lactones25-1502From 80:1 to 1:15
Spiromesifen400-7501From 5:1 to 1:75
SulprofosOrganophosphorus compound600-17002From 3:1 to 1:170
Tebufenozide66-3351From 30:1 to 1:33,5
TeflubenzuronUrea insecticidal action20-2002From 100:1 to 1:20
TefluthrinPyrethroids12-1502From 167:1 to 1:15
TerbufosOrganophosphorus compound250-20001From 8:1 to 1:200
TetrachlorvinphosOrganophosphorus compound110-17002From 18:1 to 1:170
ThiaclopridThe neonicotinoids48-2162From 42:1 to 1:21,6
ThiamethoxamThe neonicotinoids10-2001From 200:1 to 1:20
ThiodicarbCarbamates200-10001From 10:1 to 1:100
TralomethrinPyrethroids7,5-201From 267:1 to 1:2
TrichlorfonOrganophosphorus compound300-12001From 7:1 to 1:120
Triflumuron57-5672From 35:1 to 1:57
AldicarbCarbamates600-114002From 3:1 to 1:1140
Chinomethionat415-11222From 5:1 to 1:112

Additional biologically active ingredientClass biologically active componentThe application rate (g/ha)Reference sourcePossible mass ratio
Cyhexatin20-302From 100:1 to 1:3
Dicofol500-20001From 4:1 to 1:200
Dienochlor110-2203From 18:1 to 1:22
Etoxazole50-1001From 40:1 to 1:10
Finishin56-5602From 36:1 to 1:56
Oxide fenbutatin600-23002From 3:1 to 1:230
Fenpyroximate25-502From 80:1 to 1:5
Hexythiazox150-3001From 13:1 to 1:30
Propargite750-18001From 3:1 to 1:180
Tebufenpyrad50-2001From 40:1 to 1:20
The Delta-endotoxin of Bacillus thuringiensis560-22402From 4:1 to 1:224
Bacillus thuringiensis, subspecies kurstaki90-5002From 22:1 to 1:50

(1) The Pesticide Manual, 12thEdition, C.D.S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, UK., 2000.

(2) Global Insecticide Directory, 2nd Edition, R.Bryant, M.G.Bite and W.L.Hopkins, Ed., Agranova, Orpington, Kent, UK., 1999.

(3) Insect and Disease Control Guide, Vol. 1, R..Meister Ed., Meister Publishing Company, Willoughby, OH, USA, 1999.

EXAMPLE F

Table E lists the specific composition containing a compound described by formula 1, together with other biologically active components, designed to suppress the development of invertebrate pests in accordance with the methods of the present invention. Rooms compounds listed in the first column of the table E, correspond to the numbers of the compounds given in TABLE INDEXES A.

In the second column of table E lists the specific additional biologically active components (for example, "abamectin" in the first line). In the third column of table E shows the class belongs to a particular connection. In the fourth column of table E shows the typical range of mass ratios for quantities, using an additional component in relation to the compound described by formula 1, for example, From 50:1 to 1:10" abamectin against the connection 1 in the calculation of the mass). Thus, the first row of the table, i.e., specifically describes the combination of the compounds described by formula 1, compounds 1 and abamectin, and it specifies that abamectin is representative of the macrocyclic lactones, and it is reported that abamectin and connection 1 is usually used in a mass ratio in the range from 50:1 to 1:10. The information in the rest of the rows in the table E should be interpreted in the same way.

Table E

A composition comprising a compound described by formula 1, and at least one additional biologically active compound or agent.

The connection numberAdditional biologically active ingredientClassConventional mass ratio
1The abamectinMacrocyclic lactoneFrom 50:1 to 1:10
2ArafatOrganophosphateFrom 100:1 to 1:100
3AcetamipridThe neonicotinoidFrom 150:1 to 1:200
4AldicarbCarbamateFrom 200:1 to 1:100
5MidflameFrom 200:1 to 1:100
7AmitrazFormamidineFrom 200:1 to 1:100
8AvermectinMacrocyclic lactoneFrom 50:1 to 1:10
9AzadirachtinPlant extractsFrom 100:1 to 1:100
11AzinphosmethylOrganophosphateFrom 100:1 to 1:100
12The Delta-endotoxin of Bacillus thuringiensisBiological agentFrom 50:1 to 1:10
13Bacillus thuringiensis, subspecies AizawaiBiological the cue agent of the From 50:1 to 1:10
14Bacillus thuringiensis, subspecies KurstakiBiological agentFrom 50:1 to 1:10
15BaculovirusBiological agentFrom 50:1 to 1:10
16Beta-cyfluthrinPYRETHROIDFrom 50:1 to 1:20
17BifenazateFrom 200:1 to 1:100
18BifenthrinPYRETHROIDFrom 50:1 to 1:10
19BuprofezinInhibitor of chitin synthesisFrom 10:1 to 1:150
21The carbofuranThe carbofuranFrom 200:1 to 1:100
22ChinomethionatCinoxacinFrom 200:1 to 1:100

td align="center"> Bridge diphenyl
The connection numberAdditional biologically active ingredientClassConventional mass ratio
23ChlorfenapyrThe arylpyrol1200:1 to 1:200
24ChlorfluazuronInhibitor of chitin synthesisFrom 10:1 to 1:150
25Chlorbenzyl the t Bridge diphenylFrom 50:1 to 1:50
26The chlorpyrifosOrganophosphateFrom 100:1 to 1:100
27ChlorpyrifosOrganophosphateFrom 100:1 to 1:100
28ChromafenozideThe molting hormone agonistFrom 50:1 to 1:250
29ClothianidinThe neonicotinoidFrom 100:1 to 1:400
31CyfluthrinPYRETHROIDFrom 50:1 to 1:10
32CigalotrinPYRETHROIDFrom 50:1 to 1:10
33CyhexatinOlaverganiFrom 100:1 to 1:100
34CypermethrinPYRETHROIDFrom 50:1 to 1:10
35CyromazineInhibitor of chitin synthesisFrom 10:1 to 1:150
36DeltamethrinPYRETHROIDFrom 50:1 to 1:10
37DiafenthiuronThioureaFrom 150:1 to 1:200
38DiazinonOrganophosphateFrom 100:1 to 1:100
39DicofolFrom 200:1 to 1:100
41DienochlorChlororganicFrom 100:1 to 1:100
42DiflubenzuronInhibitor of chitin synthesisFrom 10:1 to 1:150
43TimeoutOrganophosphateFrom 100:1 to 1:100
44GiovanolaThe molting inhibitorFrom 100:1

The connection numberAdditional biologically active ingredientClassConventional mass ratio
up to 1:100
45EmamectinMacrocyclic lactoneFrom 50:1 to 1:10
46EndosulfanAntagonist of GABAFrom 50:1 to 1:100
47Entomopathogenic bacteriumBiological agentFrom 50:1 to 1:50
48Entomopathogenic virusBiological agentFrom 50:1 to 1:50
49Insect-eating fungusBiological agentFrom 50:1 to 150
51EsfenvaleratePYRETHROIDFrom 100:1 to 1:10
52AmiprolAntagonist of GABAFrom 50:1 to 1:100
. 53EtoxazoleInhibitor development mitesFrom 50:1 to 1:50
54FenamiphosOrganophosphateFrom 100:1 to 1:100
55FinishinInhibitor of mitochondrial transport of electronsFrom 200:1 to 1:100
56Oxide fenbutatinOlaverganiFrom 100:1 to 1:100
57FanaticalCarbamateFrom 200:1 to 1:100
58FenoxycarbSimulator juvenile hormoneFrom 200:1 to 1:100
59FenpropathrinPYRETHROIDFrom 100:1 to 1:10
61FenpyroximateInhibitor of mitochondrial transport of electronsFrom 200:1 to 1:100
62FenvaleratePYRETHROIDFrom 100:1 to 1:10
63FipronilAntagonist of GABAFrom 50:1 to 1:100
64FlonicamidThe neonicotinoidFrom 200:1 to 1:100

The connection numberAdditional biologically active ingredientClassConventional mass ratio
65FlucythrinatePYRETHROIDFrom 50:1 to 1:10
66FlutterinPyrimidinamineFrom 200:1 to 1:100
67FlufenoksuronUrea insecticidal actionFrom 10:1 to 1:150
68FonofosOrganophosphateFrom 100:1 to 1:100
69HalogenatedThe molting hormone agonistFrom 50:1 to 1:250
71HexaflumuronUrea insecticidal actionFrom 10:1 to 1:150
72HexythiazoxInhibitor development mitesFrom 50:1 to 1:50
73ImidaclopridThe neonicotinoidFrom 100:1 to 1:200
74IndoxacarbBlocker of neuronal sodium channelsFrom 100:1 to 1:200
75 IsofenphosOrganophosphateFrom 100:1 to 1:100
76Lambda cigalotrinPYRETHROIDFrom 50:1 to 1:10
77LufenuronUrea insecticidal actionFrom 10:1 to 1:150
78MalathionOrganophosphateFrom 100:1 to 1:100
79MetaldehydeFrom 200:1 to 1:100
81MethamidophosOrganophosphateFrom 100:1 to 1:100
82MitigationOrganophosphateFrom 100:1 to 1:100
83MethomylCarbamateFrom 200:1 to 1:100
84MethopreneSimulator juvenile hormoneFrom 200:1 to 1:100

The connection numberAdditional biologically active ingredientClassConventional mass ratio
85MethoxychlorChlororganicFrom 100:1 to 1:100
86MethoxyfenozideThe molting hormone agonist50:1 is about 1:250
87MonocrotophosOrganophosphateFrom 100:1 to 1:100
88NetizenThe neonicotinoidFrom 150:1 to 1:200
89NovaluronUrea insecticidal actionFrom 10:1 to 1:150
91NoviflumuronInhibitor of chitin synthesisFrom 10:1 to 1:150
92OxamylCarbamateFrom 100:1 to 1:50
93ParathionOrganophosphateFrom 100:1 to 1:100
94ParathionmethylOrganophosphateFrom 100:1 to 1:100
95PermethrinPYRETHROIDFrom 100:1 to 1:10
96PortOrganophosphateFrom 100:1 to 1:100
97FozalonOrganophosphateFrom 100:1 to 1:100
98PhosmetOrganophosphateFrom 100:1 to 1:100
99PhosphamidonOrganophosphateFrom 100:1 to 1:100
101PirimicarbCarbamateFrom 200:1 to 1:100
102ProfenofosOrganophosphateFrom 100:1 to 1:100
103PropargiteEster of sulphurous acidFrom 100:1 to 1:200
104PymetrozineAntifeedingFrom 200:1 to 1:100
105PyridabenInhibitor of mitochondrialFrom 200:1 to 1:100

The connection numberAdditional biologically active ingredientClassConventional mass ratio
transport of electrons
106PyridalylFrom 200:1 to 1:100
107PyriproxifenSimulator juvenile hormoneFrom 200:1 to 1:100
108RotenonInhibitor of mitochondrial transport of electronsFrom 200:1 to 1:100
109SpinosadMacrocyclic lactoneFrom 50:1 to 1:10
111SpiromesifenTeranova acidFrom 100:1 to 1:200
112 SulprofosOrganophosphateFrom 100:1 to 1:100
113Tau-fluvalinatePYRETHROIDFrom 100:1 to 1:10
114TebufenozideThe molting hormone agonistFrom 50:1 to 1:250
115TebufenpyradInhibitor of mitochondrial transport of electronsFrom 200:1 to 1:100
116TeflubenzuronInhibitor of chitin synthesisFrom 10:1 to 1:150
117TefluthrinPYRETHROIDFrom 100:1 to 1:10
119TerbufosOrganophosphateFrom 100:1 to 1:100
121TetrachlorvinphosOrganophosphateFrom 100:1 to 1:100
122ThiaclopridThe neonicotinoidFrom 100:1 to 1:200
123ThiamethoxamThe neonicotinoidFrom 100:1 to 1:200
124ThiodicarbCarbamatesFrom 200:1 to 1:100
125Thiosulfat-sodiumOxycarbonateFrom 200:1 to 1:100
126TralomethrinPyrethroids From 100:1 to 1:10

The connection numberAdditional biologically active ingredientClassConventional mass ratio
127TrichlorfonOrganophosphateFrom 100:1 to 1:100
128TriflumuronUrea insecticidal actionFrom 10:1 to 1:150

Mixtures containing combinations of active ingredients listed in table E, with mass ratios 1:1, was using a solution containing 10% acetone, 90% water and 300 hours/million non-ionic surfactant X-77® Spreader Lo-Foam Formula, containing alkalinisation, free fatty acids, glycols and isopropanol, (from Loveland Industries, Inc.), and tested in accordance with the Protocol described for TESTING AND where the concentration of each active component was 50 hours/million Each of the mixtures was achieved excellent levels of plant protection (10% or less damage due to eating).

Invertebrate pests are destroyed when agricultural and non-agricultural uses through the application of one or more compounds of this invention in an effective amount is ve on the environment of these pests, including agricultural and/or non-agricultural center of pest infestation, to be protected zone or directly on the subject to pest control. Thus, the invention additionally relates to a method of combating invertebrate pests, involving contacting the invertebrate pest or their environment with a biologically effective amount of one or more compounds of this invention or a composition containing at least one such compound, or composition comprising at least one such compound and an effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions containing the compound of this invention and an effective amount of at least one additional biologically active compound or agent, include granular compositions, in which the additional biologically active compound or agent is present on the same pellet as the connection of the present invention, or granules that are present separately from the granules of the compounds of this invention.

Preferred method of contact is by spraying. Alternatively, the granulated composition comprising a connection of the giving of this invention, can be applied to the foliage of plants or to the soil. The compounds of this invention effectively delivered through the absorption plant by contacting the plant with a composition comprising a compound of this invention used in the form of impregnation of the soil liquid ready-made form, depositing a granular form into the soil, processing mailbox for Sarantsev or dipping of seedlings. The compounds are also effective when topically applying the composition containing the compound of the present invention, the focus of pest infestation. Other methods of contact include the application of the compounds or compositions of the present invention using solutions for contact spraying of direct action or solutions with aftereffect, air solutions, sprays, gels, drazhirovanija seeds (coating on the seeds), microencapsulation, systemic absorption, lures, clips, boles, romanobritish, fumihito, aerosols, Farrukh Dustov and many other tools. The compounds of this invention can also be impregnated materials for the manufacture of devices for combating invertebrate pests (e.g., nets for insects).

The compounds of this invention can be incorporated into baits, which are eaten by invertebrates, or can find what I'm in such devices, as traps, etc. Granules or baits containing 0.01 to 5% of the active ingredient, 0.05 to 10% moisture retaining agent (agents) and 40-99% vegetable flour, are effective in the destruction of soil insects at very low application rates, particularly at doses of active ingredient, which are fatal if swallowed and not by direct contact.

The compounds of this invention may be applied in pure form, but is most often used in finished form, containing one or more compounds with suitable carriers, diluents and surfactants and possibly in combination with food, depending on the intended end use. The preferred method of application involves spraying water dispersion or solution in refined oil of these compounds. Combination with spray oils, the concentration razbryzgivanii oils that increase the stickiness agents for spreaders, adjuvants, other solvents and synergists, such as piperonylbutoxide, often increase the efficiency of the connection.

The rate of application required for effective suppression (i.e. the "biologically effective amount")will depend on such factors as type bespozvonochnykh, subject to destruction, the life cycle of the pest, life stage, its size, place ulozhenie, the time of year, culture or animal host, "feeding behavior, mating behavior, humidity, ambient temperature, etc. Under normal circumstances, the norms of application of about 0.01 to 2 kg of active ingredient per hectare are sufficient to control pests in agricultural and ecological systems, but may be sufficient for such a small amount as of 0.0001 kg/ha, or may require such a large number as 8 kg/ha. For non-agricultural applications of effective rates of application will be in the range of from about 0.1 to 50 mg/square meter, but may be sufficient for such a small amount as 0.1 mg/square meter, or may require such a large number as 150 mg/square meter. The person skilled in the art can easily determine the biologically effective amount necessary for the desired level of suppression bespozvonochnykh pest.

The following Tests under Biological examples of the invention demonstrate the effectiveness of suppression compounds of this invention on specific pests. "The effectiveness of suppression is the inhibition of the development of arthropods (including mortality), which causes significantly reduced eating. However, protection from pests, done by the implemented these compounds, not limited to these species. Cm. The table Indexes And descriptions of the connections. In this index table uses the following abbreviations: t means tertiary, n means normal, i means ISO, s means secondary. Me means methyl, Et means ethyl, Pr means propyl and Bu means butyl; accordingly, i-Pr means isopropyl, sBu means of secondary butyl, etc. Abbreviation "Ex" means "Example" and is accompanied by a number that indicates whether the sample obtained this connection.

TABLE INDEXES
ConnectionR1R2R3R4AR4bR5TPL (°C)
1MeBrCF3i-PrHCl197-198
2 (App.1)MeClCF3i-PrHCl195-196
3MeClCF3t-BuHCl223-225
4 (PR)Me ClCF3MeHCl185-186
5BrBrCF3i-PrHCl192-193
6BrBrCF3t-BuHCl246-247
7BrBrCF3MeHCl162-163
8BrBrCF3EtHCl188-189
9ClClCF3i-PrHCl200-201
10ClClCF3t-BuHCl170-172
11ClClCF3MeHCl155-157
12ClClCF3EtHCl201-202
13MeBrCF3t-BuH Cl247-248
14MeBrCF3EtHCl192-193
15MeFCF3i-PrHCl179-180
16MeBrBri-PrHCl185-187
17MeCF3CF3i-PrHCl235-236
18MeCF3CF3EtHCl216-217
19MeICF3i-PrHCl188-189
20 (PR)MeClBrMeHCl162-164
21MeClBrt-BuHCl159-161
22BrBrBri-PrHCl162-163
23BrBr BrMeHCl166-168
24BrBrBrt-BuHCl210-212
25ClClBri-PrHCl188-190

41
ConnectionR1R2R3R4aR4bR5TPL (°C)
26ClClBrt-BuHCl179-180
27 (PR)MeClBri-PrHCl159-161
28ClClCF3i-PrHCl200-202
29ClBrCF3t-BuHCl143-145
30ClBrCF3MeHCl171-173
31Me BrBrMeHCl147-149
32MeBrCF3MeHCl222-223
33 (PR)MeClCli-PrHCl173-175
34 (PR)MeClClMeHCl225-226
35MeClClt-BuHCl163-165
36MeBrCli-PrHCl152-153
37MeBrClMeHCl140-141
38MeBrBrt-BuHCl215-221
39MeICF3MeHCl199-200
40MeCF3CF3t-BuHCl148-149
MeClClEtHCl199-200
42BrBrCli-PrHCl197-199
43BrBrClMeHCl188-190
44BrBrClt-BuHCl194-196
45BrBrClEtHCl192-194
46ClClCli-PrHCl197-199
47ClClClMeHCl205-206
48ClClClt-BuHCl172-173
49ClClClEtHCl206-208
50MeFBrt-BuHCl124-125
5 BrBrBrEtHCl196-197
52ClClBrMeHCl245-246
53ClClBrEtHCl214-215
54MeBrBrEtHCl194-196
55MeIBrMeHCl229-230
56MeIBri-PrHCl191-192
57MeCF3CF3MeHCl249-250
58MeClCF3EtHCl163-164
59MeICF3EtHCl199-200
60MeICF3t-BuHCl 242-243
61MeClBrEtHCl194-195

ConnectionR1R2R3R4aR4bR5TPL (°C)
62MeFCF3MeHCl213-214
63MeFCF3EtHCl212-213
64MeFCF3t-BuHCl142-143
65MeFBrMeHCl214-215
66MeFBrEtHCl205-205
67MeFBri-PrHCl206-208
68MeFCli-PrHCl14-185
69MeFClMeHCl180-182
70MeFClEtHCl163-165
71MeBrClEtHCl192-194
72MeIClMeHCl233-234
73MeIClEtHCl196-197
74MeICli-PrHCl189-190
75MeIClt-BuHCl228-229
76MeBrClt-BuHCl224-225
77BrBrClMeMeCl153 to 155
78MeBrCF3MeMeCl207-20
79ClClClMeMeCl231-232
80BrBrBrMeMeCl189-190
81ClClBrMeMeCl216-218
82ClClCF3MeMeCl225-227
83MeBrOch2CF3i-PrHCl213-215
84MeBrOch2CF3MeHCl206-208
85MeClOch2CF3i-PrHCl217-218
86MeClOch2CF3EtHCl205-207
87 (PR)MeClOch2CF3MeHCl207-208
88 MeBrOch2CF3EtHCl208-211
89MeBrOch2CF3t-BuHCl213-216
90BrBrCF3MeMeCl228-229
91ClBrCF3MeMeCl238-239
92ClOch2CF3i-PrHCl232-235
93ClClOch2CF3MeHCl192-195 (in Russian)
94ClClOch2CF3MeMeCl132-135
95BrBrOch2CF3i-PrHCl225-227
96BrBrOch2CF3MeHCl206-208
97/td> BrBrOch2CF3MeMeCl175-177

105
ConnectionR1R2R3R4aR4bR5TPL (°C)
98ClBrBrMeMeCl237-238
99ClBrClMeHCl228-229
100ClBrClMeMeCl236-237
101ClBrBrMeHCl226-227 of
102ClFCF3MeMeCl215-216
103ClFCF3MeHCl219-220
104BrFBrMeMeCl235-236
BrFBrMeHCl238-239
106BrFBri-PrHCl236-237
107BrFClMeMeCl246-247
108BrFClMeHCl233-234
109BrFCli-PrHCl153-154
110MeFClMeMeCl242-243
111ClFBrMeMeCl245-246
112ClFBrMeHCl217-218
113ClFBri-PrHCl168-169
114ClFClMeMeCl239-240
15 ClFClMeHCl248-249
116ClFCli-PrHCl169-170
117BrFCF3MeMeCl191-192
118BrFCF3MeHCl228-229
119BrFCF3i-PrHCl224-226
120BrClBrMeMeCl188-189
121BrClBrMeHCl248-249
122BrClBri-PrHCl252-253
123BrClClMeMeCl147-148
124BrClClMeHCl249-25
125BrClCli-PrHCl239-240
126BrClCF3MeMeCl200-201
127BrClCF3MeHCl158-159
128BrClCF3i-PrHCl250-250
129MeClClMeMeCl232-233
130MeClBrMeMeCl210-211
131FFBrMeHCl197-198
132FFBrMeMeCl218-222
133FClBrMeHCl203-204

Connection R1R2R3R4aR4bR5TPL (°C)
134FClBrMeMeCl226-227 of
135FClBri-PrHCl207-208
136FClClMeHCl211-212
137FClClMeMeCl237-238
138FFClMe Cl159-160
139FFClMeMeCl225-226
140FFCli-PrHCl201-202
141FBrBrMeHCl209-210
142FBrBrMeMeCl225-226
143FBrBri-PrHCl208-209
144FBrCl/td> MeHCl209-210
145FBrClMeMeCl244-245
146FBrCli-PrHCl207-208
147FBrOch2CF3MeHCl210-211
148FBrOch2CF3MeMeCl204-206
TABLE INDEXES
ConnectionR1R2R3 R4aR4bR5Melting point (°)
149ClClBrISO-PrHCl224-226

TABLE INDEXES
ConnectionR1R2R3R5Melting point (°)
150MeBrCF3Cl*
151MeClCF3Cl*
152MeClCF3Cl*
153MeClBrCl*
154MeClClCl*
155MeCl Och2CF3Cl*
156BrBrBrCl*
157ClClClCl*
158MeBrBrCl207-210
159MeCF3CF3Cl*
160FClBrCl*
* Data1H NMR are presented in table indexes D.

BIOLOGICAL EXAMPLES of the INVENTION

TEST AND

To assess the destruction of the cabbage moth (Plutella xylostella) the testing device consisted of a small open container, inside of which were 12-14-day plants of radish. It was previously infected 10-15 newborn caterpillars on a piece of a diet of insects using a sampler with an internal cavity (rod) for the fence "tube" from the layer of hardened diet of insects, on which grow numerous caterpillars, and transfer of the sample-the"tube"containing larvae and diet, in the device for testing.

Compound (t is St-compounds) were prepared using solution, containing 10% acetone, 90% water and 300 hours per million of a mixture of nonionic surfactant X-77® Spreader Lo-Foam containing alkalinisation, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.), if there are no other indications. The prepared compounds were applied in 1 ml of liquid through the tip for atomized spray SUJ2 with custom enclosure 1/8 JJ (Spraying Systems Co.), placed at a distance of 1.27 cm (0.5 inch) above the upper part of each device for testing. All experimental compounds in this screening was sprayed at the rate of 50 ppm, and tested in three replicates. After spraying the prepared test the connection to each device for testing was allowed to dry for 1 hour and then it was placed on top of black mesh cover. These test devices was kept for 6 days in the chamber for growing at 25°C and 70% relative humidity. Then visually assessed the damage caused by eating plants.

Of the tested compounds, the following compounds were provided excellent levels of plant protection (10% or less damage as a result of eating): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137.

TEST

To assess the destruction scoops herbal (Spodoptera frugiperda), the testing device consisted of a small open container with a 4-5-day maize plants inside of it, pre-infected 10-15 day caterpillars on a piece of a diet of insects using a sampler with an internal rod, as described in test A.

Compound (test compound) was prepared and sprayed at the rate of 50 hours/million, as described for test A. Spraying was performed three times (in three replicates). After spraying appliances for testing was kept in the chamber for growing and then visually evaluated as described for test A.

Of the tested compounds, the following compounds were provided excellent levels of plant protection (10% or less damage as a result of eating): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137.

TEST

To assess the destruction of the tobacco Cutworm (Heliothis virescens) of the mouth of austo for testing consisted of a small open container with a 6-7-day plants of cotton inside, pre-infected 8 two-day tracks on a piece of a diet of insects using a sampler with an internal rod, as described for test A.

Compound (test compound) was prepared and sprayed at the rate of 50 hours/million, as described for test A. Spraying was performed three times (in three replicates). After spraying appliances for testing was kept in the chamber for growing and then visually evaluated as described for test A.

Of the tested compounds, the following compounds were provided excellent levels of plant protection (10% or less damage as a result of eating): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129.

TEST D

To assess the destruction of small scoops (Spodoptera exigua), the testing device consisted of a small open container with a 4-5-day maize plants inside of it, pre-infected 10-15 day caterpillars on a piece of a diet of insects using a sampler with an internal rod, as described for test A.

Compound (test compound) goth is wheelie and was sprayed at the rate of 50 hours/million as described for test A. Spraying was performed three times (in three replicates). After spraying appliances for testing was kept in the chamber for growing and then visually evaluated as described for test A.

Of the tested compounds, the following compounds were provided excellent levels of plant protection (10% or less damage as a result of eating): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 100 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129.

TEST E

To assess the destruction aphid green peach (Myzus persicae) through contact and/or system, the testing device consisted of a small open container with 12-15-day plant radishes inside previously infected location on the sheet of the test plants 30-40 insects on a piece of sheet cut from cultivated plants (way cut sheet). Caterpillars moved on the tested plants as dehydration of the piece of sheet. After a preliminary soil contamination device for testing covered with a layer of sand.

Compound (test compound) were prepared using the-W solution containing 10% acetone, 90% water and 300 hours per million of a mixture of nonionic surfactant X-77® Spreader Lo-Foam containing alkalinisation, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.), if there are no other indications. The prepared compounds were applied in 1 ml of liquid through the tip for atomized spray SUJ2 with custom enclosure 1/8 JJ (Spraying Systems Co.), placed at a distance of 1.27 cm (0.5 inch) above the upper part of each device for testing. All experimental compounds in this screening were sprayed at 250 ppm, and tested in three replicates. After spraying the prepared test the connection to each device for testing was allowed to dry for 1 hour and then it was placed on top of black mesh cover. These test devices was kept for 6 days in the chamber for growing at 19-21°C and 50-70% relative humidity. Then each device for testing were visually evaluated on the mortality of insects.

Of the tested compounds, the following compounds gave at least 80% mortality: 1, 2, 3,4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 16, 20, 21, 22, 23, 25, 26, 27, 28, 29, 31, 32, 33, 36, 38, 39, 41, 42, 43, 45, 46, 47, 49, 51, 52, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 69, 72, 74, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 90, 91, 93, 98, 99, 100, 101, 102, 103, 104, 105, 106, 108, 109, 111, 112, 113, 114, 115, 116, 126, 127, 128, 131, 135.

TEST F

To estimate the d is the supply of cotton aphid (aphid melon) (Aphis gossypii) through contact and/or system, the testing device consisted of a small open container with a 6-7-day plants of cotton inside, pre-infected 30-40 insects on a piece of sheet in accordance with the method of cut sheet described for test E, and the ground device for testing covered with a layer of sand.

Compound (test compound) was prepared and sprayed at the rate of 250 hours/million, as described for test A. Spraying was tested in three replicates. After spraying appliances for testing was kept in the chamber for growing and then visually evaluated as described for test E.

Of the tested compounds, the following compounds gave at least 80% mortality: 1, 2, 4, 5, 7, 8, 10, 11, 12, 13, 14, 16, 20, 21, 22, 23, 25, 26, 27, 28, 29, 31, 32, 33, 34, 36, 38, 39, 42, 43, 45, 46, 47, 49, 51, 52, 53, 54, 55, 56, 58, 59, 62, 63, 65, 66, 67, 77, 78, 79, 80, 81, 82, 87, 88, 90, 91, 93, 94, 96, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 111, 112, 113, 114, 115, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 131, 133, 135, 136.

TEST G

To assess the destruction of the whitefly magnoliaceae (Bemisia tabaci), the testing device consisted of a 14-21-day-old plants of cotton grown in the medium Redi-earth® (Scotts Co.), with at least two true leaves, infected nymphs 2nd and 3rd age stages on the underside of these leaves.

Compound (test compound) was prepared in acetone (not more than 2 ml) and then diluted with water to 25-30 ml of the Prepared compounds was applied using the spray tip is a flat nozzle for spraying (Spraying Systems 122440) at a rate of 10 psi (69 kPa). Plants were sprayed to runoff using a sprayer on a wheel (patent application EP-1110617-A1). All experimental compounds in this screening were sprayed at 250 hours/million and tested in three replicates. After spraying, the test-connection device for testing was kept for 6 days in the chamber for growing at 50-60% relative humidity and at a temperature of 28°in the daytime and 24°With at night. Then the leaves were removed and counted the dead and the living nymphs to calculate the percentage of mortality.

Of the tested compounds, the following compounds gave at least 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 39, 42, 43, 45, 46, 47, 49, 51, 52, 53, 54, 55, 56, 59, 77, 78, 79, 80, 81, 82, 87, 90, 93.

TEST N

To assess soil system suppression tobacco Cutworm (Heliothis virescens) and cotton plants were grown in the sassafras soil in containers with a diameter of 15 cm in aluminum trays. When the plants have reached the stage three podsvechnikov (sepals) of the flower of the cotton plant (the formation of buds on the plant, these plants were treated with test compounds.

Compound was prepared in 0.25 ml of acetone and then diluted with water to obtain solutions of 1, 5, 10 and 50 h/million 10 ml of solutions for processing was added to the vessels on a weekly basis for four weeks, with eirma the replicates for each target processing. Later, one day after the second, third and fourth treatments 35-50 larvae of Heliothis virescens first stages shook the brush on each plant and placed on the apical zone, three podvenica (sepals) of the flower of the cotton plant or seed pods. Five days after the last infection by the larvae of these plants were evaluated for damage. Of the tested compounds, the following compounds were provided excellent levels of plant protection at the rate of 10 h/m (10% or less damage as a result of eating): 16.

Of the tested compounds, the following compounds were also provided excellent protection three podsvechnikov and seed pods at the rate of 10 hours/million, with no damage as a result of eating or with minimal damage sepals: 16.

The TEST I

The test I conducted on alternative Protocol for assessing soil system suppression tobacco Cutworm (Heliothis virescens). The cotton plants were grown in the sassafras soil in containers with a diameter of 15 cm in the conditions of a greenhouse. When the plants have reached the stage three podsvechnikov flower cotton (during the formation of buds on the plant, the soil surface was treated with test compounds.

Compound (test compound) were prepared in 0.25 ml of acetone and then diluted with water. Ten ml solution for processing, soderjashie mg connections, added on the soil surface of each pot. Plants were watered the next day and every day after that as needed. 1, 2 and 4 days after treatment, the leaves were cut for evaluation. From each plant were selected two groups of leaves: upper leaves at approximately the second node from the top and with an area larger than 25 cm2and lower sheets at approximately the third node from the bottom and with an area larger than 25 cm2. Cut sheets cut into sections 3 cm × 2 cm and was placed in the test trays made of high-strength styrene, consisting of sixteen adjacent holes, each with a width of 6 cm, length 4 cm and a depth of 3 cm, with a transparent plastic cover, molded in such a way that it blocks the entrance of each hole by friction. In the lower part of each well was placed solidified agar to maintain moisture for plant material. One well tobacco second stages were placed in each well with plant material; the wells were sealed and kept at 25°providing 16 hours of light per day. For the leaves, cut at 1, 2 and 4 day mortality was observed 4 days after processing one tobacco Cutworm second age stage.

Of the tested compounds, the following compounds have been providing excellent levels of mortality (greater than 70% with ARTNeT) on the upper leaves, cut 4 days after treatment with the test norm: 2, 27, 33.

TEST J

To assess soil system suppression scoops herbal (Spodoptera frugiperda) corn (maize) (Pioneer #3394) were grown in small containers for 5 days, until they reached a height of at least 4 cm and the first sheet is not deployed.

Compound (test compound) was dissolved in 0.25 ml of acetone and diluted with water to obtain solutions of 1, 10, 50 and 200 hours/million 1 ml of test solution was applied by pipette to the surface of the soil in each vessel using eight plants for each connection/for each rule. The vessels were closed and kept at 25°providing 16 hours of light per day. Plants were watered the next day and every day after that as needed. After 6 days the crop above the first sheet cut and sliced into segments of length 3, refer to Each device for testing was high strength styrene tray (Provider: Clearpack Company, 11610 Copengagen Court, Franklin Park, IL 60131), which consists of sixteen adjacent holes, each with a width of 6 cm, length 4 cm and a depth of 3 cm, with a transparent plastic cover, molded in such a way that it blocks the entrance to the hole by friction. In the lower part of each well was placed solidified agar (2-4 ml) to maintain humidity during the test. Each segment 3 cm R is stenia corn was placed in the tray so this plant material was kept in two holes. One well herbal (Spodoptera frugiperda) second stages were placed in each well of the tray closed and then these devices for testing kept at 25°With 16 hours of light per day. Mortality was observed after four days.

Concentration LC90(the concentration of test compounds that provide 90% killing of the larvae (caterpillars)) was calculated by using probit analysis (logarithmic linear regression) using the General linear model (GLIM) package SAS statistical computer analysis of SAS Institute (Cary, NC, U.S.A.). Of the tested compounds, the following compounds have been providing excellent levels of mortality with values LC9010 hours/million or less: 1, 2, 4, 9, 11, 12, 14, 16, 20, 22, 24, 31, 32, 33, 34.

TEST

To evaluate the suppression of the Colorado potato beetle (Leptinotarsa decemlineate) sample of 5 mg of the test compound (test compound) was dissolved in 1 ml acetone. Then this solution was diluted to 100 ml total volume using an aqueous solution of 500 ppm, surfactants Ortho X-77™. Was prepared by serial dilution to obtain 50 ml concentration of 10 h/million

Diluted solutions of test compounds were sprayed to runoff on a three-week plant potatoes or tomatoes. These plants were placed on a rotating sprayer by turning to the uge (10 rpm). The test compounds were applied using the spray tip with a flat spray nozzle (Spraying Systems 122440) at the rate of 10 pounds per square inch (69 kPa). After drying, each of the treated plants cut off the processed leaves of this plant. The leaves are cut into pieces, which were placed one per cell 5.5cm × 3.5 cm shestnadtsatietazhnogo plastic tray. Each cell contained a square of 2.5 cm hydrated chromatography paper to prevent drying. One larva of the second age were placed in each cell. Three days after infection were registered, the total number of dead Colorado potato beetles.

Of the tested compounds, the following compounds were led to at least 90% mortality at the rate of 10 ppm: 2, 4, 27, 33, 34, 41, 61, 85.

TEST L

To assess the destruction weevil cotton (Anthonomus g. grandis) samples of the tested compounds were dissolved in 1 ml acetone. Then this solution was diluted to 100 ml total volume using an aqueous solution of 500 ppm, surfactants Ortho X-77™. Was prepared by serial dilution to obtain 50 ml of a concentration of 50 PM/million

Diluted solutions of test compounds were sprayed to runoff at three weeks of the cotton plant. These plants were placed on a rotating sprayer on a wheel (10 rpm). Test-connection h is worn using a circular saw trimming tip with a flat spray nozzle (Spraying Systems 122440) at the rate of 10 psi (69 kPa). Sprayed and dried, the plants were placed in a plastic cylinder. Twenty weevils were placed in each cylinder containing whole plant cotton. Three days after infection was estimated damage as a result of eating.

Of the tested compounds, the following compounds were provided excellent levels of plant protection at 50 hours/million (10% or less damage as a result of eating): 20, 27.

TEST M

To assess the destruction of thrips (Frankliniella sp.) samples of the tested compounds were dissolved in 1 ml acetone. Then this solution was diluted to 100 ml total volume using an aqueous solution of 500 hours/million surfactants Ortho X-77™. Was prepared by serial dilution to obtain 50 ml concentration of 10 h/million

Diluted solutions of test compounds were sprayed to runoff on a three-week plant cotton or soybeans infested with thrips. These plants were placed on a rotating sprayer on a wheel (10 rpm). The test compounds were applied using the spray tip with a flat spray nozzle (Spraying Systems 122440) at the rate of 10 psi (69 kPa). Sprayed and dried plants were concluded in a plastic cylinder. Three days after the application was assessed by the total number of dead thrips.

Of the tested compounds, the following compounds were led is to at least 90% mortality at the rate of 10 hours per million): 32.

TEST N

To assess the suppression of the development of the nematode root growths (Meloidogyne incognita) when using contact and/or systemic action used test device consisting of a small open container placed inside the tomato seedlings age 7-9 days. The composition of the test compounds were received and were sprayed with the content of 250 hours/million, repeating the operation three times as described for test A. After spraying the test device was left alone to dry for 1 hour, and then the pipetting was introduced into the soil approximately 250 young larvae stage 2 (J2) and then superimposed over the black shielding cover. The test device was kept for 6 days at 25°C and 65-70% relative humidity. Then, for each test unit conducted a visual assessment of damage to the roots.

Among the tested compounds excellent levels of plant protection (70% or more reduction of the root galloroman) showed the following: 20.

TEST P

For evaluation of the fight against potato leafhopper (Empoasca fabae Harris) through contact and/or systemic means, each test unit consisted of a small open container containing within 5-6 days legume Longio (appearing first is mi leaves). Top soil was added to the white sand and one of the first leaves cut off before applying. Test compounds were formulated as described above, and sprayed three times as described for Test A. After spraying the test units were allowed to dry for 1 hour, and then they were infected with 5 potato cicadae (adult 18-21 days). Top each container was placed black obscured by the cover. The test unit was kept for 6 days in the cell for growth if 19-21°C and 50-70% relative humidity. Each test unit was then visually examined for mortality of insects.

The Q TEST

To assess combat cicadas corn (Peregrinus maidis) through contact and/or systemic means, each test unit consisted of a small open cylindrical container, containing within 3-4-day plant corn (maize). On top of soil were added white sand, and one of the first leaves cut off before applying. Test compounds were formulated as described above, and sprayed three times as described for Test A. After spraying the test units were allowed to dry for 1 hour, and then they were infected 10-20 cicadas corn (nymphs 18-21 days), spraying them on the sand by means of a shaker. Top each container was placed black blocking cap is ku. The test unit was kept for 6 days in the cell for growth if 19-21°C and 50-70% relative humidity. Each test unit was then visually examined for mortality of insects.

TEST R

To assess the suppression of cycatki potato (Empoasca fabae Harris) use of funds contact and/or systemic action each test unit consisted of a small open container placed inside the bean sprouts, Longo aged 5 to 6 days (with the appearance of the primary leaves). On top of the soil inflicted pure quartz sand, and one of the primary leaves before applying cut. Compositions for testing was as described above, and sprayed, repeating the operation 3 times as described for test A. After spraying the test device was left alone to dry for 1 hour before the conduct of their infection, using 5 tikatok potato (adult aged 18 to 21 days). Top each container was placed black shielding cover. The test device was kept for 6 days in a growth chamber at 19-21°C and 50-70% relative humidity. Then, for each test unit conducted a visual assessment of the mortality of the insects.

Next presents data illustrating the attachment is sustained fashion effects observed with the introduction of known active compound or agent in a composition comprising a compound of formula 1 (tables G, H and J1-J6).

The active ingredients listed in Table G, was tested in accordance with the Protocol described for TEST A, TEST E TEST F TEST G, as described above; TEST protocols P and Q TEST described above. Compounds were prepared in the form of compositions, using a solution containing 10% acetone, 90% water and 300 hours/million nonionic surfactant X-77® Spreader Lo-Foam Formula, containing alkalinisation, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.), obtaining the concentration of the test solutions of 1, 10, 100, and 250 hours/million Then the composition of the test solutions were sprayed and evaluated in accordance with the protocols.

Rooms compounds (other than the names of compounds)listed in the first column of the table G, specify the connection number specified in the Index Table A. Insecticidal activity are listed in Table G in categories a, b, C, D and E. "A" means the lowest concentration of active ingredient required to suppress a specific pest for more than 90%, is 1 h/m or less; "B" means 10 h/m or less; "C" means 100 h/m or less; "D" means 250 hours per million or less; and "E" means more than 250 hours/million the other words, the connection of category "a" is at least 100 times more active than compound "C"category.

TABLE G
Insecticidal activity of the compounds according to claim 1 in combination with known biologically active compounds
The mode of actionConnectionISPA DBM*ISPE GPA*.F MCA*.G WF*ISPR PLH*ICP-Q NRC*
The neonicotinoidsacetamipridInAndInAnd
The neonicotinoidsclothianidinInInInIn
The neonicotinoidsImidaclopridAndAndAnd
The neonicotinoidsthiaclopridInInAndIn
amitrazEEEEE
Ȁ thiamethoxamAndInAndAnd
chlorfenapyrInEEIn
pyridabenInInIn
pyridalylIn
flonicamidEInInED
pymetrozineDInInEEIn
the chlorpyrifosEEEE
carbamatesMetforminEInIn
carbamatesoxamylEED
carb is mats thiodicarbEEInIn
PyrethroidsdeltamethrinAndE
PyrethroidsesfenvalerateAndEAndE

E In
Blockers of Na channelsindoxacarbAndEE
PyrethroidsLambda cigalotrinAndInDAndAnd
buprofezinEEEEEIn
cyromazineEEEEE
Insecticidal ureahexaflumuronEEEEE
Insecticidal ureal is fenuron InIn
Insecticidal ureanovaluronAndEEEEE
methoxyfenozideAndEE
tebufenozideDEE
Macrocyclic lactonesthe abamectinAndAndInIn
Macrocyclic lactonesspinosadInEEEEE
Antagonists of GABAfipronilAndEInIn
Mimics juvenile hormonefenoxycarbInEEEE
Mimics juvenile hormonemethopreneInEEE
Mimics juvenile hormonepyriproxifenEEInEE
Connection 1AndAndDInE
Connection 2AndInInE
Connection 4AndInE
Connection 7AndAndInAndInE
Compound 8AndAndInInE
Connection 11AndInInInIn
Connection 12AndInInInE
The connection 16AndInE
The connection 20AndInInE

The connection 26AndInInIn
Connection 27AndDInE
The connection 33AndInDInE
The connection 34AndDEIn
The connection 43AndInInthe InE
Connection 47AndInInInIn
The connection 53AndInInE
The connection 55AndInInInE
Connection 79AndInInIn
Connection 87AndInInE
Connection 93And InInE
Connection 101AndInInInD
Connection 120AndInInSS
* Use Test; DBM means the cabbage moth, GPA means peach aphid, MCA means aphid cotton/melon; WF means whiteflies silverlief, PLH means Cicada potato and NRC means the Cicada corn.
TABLE N
Cicada cornConcentration (ppm)% mortalityConcentration (h/m)The ratio (A:B)% mortality
InThe connection 2050028
A1the abamectin40100A1+40+5001:12,5100
A2clothianidin10100A2+B10+5001:50100
A3thiamethoxam0,6100A3+0,6+5001:833100
A4thiacloprid3100A4+3+5001:167100
A5spinosad5100A5+5+5001:100100
Cicada potatoConcentration (ppm)% mortality&x0200A; Concentration (Cmin)The ratio (A:B)% mortality
InThe connection 205054
A1The abamectin100100A1+100+502:1100
A2Clothianidin1093A2+B10+501:5100
A6chlorfenapyr5100A6+5+501:10100

Aphid peachConcentration (ppm)% mortalityConcentration (ppm)The ratio (A:B) % mortality
InThe connection 201024
A1The abamectin0,4100A1+0,4+101:25100
A2clothianidin0,08100A2+B0,08+101:125100

The data presented in tables from J to J6 below, demonstrate that the treatment of pests with the use of a mixture or composition known biologically active compound or agent and the new compounds described by formula 1 (i.e., compound 20), clearly leads to increased percent mortality of the pest in comparison with the results of processing with the use of each ingredient, taken separately. In addition, these mixtures or compositions also illustrate the mass ratio between the compound described by formula 1, and additional biologically active compound or agent is in the range from 250: 1 to 1: 500.

Table J1
Western flower trip (test method described in the test M)
Western is th flower trip Rate (h/m)Ratio% mortality (observed)
The connection 2010046
Thiacloprid10030
The connection 20 + thiacloprid100+1001:160
Nitenpyram50080
The connection 20 + nitenpyram100+5001:590
Dinotefuran2060
The connection 20 + dinotefuran100+205:180
Chlorfenapyr15090
The connection 20 + chlorfenapyr100+1501:1,590

Fenoxycarb1040
The connection 20 + fenoxycarb100+1010:170
Fenoxycarb100060
The connection 20 + fenoxycarb100+10001:1080
Methoprene/td> 10060
The connection 20 + methoprene100+1001:180
Indoxacarb300050
The connection 20 + indoxacarb100+30001:3080
Triazamate1070
The connection 20 + triazamate100+1010:190
Tebufenozide10070
The connection 20 + tebufenozide100+1001:190
Oxamyl130
The connection 20 + oxamyl100+1100:170
Thiacloprid300040
The connection 20 + thiacloprid100+30001:3070
Table J2
Aphids green peach (test method described in test (E)
Aphids green peachRate (h/m)Ratio% mortality (observed)
With the unity 20 2035
Thiamethoxam0,494
The connection 20 + Thiamethoxam20+0,450:198
Nitenpyram15017
The connection 20 + nitenpyram20+1501:7,547
Novaluron100025
Compound 20 + novaluron20+10001:5049
Thiacloprid0,213
The connection 20 + thiacloprid20+0,2100:142
The connection 201024
Me haunted5020
The connection 20 + methomyl10+501:540
Chlorfenapyr736
The connection 20 + chlorfenapyr10+71,4:159

Spinosad100059
The connection 20 + spinosad10+10001:10072
Lufenuron25015
The connection 20 + lufenuron10+2501:2535
Lufenuron100028
The connection 20 + lufenuron10+10001:10049
Table J3
Aphid cotton/melon (test method described in test F)
Aphid cotton/melonRate (h/m)Ratio% mortality (observed)
The connection 202041
Methomyl1564
The connection 20 + methomyl20+151,3:181
Acetamiprid0,0867
The connection 20 + acetamiprid20+0,08250:185
Lufenuron0,439
The connection 20 + lufenuron20+0,450:166
Pyridalyl232
The connection 20 + pyridalyl20+210:159
Spinosad10035
The connection 20 + spinosad20+1001:562
Pyriproxifen100033
The connection 20 + pyriproxyfen20+10001:5059
Cyromazine1023
The connection 20 + cyromazine20+102:160
Indoxacarb1016
The connection 20 + indoxacarb20+102:151
Clothianidin0,0875
The connection 20 + clothianidin20+0,08250:184
Dinotefuran131
The connection 20 + dinotefuran20+0,0820:162
Hexaflumuron100030
With the Association 20 + hexaflumuron 20+10001:5065
Hydramethylnon150039
The connection 20 + hydramethylnon20+15001:7566

Table J4
The cabbage moth (test method described in test (a)
The cabbage mothRate (h/m)Ratio% mortality (observed)
The connection 200,0475
Dinotefuran2,560
The connection 20 + dinotefuran0,04+2,51:12590
Chromatin2060
The connection 20 + chromatin0,04+201:50090
Chlorfenapyr770
The connection 20 + chlorfenapyr0,04+71:17590
Table J5
Whiteflies magnoliaceae (test method described in test G)
Whiteflies magnoliaceaeRate (h/m)Ratio% mortality (observed)
The connection 2063
Acetamiprid2083
The connection 20 + acetamiprid6+201:3,391
The connection 20105
Acetamiprid2083
The connection 20 + acetamiprid10+201:287
Table J6
Cicada potato (test method described in the test R)
Cicada potatoRate (h/m)Ratio% mortality (observed)
The connection 205054
Fipronil0,57
The connection 20 + fipronil50+0,5100:160

1. Anthranilamide a compound selected from compounds of formula 1 or their N-oxides

where Rsup> 1means of CH3, F, Cl or Br;

R2means F, Cl, Br, I or CF3;

R3means CF3, Cl, Br or OCH2CF3;

R4ameans1-C4alkyl;

R4bmeans N or CH3; and

R5mean Cl or Br,

or is it acceptable for use in agriculture salt.

2. Anthranilamide compound according to claim 1, selected from compounds of the formula 1A or N-oxides

where R1means of CH3, Cl or Br;

R2means F, Cl, Br, I or CF3;

R3means CF3, Cl or Br;

R4means1-C4alkyl; and

R5mean Cl or Br,

or is it acceptable for use in agriculture salt.

3. The compound according to claim 1, where R4ameans1-C4alkyl, a R4bmeans H; or R4ameans of CH3and R4bmeans of CH3.

4. The compound according to claim 3, where R5means Cl.

5. The compound according to claim 4, where R4ameans of CH3CH2CH3CH(CH3)2or(CH3)3.

6. The compound according to claim 5, where R2mean Cl or Br.

7. The connection according to claim 6, where R1means of CH3.

8. The connection according to claim 7, where R1means Cl.

9. The compound according to claim 1, which is selected from the group consisting of

the compounds of formula 1, where R1means of CH3, R2means Br, R3means CF3, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Br, R3means CF3, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Br, R3means Br, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Br, R3means Br, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Br, R3means Cl, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Br, R3means Cl, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means CF3, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means CF3, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means Br, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means Br, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means Cl, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means Cl, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means OCH2CF3, R4ameans CH(CH3)2, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means och2CF3, R4ameans of CH3, R4bmean N and R5mean Cl;

connect the s formula 1, where R1means Cl, R2means Cl, R3means Br, R4ameans of CH3, R4bmean N and R5mean Cl;

the compounds of formula 1, where R1means of CH3, R2means Cl, R3means och2CF3, R4ameans of CH3, R4bmean N and R5means Cl.

10. Composition for combating insects, containing a biologically effective amount of a compound according to claim 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

11. Composition for combating invertebrate pests, containing a biologically effective amount of a compound according to claim 1 and an effective amount of at least one additional biologically active compound or agent.

12. The composition according to claim 11, where at least one additional biologically active compound or an additional agent selected from arthropocidal group consisting of pyrethroids, carbamates, neonicotinoids, blockers of sodium channels of neurons, insecticidal macrocyclic lactones, antagonists γ-aminobutyric acid (GABA), insecticidal ureas and juvenile hormone mimetics.

13. The composition according to claim 11, where at least one additional biologists who Eski active compound or agent selected from insecticides, nematicides, acaricides or biological agents group consisting of abamectin, acephate, acetamiprid, midflame, embryo death, azadirachtin, azinphosmethyl, bifenthrin, bifenazate, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos, chromafenozide, clothianidin, spraying with cyfluthrin, beta-spraying with cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, giovanola, emamectin, endosulfan, esfenvalerate, ethiprole, fanatically, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flucythrinate, Tau-fluvalinate, fluphenazine, flufenoxuron, fonofos, halogenated, hexaflumuron, Imidacloprid, indoxacarb, isofenphos, lufenuron, Malathion, metaldehyde, metamidophos, mitigation, methomyl, methoprene, Methoxychlor, monocrotophos, methoxyfenozide, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, porata, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxifen, rotenone, spinosad, spiromesifen, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosulfat-sodium, tralomethrin, trichlorfon, triflumuron, aldicarb is a, oxamyl, fenamiphos, amitraz, chinomethionat, Chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, phenazocine, oxide fenbutatin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, including subspecies aizawai and kurstaki Delta-endotoxin of Bacillus thuringiensis, baculovirus, and entomopathogenic bacteria, virus and fungi.

14. The composition according to claim 11, where at least one additional biologically active compound or an additional agent selected from an insecticide, nematocide, acaricide or biological agents group consisting of cypermethrin, cyhalothrin, spraying with cyfluthrin and beta-spraying with cyfluthrin, esfenvalerate, fenvalerate, tralomethrin, fanatically, methomyl, oxamyl, thiodicarb, clothianidin, Imidacloprid, thiacloprid, indoxacarb, spinosad, abamectin, embryo death, emamectin, endosulfan, ethiprole, fipronil, flufenoxuron, triflumuron, giovanola, pyriproxifen, pymetrozine, amitraz, Bacillus thuringiensis Delta-endotoxin of Bacillus thuringiensis and mushrooms-entomophages.

15. A method of combating insects, involving contacting insects or their environment with a biologically effective amount of a compound according to claim 1.

16. A method of combating insects, involving contacting insects or surrounding the Reda with a biologically effective amount of the composition according to item 11.

17. The compound of formula 2

where R1means of CH3, F, Cl or Br;

R2means F, Cl, Br, I or CF3;

R3means CF3, Cl, Br or OCH2CF3; and

R5mean Cl or Br.

18. The compound of formula 4

where R3means CF3, Cl, Br or co2CF3; and

R5mean Cl or Br.

19. The method according to item 15, involving contacting plants with a compound of formula I, its N-oxide or its acceptable for use in agriculture salt, by irrigation of the soil liquid composition containing the specified connection.

20. The composition of claim 10 in the form of a liquid composition for irrigation of the soil.

Priority points and features:

13.08.2001 according to claim 1 in addition to R1=F, R3=Co2CF3, R4b=CH3p.2, p.3 except R4b=CH3, 4, 5, 6, 7, 8, where R1=Cl, item 9 (compound 1-12), except paragraph 10 R1=F, R3=Co2CF3, R4b=CH, 15, p in addition to R3=OCH2CF3;

21.09.2001 - § § 11-14, 16, 17 in R3=OCH2CF3, claim 19, claim 20;

02.04.2002 - 1 (R1=F, R3=OCH2CF3, R4b=CH3), p.3 (R4b=CH3), item 9 (compounds 13-16), paragraph 10 (R1=F, R3=OCH2CF3, R4b=CH3), 17(R 3=Co2CF3), p (R3=Co2CF3).



 

Same patents:

FIELD: organic chemical, pharmaceuticals.

SUBSTANCE: invention relates to new compounds having JAK3 kinase inhibitor activity, methods for production thereof, intermediates, and pharmaceutical composition containing the same. In particular disclosed are aromatic 6,7-disubstituted 3-quinolinecarboxamide derivatives of formula I and pharmaceutically acceptable salts thereof useful in production of drugs for treatment of diseases mediated with JAK3. In formula n = 0 or 1; X represents NR3 or O; Ar is selected from phenyl, tetrahydronaphthenyl, indolyl, pyrasolyl, dihydroindenyl, 1-oxo-2,3-dihydroindenyl or indasolyl, wherein each residue may be substituted with one or more groups selected from halogen, hydroxy, cyano, C1-C8-alkoxy, CO2R8, CONR9R10 C1-C8-alkyl-O-C1-C8-alkyl, etc., wherein R-groups are independently hydrogen atom or C1-C8-alkyl; meanings of other substitutes are as define in description.

EFFECT: new compounds having value biological properties.

17 cl, 222 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new sulfonamide derivatives possessing anti-tumor activity, namely to compounds of the formula (I): wherein R6 means hydroxyl; R7 means methyl, isopropyl, isobutyl, benzyl or indole-3-ylmethyl; R8 means hydrogen atom; R9 means phenylene; R10 means thienyl, furyl or pyridyl optionally substituted with lower alkyl or halogen atom. Also, invention relates to their derivatives or pharmaceutically acceptable salts or solvates. Invention describes medicinal agents used in treatment or prophylaxis of cancer and for prophylaxis of metastasis. Also, invention describes a case for treatment of cancer in mammal.

EFFECT: improved treatment method, valuable medicinal properties of agent.

5 cl, 17 tbl, 112 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes using 2-morpholyl-6-piperidyl-4-[(4'-(ethoxycarbonyl-5'-1',2',3'-triazol)-1'-yl]-1,3,5-triazine of the formula: as an antidote against phytotoxic effect of herbicide 2,4-dichlorophenoxyacetic acid on sunflower germinated seeds. The proposed substance allows significant increasing roots and hypocotyls length of seedlings and to expand assortment of the known antidotes.

EFFECT: improved and valuable properties of antidote.

2 cl, 2 tbl, 3 ex

FIELD: organic chemistry, medicine, virology.

SUBSTANCE: invention relates to new derivatives of piperidine of the general formula (II): or their pharmaceutically acceptable salts wherein Xa means -C(R13)2-, -C(R13)(R19)-, -C(O)-, and others; Ra means R6a-phenyl or phenyl substituted with methylsulfonyl; R1 means hydrogen atom or (C1-C6)-alkyl; R2 means R7-, R8-, R9-phenyl wherein R7-, R8 and R9 mean substituted 6-membered heteroaryl and others; R3 means R10-phenyl, pyridyl and others; R4 means hydrogen atom, (C1-C6)-alkyl, fluoro-(C1-C6)-alkyl; R6a means from 1 to 3 substitutes taken among the group involving hydrogen, halogen atom, -CF3 and CF3O-; R7 and R8 mean (C1-C6)-alkyl and others; R9 means R7, hydrogen atom, phenyl and others; R10 means (C1-C6)-alkyl, -NH2 or R12-phenyl wherein R12 means hydrogen atom, (C1-C6)-alkyl and others; R13, R14, R15 and R16 mean hydrogen atom or (C1-C6)-alkyl; R17 and R18 in common with carbon atom to which they are bound form spirane ring comprising from 3 to 6 carbon atoms; R19 means R6-phenyl wherein R6 means R6a or methylsulfonyl; R20, R21 and R22 mean hydrogen atom or (C1-C6)-alkyl; R23 means (C1-C6)-alkyl under condition that if Ra means phenyl substituted with methylsulfonyl then Xa can mean the group only. Compounds of the formula (II) possess properties of CCR5-antagonist and can be used in medicine in treatment of HIV-infection.

EFFECT: improved method for treatment, valuable medicinal properties of compounds and composition.

15 cl, 1 dwg, 12 tbl, 15 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention describes a new compound 4,6-bis-(morpholyl)-2-[(2'-ethoxyacetyltetrazolyl)-5'-yl]-1,3,5-triazine of the formula: that represents an antidote against phytotoxic effect of herbicide 2,4-dichlorophenoxyacetic acid on germinating sunflower seeds and seedlings.

EFFECT: valuable properties of compound.

2 cl, 2 tbl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:

wherein Ag represents (1) group of the formula:

; (2) group represented by the formula:

or ; (3) group represented by the formula:

; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:

; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.

EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.

40 cl, 51 tbl, 741 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new substituted derivatives of pyrrole of the formula (I): wherein R1 and R1' mean independently hydrogen atom (H) or (lower)-alkyl, unsubstituted or substituted (lower)-alkoxy-group; R2 means hydrogen atom (H), nitro-group (-NO2), cyano-group (-CN), halogen atom, unsubstituted (lower)-alkyl or substituted with halogen atom or (lower)-alkoxy-group; R2' means thiazolyl, thiophenyl, isothiazolyl, furanyl and pyrazolyl that is unsubstituted or substituted with (lower)-alkyl, pyrimidinyl, unsubstituted morpholinyl, unsubstituted pyrrolidinyl and imidazolyl that is unsubstituted or substituted with (lower)-alkyl, unsubstituted piperidinyl or piperazinyl that is unsubstituted or substituted with (lower)-alkyl, or ethoxy-group substituted with imidazolyl, or its pharmaceutically acceptable salt. Compounds of the formula (I) inhibit cell proliferation in G2/M phase of mitosis that allows their using in the pharmaceutical composition.

EFFECT: valuable biological properties of compounds.

36 cl, 4 sch, 1 tbl, 21 ex

FIELD: organic chemistry, heterocyclic compounds, medicine.

SUBSTANCE: invention relates to derivatives of piperazine and piperidine of the formula (I): wherein ---Z represents =C or -N; Q means benzyl or 2-, 3- or 4-pyridylmethyl that can be substituted with one or more substitutes taken among group comprising halogen atom, cyano-group, (C1-C3)-alkoxy-group, CF3, OCF3, SCF3, (C1-C4)-alkyl, (C1-C3)-alkylsulfonyl and their salts, and to a method for their preparing also. It has been found that these compounds elicit valuable pharmacological properties owing to combination of (partial) agonism with respect to members of dopamine receptors subtype and affinity with respect to corresponding serotonin and/or noradrenergic receptors and can be useful in preparing compositions used in treatment of fear and/or depression or Parkinson's disease.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 3 ex

FIELD: organic chemistry, medicinal biochemistry, pharmacy.

SUBSTANCE: invention relates to substituted benzimidazoles of the formula (I): and/or their stereoisomeric forms, and/or their physiologically acceptable salts wherein one of substitutes R1, R2, R3 and R4 means a residue of the formula (II): wherein D means -C(O)-; R8 means hydrogen atom or (C1-C4)-alkyl; R9 means: 1. (C1-C6)-alkyl wherein alkyl is linear or branched and can be free of substituted by one-, bi- or tri-fold; Z means: 1. a residue of 5-14-membered aromatic system that comprises from 1 to 4 heteroatoms as members of the cycle that represent nitrogen and oxygen atoms wherein aromatic system is free or substituted; 1.1 a heterocycle taken among the group of oxadiazole or oxadiazolone that can be unsubstituted or substituted; 2. (C1-C6)-alkyl wherein alkyl is a linear or branched and monosubstituted with phenyl or group -OH; or 3. -C(O)-R10 wherein R10 means -O-R11, -N(R11)2 or morpholinyl; or R8 and R9 in common with nitrogen atom and carbon atom with that they are bound, respectively, form heterocycle of the formula (IIa): wherein D, Z and R10 have values given in the formula (II); A means a residue -CH2-; B means a residue -CH-; Y is absent or means a residue -CH2-; or X and Y in common form phenyl. The cyclic system formed by N, A, X, Y, B and carbon atom is unsubstituted or monosubstituted with (C1-C8)-alkyl wherein alkyl is monosubstituted with phenyl, and other substitutes R1, R2, R3 and R4 mean independently of one another hydrogen atom, respectively; R5 means hydrogen atom; R6 means the heteroaromatic cyclic system with 5-14 members in cycle that comprises 1 or 2 nitrogen atoms and can be unsubstituted or substituted. Also, invention relates to a medicinal agent for inhibition of activity of IkB kinase based on these compounds and to a method for preparing the indicated agent. Invention provides preparing new compounds and medicinal agents based on thereof for aims for prophylaxis and treatment of diseases associated with the enhanced activity of NFkB.

EFFECT: valuable medicinal properties of compounds and composition.

4 cl, 7 tbl, 224 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of azole of the formula:

wherein R1 represents (1) halogen atom; (2) nitrogen-containing 5- or 6-membered heterocyclic group comprising from 1 to 4 nitrogen atoms as atoms of ring system in addition to carbon atoms, and group with condensed rings comprising nitrogen-containing 5- or 6-membered heterocyclic group comprising 1-2 nitrogen atoms as atoms of ring system in addition to carbon atoms, and benzene ring wherein nitrogen-containing 5- or 6-membered heterocyclic group and group with condensed rings can comprise optionally from 1 to 3 substituted taken among group consisting of: (i) aliphatic hydrocarbon group comprising from 1 to 15 carbon atoms; (ii) (C6-C14)-aryl group, and (iii) carboxy-group that can be in form of group of (C1-C6)-alkyl ester wherein above indicated substitutes (i)-(iii) can have from 1 to 3 substituted additionally taken among group consisting of: (a) carboxyl group and (b) hydroxy-group; (3) (C1-C10)-alkylsulfanyl group that can be substituted with hydroxy-group; (4) heteroarylsulfanyl group taken among pyridylsulfanyl, imidazolylsulfanyl and pyrimidinylsulfanyl, or (5) amino-group that can be mono- or di-substituted optionally with substitutes(substitutes) among group consisting of: (i) (C1-C10)-alkyl group that can be substituted with hydroxy-group, and (ii) (C7-C10)-aralkyl group; Ab represents aryloxy-group that is substituted with alkyl group and can be substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkyl group, hydroxy-group or (C1-C6)-alkylcarbonyloxy-group additionally; B represents (C6-C14)-aryl group or thienyl group each of that can has optionally from 1 to 4 substitutes taken among halogen atom, (C1-C6)-alkoxy-group and (C1-C6)-alkyl group that can has optionally from 1 to 3 halogen atoms; Y represents saturated aliphatic bivalent group with direct or branched chain and having from 1 to 7 carbon atoms, or to its salt. Also, invention relates to a pharmaceutical composition that elicits activity for promoting production/secretion of neurotrophine, and to methods for prophylaxis and treatment based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof used for prophylaxis and treatment of neuropathy.

EFFECT: improved and valuable medicinal properties of agent, improved methods for treatment.

19 cl, 1 dwg, 5 tbl, 122 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to ortho-substituted arylamides of formula I , wherein J represents phenyl ring or pyrazole ring each substituted with one or two substitutes independently selected from R5; K represents -NR1C(=A)- or -NR1SO2-; L represents -C(=B)NR2-, -SO2NR2- or -C(=B)-; A and B represent O; R1 and R2 represent H; R3 represents C1-C6-alkyl optionally substituted with one or more substitutes, independently selected from group containing CN, NO2, C1-C4-alkylsulfonyl and C2-C6-alkoxycarbonyl; each R4 independently represents C1-C6-alkyl, halogen or CN; each R5 independently represents C1-C6-alkyl, halogen or C1-C4-haloalkoxy or pyridinyl optionally substituted with one substitute independently selected from R9; wherein R9 represents halogen; n = 1-2; with the proviso, that when K represents -NR1C(=A)- L is not -C(=B)NR2-, and salts thereof, method for insect controlling by using abovementioned compounds. Intermediate for synthesis of target compounds having formula 2 also is disclosed.

EFFECT: compounds with insecticide activity, useful in insect controlling.

15 cl, 21 tbl, 9 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to heterocyclic compounds of general formula I with PGl2 receptor agonist activity. In formula R1 and R2 represent independently optionally substituted phenyl; Y represents N, N-O or CR5; Z represents N or CR6; A represents NR7; D represents alkylene or alkenylene; or A and D may together form divalent group; E represents phenylene or direct bond, or D and E may together form divalent group; G represents O, S, SO, SO2; R3 and R4 represent hydrogen atom or alkyl; Q represents carboxyl, alkoxycarboxyl, tetrazolyl, carbamoyl or -CONH-SO-R10 group. Prostaglandin I2(PGl2) is potent inhibitor of platelet aggregation and may be effectively used in treatment of vascular diseases, arteriosclerosis, hypertension, etc.

EFFECT: new compounds and drugs for platelet aggregation inhibition and treatment of vascular and other diseases.

15 cl, 3 tbl, 109 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to derivatives of pyridazinone or triazinone represented by the following formula, their salts or their hydrates: wherein each among A1, A2 and A3 represents independently of one another phenyl group that can be optionally substituted with one or some groups chosen from the group including (1) hydroxy-group, (2) halogen atom, (3) nitrile group, (4) nitro-group, (5) (C1-C6)-alkyl group that can be substituted with at least one hydroxy-group, (6) (C1-C6)-alkoxy-group that can be substituted with at least one group chosen from the group including di-(C1-C6-alkyl)-alkylamino-group, hydroxy-group and pyridyl group, (7) (C1-C6)-alkylthio-group, (8) amino-group, (9) (C1-C6)-alkylsulfonyl group, (10) formyl group, (11) phenyl group, (12) trifluoromethylsulfonyloxy-group; pyridyl group that can be substituted with nitrile group or halogen atom or it can be N-oxidized; pyrimidyl group; pyrazinyl group; thienyl group; thiazolyl group; naphthyl group; benzodioxolyl group; Q represents oxygen atom (O); Z represents carbon atom (C) or nitrogen atom (N); each among X1, X2 and X3 represents independently of one another a simple bond or (C1-C6)-alkylene group optionally substituted with hydroxyl group; R1 represents hydrogen atom or (C1-C6)-alkyl group; R2 represents hydrogen atom; or R1 and R2 can be bound so that the group CR2-ZR1 forms a double carbon-carbon bond represented as C=C (under condition that when Z represents nitrogen atom (N) then R1 represents the unshared electron pair); R3 represents hydrogen atom or can be bound with any atom in A1 or A3 to form 5-6-membered heterocyclic ring comprising oxygen atom that is optionally substituted with hydroxyl group (under condition that (1) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; and each among A1, A2 and A3 represents phenyl group, (2) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o,p-dimethylphenyl group; A2 represents o-methylphenyl group, and A3 represents phenyl group, or (3) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o-methylphenyl group; A2 represents p-methoxyphenyl group, and A3 represents phenyl group, and at least one among R2 and R means the group distinct from hydrogen atom) with exception of some compounds determined in definite cases (1), (3)-(8), (10)-(16) and (19) given in claim 1 of the invention. Compounds of the formula (I) elicit inhibitory activity with respect to AMPA receptors and/or kainate receptors. Also, invention relates to a pharmaceutical composition used in treatment or prophylaxis of disease, such as epilepsy or demyelinization disease, such as cerebrospinal sclerosis wherein AMPA receptors take part, a method for treatment or prophylaxis of abovementioned diseases and using compound of the formula (I) for preparing a medicinal agent used in treatment or prophylaxis of abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

32 cl, 10 tbl, 129 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of 4-phenylpyridine of the following general formulae: (IA)

and (IB) wherein R1 means and , or -NH(CH2)2OH, -NR3C(O)CH3 or -NR3C(O)-cyclopropyl; R2 means methyl or chlorine atom; R3 means hydrogen atom or methyl; R means hydrogen atom or -(CH2)2OH; n = 1 or 2, and their pharmaceutically acceptable acid-additive salts. Also, invention describes a medicinal agent possessing effect of agonist of NK-1 receptors based on these compounds. Proposed compounds show good affinity degree to NK-1 receptors and can be used in treatment or prophylaxis of diseases associated with these receptors.

EFFECT: valuable medicinal properties of compounds and agent.

10 cl, 1 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes using compound of the general formula (I): wherein R1 means hydrogen atom or radical -X-Y-R4 wherein -X-Y- means a bond, radical -CO-O-, -CO-NH- or -CS-NH-; R4 means alkyl, cycloalkyl or aralkyl; R2 means aryl possibly substituted 4 times with halogen atom, alkyl, alkoxyl or aryl; R3 means hydrogen atom, or a pharmaceutically acceptable salt for preparing a medicinal agent designated for effect as a modulator of sodium channels. Also, invention describes a medicinal agent and pharmaceutical composition comprising compound of the formula (I)M given in the invention description as an active component. Modulators of sodium channels are used in therapy for withdrawal or prophylaxis of pain, migraine, post-operative pains, in epilepsy treatment and in other cases.

EFFECT: valuable medicinal properties of compounds.

13 cl, 26 ex

FIELD: organic chemistry, medicinal virology, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrazole of the formula (I-A):

wherein R1 means (C1-C12)-alkyl that can be optionally substituted with 1-3 substitutes taken among fluorine, chlorine and bromine atoms, (C3-C8)-cycloalkyl, phenyl, pyridyl or (C1-C4)-alkyl substituted with phenyl; R2' means optionally substituted phenyl wherein phenyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano- and nitro-group; R3 means (C1-C12)-alkyl or (C1-C4)-alkoxy-(C1-C4)-alkyl; A' means (C1-C4)-alkyl optionally substituted with phenyl or optionally substituted with 4-pyridyl wherein phenyl or 4-pyridyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH2-U-heterocyclyl wherein U represents O, S or NR'' wherein R'' means hydrogen atom or (C1-C4)-alkyl and wherein heterocyclyl means pyridyl or pyrimidinyl that is optionally substituted with 1-2 substitutes taken among (C1-C4)-alkyl, fluorine, chlorine and bromine atoms, cyano-, nitro-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH(OH)-phenyl; or A' means the group CH=CHW wherein W means phenyl; X means S or O, and their pharmaceutically acceptable salts. These compounds are inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and, therefore, can be used in treatment of HIV-mediated diseases. Also, invention relates to a pharmaceutical composition used in treatment of HIV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 5 tbl, 32 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes phenylpyridazine compounds represented by the following formula (I): wherein R1 represents unsubstituted or substituted phenyl wherein substitutes are taken among the group comprising halogen atom, lower alkyl, lower alkoxy-group and phenylthio-group, or pyridyl; R2 represents lower alkoxy-group, lower alkylthio-group, lower alkylsulfinyl or lower alkylsolfonyl; R3 represents hydrogen atom or lower alkoxy-group; or R2 and R3 can be condensed in common forming lower alkylenedioxy-group; R4 represents cyano-group, carboxyl, unsubstituted or substituted lower alkyl wherein substitutes are taken among the group comprising hydroxyl, carboxyl and N-hydroxy-N-lower alkylaminocarbonyl; lower alkenyl; lower alkylthio-group; lower alkylsulfinyl; lower alkylsulfonyl; lower alkylsulfonyloxy; unsubstituted or substituted phenoxy-group wherein substitutes are taken among the group comprising halogen atom, lower alkoxy-, nitro-, cyano-group; unsubstituted phenylthio-group or phenylthio-group substituted with halogen atom; pyridyloxy-; morpholino-group; morpholinylcarbonyl; 1-piperazinylcarbonyl substituted with lower alkyl; unsubstituted or substituted amino-group wherein substitutes are taken among the group comprising lower alkyl, benzyl, phenyl that can be substituted with halogen atoms or lower alkoxy-groups, and n = 0, or their salts. Proposed compounds possess the excellent inhibitory activity against biosynthesis of interleukin-1β and can be used in preparing a medicinal agent inhibiting biosynthesis of interleukin-1β, in particular, in treatment and prophylaxis of such diseases as diseases of immune system, inflammatory diseases and ischemic diseases. Also, invention proposes intermediate compounds for preparing compounds of the formula (I). Except for, invention proposes a medicinal agent and pharmaceutical composition that inhibit biosynthesis of interleukin-1β and inhibitor of biosynthesis of interleukin-1β.

EFFECT: valuable medicinal properties of compounds and composition.

7 cl, 1 tbl, 66 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of 4-phenylpyridine N-oxides of the general formula (I) and their pharmaceutically acceptable acid-additive salts wherein R means hydrogen atom, lower alkyl or halogen atom; R1 means hydrogen atom; R2 and R2' mean independently of one another hydrogen, halogen atom, trifluoromethyl group, (lower)-alkoxy-group; or R2 and R2' can mean in common the group -CH=CH-CH=CH- optionally substituted with one or two substitutes taken among lower alkyl or (lower)-alkoxy-group; R3 and R3' mean independently of one another hydrogen atom, lower alkyl; R4 and R4' mean independently of one another -(CH2)mOR6 or lower alkyl; or R4 and R4' form in common with N-atom to which they are bound substituted R5-cyclic tertiary amine representing pyrrolidine-1-yl, piperidine-1-yl, piperazine-1-yl, morpholine-4-yl or 1,1-dioxomorpholine-4-yl; R5 means hydrogen atom, hydroxyl, -COOR3, -N(R3)CO-lower alkyl or -C(O)R3; R6 means hydrogen atom, lower alkyl; X means -C(O)N(R6)-, -N(R6)C(O)-; n = 0, 1, 2, 3 or 4; m = 1, 2 or 3. Also, invention describes a medicinal agent comprising these compounds. Compounds can be used as drugs in treatment or prophylaxis of diseases associated with antagonists of NK-1 receptor.

EFFECT: valuable medicinal properties of agent.

6 cl, 32 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of benzimidazole of general formulae (IV)

and

For compounds of the formula (IV): R represents hydrogen atom, (C1-C10)-alkyl and others; D represents phenyl or azaphenyl; n = 0; A, B and Q represent hydrogen atom, (C1-C10)-alkyl and others; Z represents a bond, (C1-C6)-alkylene or -CH2O-; R1 represents hydrogen atom, (C1-C10)-alkyl and others; R2 represents hydrogen atom. For compounds of the formula (IVA): n = 0; Z represents a bond, -CH2-, -CH2O-, -CH2CH2-; R represents hydrogen atom or (C1-C10)-alkyl; R1 represents hydrogen atom, (C3-C12)-cycloalkyl, benzyl and others; R2 represents hydrogen atom. Compounds of formulae (IV) and (IVA) possess affinity with respect to nociceptin and μ-receptors and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

18 cl, 5 tbl, 16 ex

FIELD: organic chemistry, medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to derivatives of 1,2-dihydropyridine of the general formula (I)

,

their salts or hydrates wherein Q means oxygen atom (O); R1, R2, R3, R4 and R5 are similar or different of one another and each radical means hydrogen atom, halogen atom, (C1-C6)-alkyl group or group represented by the formula: -X-A (wherein X means a simple bond, (C1-C6)-alkylene group); A means (C6-C14)-aromatic hydrocarbocyclic group or 5-14-membered aromatic heterocyclic group. Also, invention describes a method for preparing compounds and pharmaceutical composition. Compounds possess the strong inhibitory effect on AMPA receptors and/or kainate receptors.

EFFECT: improved preparing method, valuable properties of compounds and composition.

99 cl, 1 tbl, 414 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to ortho-substituted arylamides of formula I , wherein J represents phenyl ring or pyrazole ring each substituted with one or two substitutes independently selected from R5; K represents -NR1C(=A)- or -NR1SO2-; L represents -C(=B)NR2-, -SO2NR2- or -C(=B)-; A and B represent O; R1 and R2 represent H; R3 represents C1-C6-alkyl optionally substituted with one or more substitutes, independently selected from group containing CN, NO2, C1-C4-alkylsulfonyl and C2-C6-alkoxycarbonyl; each R4 independently represents C1-C6-alkyl, halogen or CN; each R5 independently represents C1-C6-alkyl, halogen or C1-C4-haloalkoxy or pyridinyl optionally substituted with one substitute independently selected from R9; wherein R9 represents halogen; n = 1-2; with the proviso, that when K represents -NR1C(=A)- L is not -C(=B)NR2-, and salts thereof, method for insect controlling by using abovementioned compounds. Intermediate for synthesis of target compounds having formula 2 also is disclosed.

EFFECT: compounds with insecticide activity, useful in insect controlling.

15 cl, 21 tbl, 9 ex

Up!