Cyanoanthranilamide compounds, compositions on base thereof and method for invertebrate pest control

Description:

The invention relates to cyanoanthranylamide compounds, their base compounds and process for controlling invertebrate pests and can be used in agriculture and other fields.

The control of invertebrate fish is extremely important for obtaining a high crop productivity. Damage caused by invertebrate fish to stored crops and those in the field can cause a considerable reduction in their productivity and these can result in increased preferences for the consumer. The control of invertebrate fish is also important in forestry, for greenhouse crops, decorative plants, crops for seedlings, fibrous and stored food products, horned cattle, in the household, as well as for public and animal health. Many products are commercially available for these purposes, but the need for new compounds, more effective, less expensive, less toxic, environmentally pure or having different modes of action persists.

Derivatives of A-acylantranilic acid of the formula i are known as anthropodicides

<img file="MD3864B2_D0001.tif" />

<img file="MD3864B2_D0002.tif" />

В

<img file="MD3864B2_D0003.tif" />

wherein, inter alia, A and В independently represent О or S; J represents an optionally substituted phenyl ring, a 5- or 6-membered heteroaromatic ring, a naphthyl ring system, or an aromatic system of the 8, 9 or 10-membered heterobicyclic ring; R¹ and R³ independently represents H or optionally substituted CrC6 alkyl; R² represents H or C 1 -C 6 alkyl, each R⁴ independently represents H, C 1 -C 6 alkyl₆, C 1 -C 5 haloalkyl₆, halogen or CN, and does not take values ​​from 1 to 4 [1].

The essence of the invention is that a compound of formula 1, N-oxide or its salt is claimed,

<img file="MD3864B2_D0004.tif" />

<img file="MD3864B2_D0005.tif" />

in which:

R¹ represents Me, Cl, Br or F;

R² represents F, Cl, Br or C 1 -C₄haloalkoxy;

R³ represents F, Cl or Br;

R⁴ represents H, CrC₄ alkyl, Сз-Qalchenyl; 3-C₄alkynyl, C3-C5 cycloalkyl or C₄-C6 cycloalkylalkyl, each optionally substituted with a substituent selected from the group consisting of halogen, CN, SMe, S (O) Me, S (O)₂Me and OMe;

R⁵ represents H or Me;

R⁶ represents H, F or Cl and

R⁷ represents H, F or Cl.

Compound, in which:

R¹ represents Me or Cl;

R² represents Cl, Br, OCF₂H, OCF₃ or OCH₂CF₃ and

R⁴ represents H, Me, Et, z-Pr, FBu, CH₂CN, CH (May) CH₂EMS or C (Me)₂CH₂SME.

Compound, in which:

R² represents Cl, Br or OCH₂CF₃;

R⁴ represents H, Me, Et or z-Pr and

R⁵ represents H.

Compound of formula 1, selected from the group consisting of:

MD 3864 In 2009.03.31

3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 3-chloro- 1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1H-pyrazole-5-carboxamide, 3-bromo-1 (3-chloro- 2-pyridinyl) -N- [4-cyano-2-methyl-6 - [(nietilaniino) carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 3-bromo-1 (3-chloro-2-pyridinyl) N- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -LH-pyrazole-5-carboxamide, 3-chloro-1- (3-chloro-2-pyridinyl) -N- [2-chloro-4-cyano-6 - [(methylamino) carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 3-bromo- N- [2-chloro-4-cyano-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide,

3-chloro-l- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [[(l-nietiletil) amino] carbonyl] phenyl] -LH-pyrazole-5-carboxamide,

3-Bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1H-pyrazole-5-carboxamide, 1 - (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [(dimethylamino) carbonyl] -6-methylphenyl] -3- (2,2,2-trifluoroethoxy) -LH-pyrazole-5-carboxamide, l- (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [[(l, l-dimethylethyl) amino] carbonyl] -6-methylphenyl] -3- (2,2,2-trifluoroethoxy ) 1 H-pyrazole-5-carboxamide,

3-chloro-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [(cyclopropylamino) carbonyl] -6-methylphenyl] -1H-pyrazole-5-carboxamide, and

3-bromo-l- (3-chloro-2-pyridinyl) -N- [4-cyano-2 - [[(cyclopropylmethyl) amino] carbonyl] -6-methylphenyl] -LH-pyrazole-5-carboxamide.

Composition for controlling invertebrate pests containing о effective biological amount of compound and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent.

Composition, in the form of a liquid composition for soil wetting.

A process for controlling invertebrate pests, which includes contact of pests with о effective biological amount of composition defined in claim 5, which moistens the soil.

In the above listings, the term "alkyl", used either alone or in compound words, such as "alkylthio" or "haloalkyl", includes branched or straight chain alkyl, such as methyl, ethyl, rc-propyl, Lpropil, or different butyl isomers. The term "halogen" either alone or in compound words, such as "haloalkoxy", includes fluorine, chlorine, bromine or iodine. Additionally, when used in compound words, such as, "Jyaloalkyl" or "haloalkoxy", said alkyl or alkoxy may be wholly or partially substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F3C, С1СН₂, CF3CH2 and CF3CCI2. Examples of "haloalkoxy" include CF3O, HCF₂O, CCI3CH2O, HCF2CH2CH2O and CF3CH2O.

One skilled in the art will recognize that not all nitrogen-containing heterocycles can form V-oxides, because nitrogen requires a solitary couple available for oxidation of the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles that can form / V-oxides. One skilled in the art will also recognize that tertiary amines can form V-oxides. Synthetic methods for preparing V-oxides of tertiary heterocycles and amines are well known to one skilled in the art, including oxidation of tertiary heterocycles and amines with acid peroxides such as m-chloroperbenzoic and peracetic acid (AMCPB), hydrogen peroxide, alkyl hydroperoxides such as z-butyl hydroperoxide, sodium perborate and dioxirane, such as dimethyldioxirane. These methods for the preparation of V-oxides have been extensively described and reviewed in the literature, see, for example: TL Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp. 748-750, SV Ley, Pergamon Press; M. Tisler and В. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp. 18-20, AJ Boulton and A. McKillop, Ed. Pergamon Press; MR Grimmett and В. RT Keene in Advances in Heterocyclic Chemistry, vol. 43, pp. 149-161, AR Katritzky, Ed. Academic Press; M. Tisler and В. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp. 285-291, AR Katritzky and AJ Boulton, Ed. Academic Press; and GWH Cheeseman and ESG Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392, AR Katritzky and AJ Boulton, Academic Press Ed.

The compounds of the present invention may exist as one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One of skill in the art will recognize that a stereoisomer may be more active and / or exhibit beneficial effects when enriched than another (other) stereoisomer (s) or when separated from another (other) stereoisomer (s). Additionally, the person in the art knows how to separate, bond and / or selectively prepare said stereoisomers. Accordingly, the present invention contains compounds selected from formula 1, V-oxides and salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers !, or as an optically active form.

Salts of the compounds of the invention include addition salts with organic or inorganic acids, such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicyl, tartaric, 4- toluenesulfonic or valeric. In the compositions and methods of the present invention, the salts of the compounds of the invention are preferably favorable for the agronomic and non-agronomic uses described herein.

Important are compounds of formula 1, in which:

R⁴ represents H or C 1 -C 6 alkyl₄ optionally substituted with a substituent selected from the group consisting of CN, EMS and OMe;

R⁵ represents H or Me;

MD 3864 In 2009.03.31

R⁶ represents H and

R⁷ represents H.

Preferred compounds due to cost, ease of synthesis and / or biological efficiency are;

Preferable 1. Compounds of formula 1, wherein

R¹ represents Me or Cl;

R² represents Cl, Br, CF₃, OCF₂H, OCF₃ or OCH₂CF₃ and

R⁴ represents H, Me, Et, z-Pr, Z-Bu, CH₂CN, CH (May) CH₂EMS or C (Me)₂SME.

Preferable 2. Compounds of formula 1, wherein

R² represents Cl, Br, CF₃, or OCH₂CF₃;

R⁴ represents H, Me, Et or / -Pr and

R⁵ represents H.

Important are the compounds of Preferred 1 and Preferable 2, wherein R⁶ represents H; and R⁷ represents H.

Preferred compositions of the present invention are those containing the above-mentioned preferred compounds. Preferred methods of use are those which include the above-mentioned preferable compounds.

Compounds of formula 1 may be prepared by one or more of the following methods and variations, as described in Schemes 1-20. Definitions of R¹, R², R³, R⁴ and R⁵ In the compounds of formulas 1-24 below they are as given in the essence of the invention, unless otherwise provided.

Compounds of formula 1 may be prepared by reaction of benzoxazinones of formula 2 with о amine of formula HNR⁴R⁵, as shown in Scheme 1. This reaction can proceed without solvent! or in a variety of suitable solvents including tetrahydrofiirane, diethyl ether, dioxane, toluene, dichloromethane or chloroform with optimum temperatures ranging from room temperature to reflux temperature of the solvent. The general reaction of benzoxazinones with amines for the production of anthranilamides is well documented in the chemical literature. For a review of the chemistry of benzoxazinones see Jakobsen et. al., Biorganic and Medicinal Chemistry 2000, 8, 2095-2103 and references cited therein. See also GM Coppola, J. Heterocyclic Chemistry 1999, 36, 563588. '

Scheme 1

R2

<img file="MD3864B2_D0006.tif" />

Compounds of formula 1 may also be prepared from haloan-tranyl diamides of formula 3 (wherein X represents halogen, preferably iodine or formula 3 with о metal cyanide (e.g. copper cyanide, zinc cyanide or potassium cyanide) ), optionally with or without a palladium catalyst (for example tetrakis (triphenylphosphine) palladium (0) or disclorobis (triphenylphosphine) palladium (II)) and optionally with or without о metal halide (copper iodide, zinc iodide or potassium iodide) in a suitable solvent, such as acetonitrile, A₍A-dimethylformamide or A-methylpyrrolidinone, optionally at temperatures ranging from room temperature to reflux temperature of the solvent, provides compounds of formula 1. The convenient solvent may also be tetrahydrofuran or dioxane when the palladium catalyst is used in the coupling reaction.

Scheme 2

MD 3864 In 2009.03.31

<img file="MD3864B2_D0007.tif" />

(X halogen)

Cyanobenzoxazinones of formula 2 may be prepared by the method shown in Scheme 3. Reaction of a halobenzoxazinone of formula 4 (wherein X represents halogen, preferably iodine or bromine) with metal cyanide using a similar coupling method, as described above. top of Scheme 2 (optionally with or without a palladium catalyst and optionally with or without the presence of a metal halide), provides a compound of formula 2.

Scheme 3

<img file="MD3864B2_D0008.tif" />

The cyanobenzoxazinones of formula 2 may also be prepared by the method described in detail in Scheme 4 by coupling a pyrazolcarboxylic acid of formula 5 with a cyanoantranilic acid of formula 6. This reaction includes the successive addition of methanesulfonic chloride in the presence of a tertiary amine, such as triethylamine or pyridine to a pyrazolcarboxylic acid of formula 5, followed by the addition of cyanoantranilic acid of formula 6, followed by the secondary addition of tertiary amine and methanesulfonic chloride.

Scheme 4

<img file="MD3864B2_D0009.tif" />

of

4) MeS (O) 2 Cl

NH₂

OO2H

<img file="MD3864B2_D0010.tif" />

Scheme 5 discloses another method for the preparation of benzoxazinones of formula 2 which includes coupling an isotonic anhydride of formula 7 with pyrazolic acid chloride of formula 8. Solvents, such as pyridine or pyridine / acetonitrile, correspond to this reaction. The acid chlorides of formula 8 are available from the acids suitable for formula 5 by known methods, such as thionyl chloride or oxalyl chloride.

Scheme 5

MD 3864 In 2009.03.31

<img file="MD3864B2_D0011.tif" />

<img file="MD3864B2_D0012.tif" />

As shown in Scheme 6, haloantranyl diamides of formula 3 can be prepared by the reaction of benzoxazinones of formula 4, wherein X represents halogen, with о amine of formula HNR⁴R⁵ using о similar method, as described above for Scheme 1. The conditions for this reaction are similar to those specified in Scheme 1.

Scheme 6 r2

<img file="MD3864B2_D0013.tif" />

X— halogen

As shown in Scheme 7, the halobenzoxazinones of formula 4 (wherein X represents halogen) can be prepared by directly coupling a carboxylic pyridylpyrazole of formula 5 with a haloantranilic acid of formula 9 (in which X represents halogen) through a similar method, as described above for Scheme 4. This reaction includes the successive addition of methanesulfonic chloride in the presence of a tertiary amine, such as triethylamine or pyridine, to a pyrazolcarboxylic acid of formula 5, followed by the addition of a haloantranilic acid of formula 9, followed by the secondary addition of tertiary amine and methanesulfonic chloride. This method generally provides good yields of benzoxazinone.

Scheme 7

<img file="MD3864B2_D0014.tif" />

4) MeS (O) 2 Cl

As shown in Scheme 8, о halobenzoxazinone of formula 4 can also be prepared by coupling an isotonic anhydride of formula 10 (wherein X represents halogen) with о chlorazole of pyrazolic acid of formula 8 by a similar method, as has been described above for Scheme 5.

Scheme 8

MD 3864 In 2009.03.31

<img file="MD3864B2_D0015.tif" />

Cyanoanthranyl acids of formula 6 may be prepared from haloanthranyl acids of formula 9, as shown in Scheme 9. Reaction of a haloantranilic acid of formula 9 (wherein X represents halogen) with о metal cyanide using the same coupling procedure described above. for Scheme 2 (optional with or without the presence of a metal halide) it provides a compound of formula 6.

Scheme 9

<img file="MD3864B2_D0016.tif" />

solvent metal chloride,

Pd catalyst (optional) metal halide (opposite)

<img file="MD3864B2_D0017.tif" />

X-Halogen

As illustrated in Scheme 10, cyanoisathic anhydrides of formula 7 can be prepared from cyanoantranyl acids of formula 6 by reaction with phosgene (or an equivalent phosgene, such as trifosgene) or an alkylchloroformate (of tetrahydrofuran).

ex. methyl chloro-formate) in a suitable solvent, such as toluene

Scheme 10

<img file="MD3864B2_D0018.tif" />

nh₂ phosgene or solvent alkylchloroformate

CO H

<img file="MD3864B2_D0019.tif" />

О

As shown in Scheme 11, haloantranyl acids of formula 9 can be prepared by direct halogenation of an unsubstituted anthranilic acid of formula 11 with 7V-chlorosuccinimide (NCS), A'-bromosuccinimide (NBS) or Niodosuccinimide (NIS), respectively. in solvents, such as .V, A'-dimeylformamide (DMF), to produce the corresponding halogenated acid of formula 9.

Scheme 11

<img file="MD3864B2_D0020.tif" />

As illustrated in Scheme 12, haloisatoic anhydrides of formula 10 can be prepared from haloantranyl acids of formula 9 by reaction with phosgene (or an equivalent phosgene, such as trifosgene) or an alkylchloroformate, e.g. methyl chloroformate, in a suitable solvent, such as toluene or tetrahydrofuran.

Scheme 12

MD 3864 In 2009.03.31

<img file="MD3864B2_D0021.tif" />

The carboxylic pyridylpyrazole acids of formula 5 can be prepared by the method described in Scheme 13. The reaction of pyrazole 12 with 2-halopyridine of formula 13 in the presence of a suitable base, such as potassium carbonate, in a solvent, such as potassium carbonate. , in a solvent, such as VA-dimethylformamide or acetonitrile, provides good yields of 1-pyridylpyrazole 14 with good specificity for desirable regiochemistry. Metallization 14 with lithium diisopropylamide (DAL) followed by quenching the lithium salt with carbon dioxide gives pyrazolcarboxylic acid of formula 5.

Scheme 13

R2

<img file="MD3864B2_D0022.tif" />

Pyrazoles 12, wherein R² represents CF3, Cl or Br are known compounds. Pyrazole 12, wherein R² represents CF₃, can be prepared by the procedures described in the literature (J. Fluorine Chem. 1999, 53 (1), 61-70). Pyrazoles 12, wherein R² represents Cl or Br, can also be prepared by the procedures described in the literature (H. Reimlinger and A. Van Overstraeten, Chem. Ber. 1966, 99 (10), 3350-7). An alternative method useful for the preparation of pyrazoles 12, wherein R² represents Cl or Br, is described in Scheme 14. Metallization of sulfamoyl pyrazole 15 with m-butyllithium followed by direct halogenation of the anion with either hexachlorethane (for R² being Cl) or with 1,2-dibromotetrachlorethane (for R² being Br) offers halogenated derivatives 16 (wherein R² represents Cl or Br). Removal of the sulfamoyl group with trifluoroacetic acid (ATF) at room temperature produces solvents again and in good yield to obtain pyrazoles 12, wherein R² represents, respectively, Cl or Br.

Scheme 14

<img file="MD3864B2_D0023.tif" />

1) и-BuLi, solvent -------->

2) R²CC1₂CC1₂R²

<img file="MD3864B2_D0024.tif" />

ATF

SOtNMc2

16

As an alternative to the method illustrated in Scheme 13, pyrazolcarboxylic acids of formula 5, wherein R² represents CF3, can also be prepared by the method described in Scheme 15. The reaction of a compound of formula 17 (wherein R^s represents alkyl С_ГС₄) with a suitable base in a suitable organic solvent provides the cyclized product of formula 18 after neutralization with an acid, such as acetic acid.

MD 3864 In 2009.03.31

Scheme 15

<img file="MD3864B2_D0025.tif" />

The corresponding base may be, for example, but not limited to, sodium hydride, potassium t-butoxide, sodium dimsil (CH₃S (O) CH₂-N / A⁺), alkali metal hydroxides or carbonates (such as lithium, sodium or potassium), tetraalkylammonium hydroxides or fluorides (such as methyl, ethyl or butyl), or 2- / errbutylimino-2-diethylamino-1,3-dimethylperhydro -l, 3,2-diazafosfonina. The suitable organic solvent may be, for example, but not limited to acetine, acetonitrile, tetrahydrofuran, dichloromethane, dimethylsulfoxide, or Ν, Α-dimethylformamide. The cyclization reaction is usually performed within a temperature limit of about 0 to 120 ° C. The effects of solvent, base, temperature and time of addition are all interdependent, and the choice of reaction conditions is important for minimizing the formation of by-products. A preferable base is tetra-butylammonium fluoride.

Dehydration of the compound of formula 18 to obtain the compound of formula 19, followed by the hydrolysis of the carboxylic ester group of the carboxylic acid into the carboxylic acid, affords the compound of formula 5. Dehydration is accomplished by treating with a catalytic amount of a suitable acid. This catalytic acid may be, for example, but not limited to, sulfuric acid. The reaction is usually conducted using an organic solvent. As one of ordinary skill in the art will understand, dehydration reactions can be conducted in a wide variety of solvents, for example acetic acid, in a temperature range generally between about 0 and 200 ° C, more preferably between about 0 and 100 ° C. Carboxylic esters of formula 19 can be converted to carboxylic acids of formula 5 by numerous methods including nucleophilic decomposition into anhydrous conduits or hydrolytic methods including the use of etheric bases or acids (see TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, ed. 2nd, John Wiley &amp; Sons, Inc., New York, 1991, 224-269 for a review of methods). For Scheme 15, the base-catalyzed hydrolytic methods are preferable. Convenient bases include alkali metal hydroxides (such as lithium, sodium or potassium). For example, the ester may be dissolved in a mixture of water and alcohol, such as ethanol. When treated with sodium hydroxide or potassium hydroxide, the ester is saponified to obtain the sodium or potassium salt of carboxylic acid. Acidification with a strong acid, such as hydrochloric acid or sulfuric acid, generates carboxylic acid of formula 5.

Compounds of formula 17, wherein R² represents CF₃, can be prepared by the method described in Scheme 16. Treatment of a hydrazine compound of formula 20 with о ketone of formula CH₃CHOIR² In a solvent, such as water, methanol or acetic acid, it produces hydrazone of formula 21.

Scheme 16

<img file="MD3864B2_D0026.tif" />

wherein R² represents CF₃ and R⁸ represents C 1 -C 4 alkyl.

One skilled in the art will recognize that this reaction may require catalysis by an optional acid and may also require elevated temperatures depending on the molecular substitution structure of the hydrazone of formula 21. The reaction of the hydra-zone of formula 21 with an alkylchlorooxalate in a A convenient organic solvent, such as, for example, but not limited to dichloromethane or tetrahydrofuran in the presence of an acid neutralizer, such as triethylamine, generates the compound of formula 17. The reaction is usually conducted at a temperature of about 0 to 100 ° C. The hydrazine compounds of formula 20 may be prepared by standard methods, such as by the reaction of the corresponding halopyridine of formula 13 with hydrazine.

As an alternative to the method illustrated in Scheme 13, pyrazolcarboxylic acids of formula 5, wherein R² represents Cl or Br, can also be prepared by the method described in Scheme 17. Oxidation of the compound of formula 22,

MD 3864 Fl 2009.03.31 optional in the presence of acid, provides the compound of formula 19, wherein R² represents Cl or Br. Hydrolysis of the function of the carboxylic ester in the carboxylic acid generates the compound of formula 5.

Scheme 17

<img file="MD3864B2_D0027.tif" />

₁₉ 5 wherein R⁸ represents C 1 -C 6 alkyl₄.

The oxidizing agent for converting a compound of formula 22 into a compound of formula 19 may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate (for example Oxonium®) or potassium permanganate. In order to obtain the complete conversion, at least one equivalent of the oxidizing agent against a compound of formula 22 should preferably be used between one or two equivalents. This oxidation is typically 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, dimethylearbonate and the like, or a polar aprotic organic solvent such as Α, Α-dimethylformamide, acetonitrile and others like that. Suitable acids for use in the oxidation phase include inorganic acids such as sulfuric acid, phosphoric acid and the like, and organic acids such as acetic acid, benzoic acid and the like. One to five equivalents of acids can be used. Preferably the oxidant is potassium persulfate, and the oxidation of sulfuric acid is preferably carried out in the presence of sulfuric acid. The reaction may be conducted by mixing the compound of formula 22 in the solvent and, if used, the desired acid. The oxidant can then be added at a convenient percentage. The reaction temperature typically ranges from as low as possible from about 0 ° to the boiling point of the solvent to obtain a reasonable reaction time for completion of the reaction. Suitable methods for converting the ester of formula 19 into the carboxylic acid of formula 5 are already described for Scheme 15.

Compounds of formula 22, wherein R² represents halogen and R⁸ represents C alkyl₂-C₄, may be prepared from the corresponding compounds of formula 23, as shown in Scheme 18.

Scheme 18

<img file="MD3864B2_D0028.tif" />

wherein R⁸ represents C 1 -C 6 alkyl₄. 22

Treating a compound of formula 23 with a halogenating reagent, usually in the presence of a solvent, provides the corresponding halocompound of formula 22. Halogenating reagents that may be used include phosphoric oxyhalides, phosphoric trihalogens, phosphorous pentahalogens, thionyl chloride, dihalotrialkylphosphorphosphorylans, , oxalyl chloride and phosgene. Phosphoric oxyhalogens are preferable. In order to achieve the complete conversion, at least 0.33 equivalents of phosphoric oxyhalide against the compound of formula 23 should preferably be used between about 0.33 and 1.2 equivalents. In order to achieve full conversion, at least 0.20 equivalents of phosphoric pentahalogenide against the compound of formula 23 should preferably be used between about 0.20 and 1.0 equivalents. Typical solvents for this halogenation include halogenated alkanes, such as dichloromethane, chloroform, chlorobutane and the like, solvent! aromatics such as benzene, xylene, chlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane, diethyl ether and the like, and solvent! polar apricots such as acetonitrile, Α ', Α'-dimctilformamide and the like. Optionally, an organic base such as triethylamine, pyridine, ATV-dimethylaniline or the like may be added. Addition of a catalyst, such as AT'V-dimethylformamide. it is also an option. Preferably it is the process in which the solvent is acetonitrile and lacks a base. Typically, no base and no catalyst is required when using the acetonitrile solvent. The preferred process is accomplished by mixing the compound of formula 23 in acetonitrile. Reach vol

MD 3864 Fl 2009.03.31 of halogenation is then added at a convenient time, and the mixture is then maintained at the desired temperature until the reaction is complete. The reaction temperature typically varies between 20 ° C and the boiling point of acetonitrile, and the reaction time is typically less than 2 hours. The mass of the reaction is then neutralized with an inorganic base, such as sodium bicarbonate, sodium hydroxyl and the like, or an organic base, such as sodium acetate. The desired product of formula 22 can be isolated by methods known to those skilled in the art, including by crystallization, extraction and distillation.

Alternatively, compounds of formula 22, wherein R² represents Br or Cl, can be prepared by treating the corresponding compounds of formula 22, wherein R² represents a different halogen (for example, Cl for the preparation of formula 22, wherein R² represents Br) or a group of sulfonaphs, such as / Moluensulfonate, benzene sulfonate and methanesulfonate, respectively, with hydrogen bromide or hydrogen chloride. By this method the halogen R² or the sulphonate substituent in the compound of formula 22 is replaced by Br or Cl from hydrogen bromide or hydrogen chloride, respectively. The reaction is conducted in a suitable solvent, such as dibromethane, dichloromethane, acetic acid, ethyl acetate or acetonitrile. The reaction may flow to or near atmospheric pressure or above atmospheric pressure in a pressure vessel. The halogenating reagent may be added as a gas to the reaction mixture which confines the solvent and the compound of formula 2. When R² In the initial compound of formula 22 represents a halogen, such as Cl, the reaction is preferably conducted in such a way as a meat sprayer or other suitable means to remove the hydrogen halide generated from the reaction. Alternatively, the halogenating reagent may first be dissolved in an inert solvent in which it is highly soluble (such as acetic acid) until contact with the compound of formula 23 is either solvent-free or soluble. The reaction may be between about 0 and 100 ° C, most conveniently close to ambient temperature (for example, about 10 to 40 ° C), and more preferably between about 20 and 30 ° C. Addition of a Lewis acid catalyst (such as aluminum tribromide for the preparation of formula 22, wherein R² represents Br) may facilitate the reaction. The product of formula 22 is isolated by ordinary methods known to those skilled in the art, including by extraction, distillation and crystallization.

The initial compounds of formula 22, wherein R² represents a group of sulfonaphs, can be prepared from the corresponding compounds of formula 23 by standard methods, such as treatment with sulfonyl chloride (e.g., p-toluenesulfonyl chloride) and base, such as tertiary amine (de triethylamine) in a suitable solvent, such as dichloromethane.

As an alternative to the method illustrated in Scheme 13, pyrazolcarboxylic acids of formula 5, wherein R² represents haloalkoxy, can be prepared to sow by the method described in Scheme 19. A compound of formula 23 is oxidized into a compound of formula 24. The reaction conditions for this oxidation are those described for the conversion of the compound of formula 22 into the compound of formula 19 in scheme 17.

Scheme 19

<img file="MD3864B2_D0029.tif" />

wherein R² represents haloalkoxy and R⁸ represents C 1 -C 6 alkyl₄.

The intermediate of formula 24 is then alkylated to form a compound of formula 19 (wherein R² represents haloalkoxy) by reaffaction with a suitable haloalkylating agent, such as a sulfonate or haloalkyl halide.

The reaction is conducted in the presence of at least one equivalent of a base. Suitable bases include inorganic bases such as alkali metal hydrides, hydroxides and carbonates (such as lithium, sodium or potassium) or organic bases such as triethylamine, diisopropylethylamine and l, 8-diazabicyclo [5.4.0] undec- 7-ene. The reaction is generally conducted in a solvent which can contain alcohols, such as methanol and ethanol, halogenated alkanes such as dichloromethane, aromatic solvents such as benzene, toluene and chlorobenzene, ethers such as tetrahydrofuran, and solvents. polar apricots, such as acetonitrile, Α, Ν-dimethylformamide and the like. Alcohol and polar aprotic solvents are preferable for use with inorganic bases. Potassium carbonate as a base and Α, Α-dimethylformamide or acetonitrile as a solvent are more preferred. The reaction is generally conducted between 0 and 150 ° C, most typically between ambient temperature and 100 ° C. The ester of formula 24 can then be converted to carboxylic acid of formula 5 by the methods already described for converting a compound of formula 19 into a compound of formula 5 in Scheme 15.

MD 3864 In 2009.03.31

Compounds of formula 23 may be prepared from compounds of formula 20, as described in Scheme 20. In this method, a hydrazine compound of formula 20 may react with a compound of formula 25 (a fumaric or maleic ester or a mixture thereof may be used) in the presence of a base or solvent.

Scheme 20

<img file="MD3864B2_D0030.tif" />

wherein R⁸ represents C 1 -C 6 alkyl₄.

The base used in Scheme 20 represents alco alkoxide metal salt, such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium m-butoxide, lithium ether-butoxide and the like. Polar aprotic organic solvents and polar protic solvents such as alcohols, acetonitrile, tetrahydrofuran, A './V-dimethylformamide may be used. dimethylsulfoxide and the like. Preferred solvents are alcohols, such as methanol and ethanol. In particular, it is preferred that the alcohol be similar to that which forms the maleic or fumaric ester and the base of the alkoxide. The reaction is typically conducted by mixing the compound of formula 20 and the solvent base. The mixture may be heated or cooled to the desired temperature and the compound of formula 25 may be added after a period of time. Typically, the reaction temperatures vary between 0 ° C and the boiling point of the solvent used. The reaction may be conducted at a pressure greater than atmospheric pressure to increase the boiling point of the solvent. Temperatures between about 30 and 90 ° C are generally preferable. The reaction can then be acidified by the addition of an organic acid, such as acetic acid and the like, or an inorganic acid, such as hydrochloric acid, sulfuric acid and the like. The desired product of formula 23 can be isolated by methods known to those skilled in the art, such as crystallization, extraction or distillation.

It has been recognized that certain reagents and reaction conditions described above for the preparation of compounds of formula 1 may not be compatible with certain functional groups present in intermediates. In these cases, the incorporation of the protection / deprotection sequences or the interconversions of the functional group in the synthesis will help to obtain the desired products. The use and choice of protecting groups will be evident to those skilled in the art in chemical synthesis (see, for example, TW Greene and PM Wuts, Protective Groups in Organic Synthesis, 2nd ed .; Wiley, New York, 1991 ). The person skilled in the art will recognize that, in some cases, after the introduction of a given reagent, as described in each individual scheme, it may be necessary to perform additional regulated synthetic stages, not described in detail, to complete the synthesis of compounds of formula 1. 0 person skilled in the art will also recognize that it may be necessary to combine the stages illustrated in the above schemes in a different order than that suggested by the particular sequence presented for the preparation of compounds of formula 1.

It is considered that the person skilled in the art, using the description, without further elaboration may use the present invention in its entirety. The following examples should therefore be considered as illustrative and in no case should they limit the description. The stages in the following examples illustrate how many steps are performed for each stage in a general synthetic transformation, and the reference material for each stage not necessarily must be prepared by a particular preparation process, the procedure of which is described in other examples. or stages. The ratios are by mass, except for the mixtures of the chromatographic solvent or if indicated otherwise. The parts and ratios for the chromatographic solvent mixtures are volumetric, unless the invention provides otherwise. spectra^]NMR are reported in ppm relative to tetramethylsilane; s means single, d - double, t triplet, q - quartet, m - multiplet, dd - double of doubles, dt - double of triples, and br s - wide singlet.

EXAMPLE 1 '

Preparation of 1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -3- (trifluoromethyl) -1 H -pyrazole-5-carboxamide

Stage A: Preparation of 2-amino-3-methyl-5-iodobenzoic acid

To the solution of 2-amino-3-methylbenzoic acid (Aldrich, 5 g, 33 mmol) in Υ, Α-dimethylformamide (30 mL) was added A-iodosuccinimide (7.8 g, 34.7 mmol), and the mixture The reagent was incubated overnight in a greased bath at 75 ° C.

After cooling, the reaction mixture was slowly quenched in ice water (100 mL) for precipitation. The ash-light solid obtained was filtered and washed four times with water and then placed overnight in a vacuum oven at 70 ° C for drying. The desired intermediate was isolated as an ash-solid (8.8 g).

1 H NMR (DMSO-rf₆): δ 7.86 (d, 1H), 7.44 (d, 1H), 2.08 (s, 3H).

Stage B: Preparation of 3-chloro-2- [3- (trifluoromethyl) -1 H -pyrazol-1-yl] pyridine

MD 3864 In 2009.03.31

To a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and 3- (trifluoromethyl) -pyrazole (83 g, 0.61 mol) in N, dry dimethylformamide (300 mL) was added carbonate. potassium (166.0 g, 1.2 mol) and the reaction was then heated to 11O ... 125 ° C for 48 hours. The reaction was cooled to 100 ° C and filtered through a Celite® diatomic filtration medium to remove solids. Α, Α-dimethylformamide and dichloropyridine surplus were removed by distillation under reduced pressure. The distillation of the product under reduced pressure (mp 139 ... 141 ° C, 7 mm) provided 113.4 g of the desired intermediate as a light-yellow oil.

1 H NMR (CDC 1₃): δ 8.45 (d, 1H), 8.15 (s, 1H), 7.93 (d, 1H), 7.36 (t, 1H), 6.78 (s, 1H).

Stage C: Preparation of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1/7-pyrazole-5-carboxylic acid

To a solution of 3-chloro-2- [3- (trifluoromethyl) -1 / 7-pyrazol-1-yl] pyridine (which is the product of stage B pyrazole) (105.0 g, 425 mmol) in dry tetrahydrofuran ( 700 mL) at -75 ° C was added via a cannula о lithium diisopropylamide solution at 30 ° C (425 mmol) in dry tetrahydrofuran (300 mL). The dark-red solution was stirred for 15 minutes, after which the carbon dioxide was bubbled at -63 ° C until the solution turned to a pale yellow and the exo-thermality ceased. The reaction was further stirred for 20 min and then quenched with water (20 mL). The solvent was removed under reduced pressure, and the reaction mixture was separated into ether and 0.5 N aqueous sodium hydroxide solution. The aqueous extracts were washed with ether (3x), filtered through a Celite® diatomic filter to remove the residual solids, and then acidified to a pH of about 4, in which an orange oil was formed. The aqueous mixture was stirred vigorously and additional acid was added to reduce the pH to 2.5 ... 3. The orange oil coagulated in a granular solid that was filtered, washed successively with water and hydrochloric acid and dried in vacuo at 50 ° C to obtain 130 g of title product as a not-white solid. The product of another reaction obtained by a similar procedure melted at 175 ... 176 ° C.

1 H NMR (DMSO -?): 67.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d, 1H).

Step D: Preparation of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1,7-pyrazol -5-yl] -6-iodo-8-methyl-4 // -3 , l-benzoxazin-4-one

To the solution of methanesulfonyl chloride (291 mL, 37.74 mmol) in actonitrile (50 mL) was added dropwise a mixture of 1- (3-chloro-2-pyridinyl) -3- (triyluoromethyl) -lf / -pyrazole-5-carboxylic acid (which is the product of stage C carboxylic acid) (10.0 g, 34.31 mmol) and triethylamine (4.78 mL, 34.31 mmol) in acetonitrile (50 mL) at -5 ° C. The reaction temperature was then maintained at 0 ° C during the successive addition of the reagents. After stirring for 20 min, 2-amino-3-methyl-5-iodobenzoic acid (which is the product of stage A) (9.51 g, 34.31 mmol) was added and stirring continued for another 10 min. The triethylamine solution (9.56 g, 68.62 mmol) in acetonitrile (15 mL) was then added dropwise, and the reaction mixture was stirred for 30 min, followed by the addition of methanesulfonyl chloride (2.91 mL). (37.74 mmol). The reaction mixture was heated to room temperature and stirred for 2 hours. The solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to afford 8.53 g of the title compound as о yellow solid.

1 H NMR (CDC 1₃): δ 8.59 (dd, 1H), 8.35 (d, 1H), 7.97 (dd, 1H), 7.86 (d, 1H), 7.49 (m, 2H), 1, 79 (s, 3H).

Step E: Preparation of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1-pyrazol5-yl] -6-cyano-8-methyl-4 H-3,1- benzoxazin-4-one

In the solution of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -lf7-pyrazol-5-yl] -6-iodo-8-methyl-4 / 7-3, benzoxazin4-one (i.e., stage D benzoxazinone product) (500 mg, 0.94 mmol) in tetrahydrofuran (10 mL) was added copper (I) iodide (180 mg, 0.094 mmol), tetrakis (triphenylphosphine) palladium (0 ) (5.4 mg, 0.047 mmol) and copper cyanide (I) (420 mg, 4.7 mmol) sequentially at room temperature. After heating the reflux mixture overnight with the additional reactant mixture, copper cyanide (I) (107 mg, 0.56 mmol) and tetrakis (triphenylphosphine) palladium (0) (325 mg, 0.28 mmol) were added and reflux continued. 1 hour. The reaction mixture changed its color, at which point the thin layer chromatography on the silica gel confirmed the completion of the reaction. The reaction mixture was then diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO₄) and concentrated under reduced pressure to obtain о yellow crude solid.

1 H NMR (CDCl 3): δ 8.59 (dd, 1H), 8.33 (d, 1H), 8.03 (d, 1H), 7.95 (d, 1H), 7.56 ( m, 2H), 1.88 (s, 3H).

Stage F: Preparation of 1- (3-Chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -3- (trifluoromethyl) -1 H -pyrazole-5-carboxamide

In the solution of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1,5-pyrazol-5-yl] -6-cyano-8-methyl-4 / 7-3, lbenzoxazin-4-one (ie, the product of stage E cyanobenzoxazinone) (200 mg, 0.46 mmol) in tetrahydrofuran (5 mL) was added dropwise ammonium hydroxide (0.5 mL, 12.8 mmol) at room temperature . The reaction mixture was stirred for 5 min, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The solvent of tetrahydrofuran was evaporated under reduced pressure, and the residual solid was purified by chromatography on silica gel to obtain 620 mg of the title compound, a compound of the present invention, as a solid which melts at 200 .. 202 ° C.

^]H NMR (CDC1)₃): δ 10.65 (s, lH), 8.43 (dd, lH), 7.9 (dd, lH), 7.67 (s, lH), 7.63 (s, lH), 7, 45 (m, 1H), 7.25 (s, 1H), 6.21 (bs, 1H), 5.75 (bs, 1H), 2.26 (s, 3H).

EXAMPLE 2

Preparation of 1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6 - [(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) -17 / -pyrazole-5-carboxamide

MD 3864 In 2009.03.31

Stage A: Preparation of 1- (3-chloro-2-pyridines]) - A- [4-iodo-2-methyl-6 [(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) -1 H -pyrazole -5-carboxamide

In the solution of 2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl-1 H -pyrazol-5-yl)] - 6-iodo-8-methyl-4-H-3, 1-benzoxazin4-one (i.e., the benzoxazinone product of Example 1, step D) (500 mg, 0.94 mmol) in tetrahydrofuran (15 mL) was added dropwise methylamine (2.0 M solution in THF, 1.4 mL (2.8 mmol) and the reaction mixture was stirred for 3 hours, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The solvent of tetrahydrofuran was evaporated under reduced pressure, and the residual solid was purified by chromatography on silica gel to obtain 400 mg of the above-mentioned compound as a yellow solid.

1 H NMR (CDC 1₃): δ 10.25 (s, lH), 8.45 (dd, lH), 7.85 (dd, lH), 7.55 (s, lH), 7.50 (s, lH), 7, 46 (s, 1H), 7.40 (s, 1H), 6.15 (d, 1H), 2.93 (d, 3H), 2.12 (s, 3H).

Stage V: Preparation of 1- (3-chloro-2-pyridinyl) -Y- [4-cyano-2-methyl-6 - [(methylamino) carbonyl] phenyl] -3- (trifluoromethyl) 1 H -pyrazole- 5-carboxamide

To the solution of 1- (3-chloro-2-pyridinyl) -A- [4-iodo-2-methyl-6 - [(methylamino) carbonyl] phenyl]] - 3- (trifluoromethyl] - - // pyrazole-5-carboxamide (i.e., the product of stage A diamide) (410 mg, 0.72 mmol) in tetrahydrofuran (8 mL) was added copper (I) iodide (24 mg, 0.126 mmol), tetrakis (triphenylphosphine) palladium (0) (70 mg, 0.060 mmol) and copper cyanide (I) (640 mg, 7.2 mmol) sequentially at room temperature. The reaction mixture was heated at reflux for 4.5 hours. Thin layer chromatography on silica gel confirmed the end of the reaction. The reaction mixture was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO₄) and concentrated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain 114 mg of the above-mentioned title compound, a compound of the present invention, as a white solid which melts at 214. 216 ° C.

^]H NMR (CDC1)₃): 5 10.70 (s, 1H) ', 8.46 (dd, 1H), 7.87 (dd, 1H), 7.57 (s, 2H), 7.45 (m, 1H), 7 , 31 (s, 1H), 6.35 (d, 1H), 2.98 (d, 3H), 2.24 (s, 3H).

EXAMPLE 3

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

Stage A: Preparation of 3-chloro-A, A-dimethyl-1 H -pyrazol-1-sulfonamide

To a solution of A-dimethylsulfamoylpyrazole (188.0 g, 1.07 mol) in dry tetrahydrofuran (1500 mL) at -78 ° C was added dropwise to a solution of 2.5 M glyc-butyl lithium (472 mL, 1.18 mol) in hexane keeping the temperature below -65 ° C. At the end of the addition, the reaction mixture was maintained at -78 ° C for an additional 45 minutes, after which a solution of hexachlorethane (279 g, 1.18 mol) in tetrahydrofuran (120 mL) was added dropwise. The reaction mixture was maintained for 1 hour at -78 ° C, heated to -20 ° C and then quenched with water (1 L). The reaction mixture was extracted with methylene chloride (4 x 500 mL); The organic extracts were dried over magnesium sulfate and concentrated. The crude product was then purified by chromatography on silica gel using methylene chloride as eluent to obtain 160 g of the above-mentioned title compound as a yellow oil.

1 H NMR (CDC 1₃): δ 7.61 (s, 1H), 6.33 (s, 1H), 3.07 (d, 6H).

Stage B: Preparation of 3-chloropyrazole

To trifluoroacetic acid (290 mL) was added dropwise 3-chloro-A, A-dimethyl-1 H -pyrazol-1-sulfonamide (ie, the product of stage A chloropyrazole) (160 g), the reaction mixture was stirred at the room temperature for 1.5 hours, after which it was concentrated under reduced pressure. The residue was added to hexane, the insoluble solids were filtered, and the hexane was concentrated to obtain the crude product as an oil. The crude product was subsequently purified by silica gel chromatography using ether / hexane (40:60) as eluent to obtain 64.44 g of the product with the aforementioned title as a yellow oil.

1 H NMR (CDCl 2): ​​δ 6.39 (s, 1H), 7.66 (s, 1H), 9.6 (br s, 1H).

Stage C: Preparation of 3-chloro-2- (3-chloro-1 H -pyrazol-1-yl) pyridine

To a mixture of 2,3-dichloropyridine (92.60 g, 0.629 mol) and 3-chloropyrazole (i.e., the stage B product) (64.44 g, 0.629 mol) in MN-dimethylformamide (400 mL) was added potassium carbonate (147.78 g, 1.06 mol), then the reaction mixture was heated at 100 ° C for 36 hours, cooled to room temperature and slowly poured into ice water. The precipitated solids were filtered and washed with water. The solid filter check was introduced into ethyl acetate, dried over magnesium sulfate and concentrated. The crude solid was chromatographed on silica gel using 20% ​​ethylacetate / hexane as eluent to obtain 39.75 g of the product with the aforementioned title as a white solid.

Η NMR (CDCl3): δ 6.43 (s, 1H), 7.26 (m, 1H), 7.90 (d, 1H), 8.09 (s, 1H), 8.41 (d, H).

Step D: Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-carboxylic acid

To a solution of 3-chloro-2- (3-chloro-17 / -pyrazol-1-yl) pyridine (i.e., the C-stage pyrazole product) (39.75 g, 186 mol) in dry tetrahydrofuran (400 mL ) at -78 ° C a solution of 2.0 M lithium diisopropylamide (93 mL, 186 mmol) in tetrahydrofuran was added dropwise. The carbon dioxide was bubbled through amber solution for 14 minutes, after which the solution became brownish-yellow. The reaction was made basic with IN aqueous sodium hydroxide solution and extracted with ether (2x500 L). The aqueous extracts were acidified with 6N hydrochloric acid, followed by extraction with ethylacetate (3x500 mL). The extracts of ethyl acetate were dried over magnesium sulfate and concentrated

MD 3864 Fl 2009.03.31 to obtain 42.96 g of product with the aforementioned title as о solid not even white substance. The product of another reaction obtained by the same procedure melted at 198 ... 199 ° C.

1 H NMR (DMSO 4): δ 6.99 (s, 1H), 7.45 7.93 (d, 1H), 8.51 (d, 1H).

Step E: Preparation of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4 // -3-l benzoxazin-4-one

To the solution of methanesulfonyl chloride (0.63 mL, 8.13 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 3-chloro-1 (3-chloro-2-pyridinyl) -17 / -pyrazole-5-carboxylic acid (i.e., the D-stage carboxylic acid product) (2.0 g, 7.75 mmol) and triethylamine (1.08 mL, 7.75 mmol) in acetonitrile (5 mL) at 0 ° C . The reaction mixture was stirred for 15 min at 0 ° C. Thereafter, 2-amino-3-methyl-5-iodobenzoic acid (i.e., the product of Example 1, stage A) (2.14 g, 7.75 mmol) was added and stirring continued for 5 min. The triethylamine solution (2.17 mL, 15.15 mmol) in acetonitrile (5 mL) was added dropwise at a temperature below 5 ° C. The reaction mixture was stirred for 40 min at 0 ° C, then methanesulfonyl chloride (0.63 mL, 8.13 mmol) was added, warmed to room temperature and stirred overnight. It was then diluted with water (50 mL) and extracted with ethylacetate (3x50 mL). The combined ethylacetate extracts were washed successively with 10% aqueous sodium bicarbonate solution (1x20 mL) and salt solution (1x20 mL), dried (MgSO₄) and concentrated to obtain 3.18 g of the product with the aforementioned title as о yellow crude solid.

1 H NMR (CDC 1₃): δ 8.55 (dd, lH), 8.33 (s, lH), 7.95 (dd, lH), 7.82 (d, lH), 7.45 (m, lH), 7, 16 (s, 1H), 1.77 (s, 3H).

Stage F: Preparation of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-47L3, benzoxazine-4-one

In the solution of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-4 / 7-3, benzoxazin-4-one (i.e., the product of stage E benzoxazinone) (600 mg, 1.2 mmol) in tetrahydrofuran (15 mL) was added copper (I) iodide (137 mg, 0.72 mmol), tetrakis ( triphenylphosphine) palladium (0) (416 mg, 0.36 mmol) and copper cyanide (I) (860 mg, 9.6 mmol) sequentially at room temperature. The reaction mixture was then heated under reflux overnight. The reaction turned black, at which point the thin layer chromatography on the silica gel confirmed the completion of the reaction. The reaction was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO₄) and concentrated under reduced pressure to obtain 397 mg of the title compound as о yellow crude solid.

1 H NMR (CDC 1₃): δ 8.50 (q.lH), 8.22 (d, lH), 7.90 (dd.lH), 7.67 (d, lH), 7.45 (m, lH), 7, 15 (s, 1H), 1.79 (s, 3H).

Stage G: Preparation of 3-chloro-L (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (methylamino) carbonyl] phenyl] -17L pyrazole-5-carboxamide

To a solution of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-4 H-3, benzoxazin-4-one (eg, the product of stage F cyanobenzoxazinone) (100 mg, 0.25 mmol) in tetrahydrofuran (5 mL) was added dropwise methylamine solution (2.0 M solution in THF, 0.5 mL (1.0 mmol) and the reaction mixture was stirred for 5 minutes, at this point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain the above-mentioned compound, a compound of the present invention, as a white solid (52 mg), which decomposed. in a melting device above 140 ° C.

1 H NMR (CDC 1₃): δ 10.55 (s, 1H), 8.45 (dd, lH), 7.85 (dd, lH), 7.55 (d, 2H), 7.40 (m, lH), 6, 97 (d, 1H), 6.30 (d, 1H), 2.98 (d, 3H), 2.24 (d, 3H).

EXAMPLE 4

Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -V- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1 H -pyrazole-5-carboxamide

To a solution of 2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-8-methyl-4 H-3, benzoxazin-4-one (ie, the product of cyanobenzoxazinone from Example 3, stage F) (100 mg, 0.25 mmol) in tetrahydrofuran (5 mL) was added dropwise ammonium hydroxide (0.5 mL, 12.8 mmol) ) at room temperature. The reaction mixture was then stirred for 5 min, at which point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetra-hydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to obtain 55 mg of the title compound, a compound of the present invention, as a white solid which decomposes into a device for melting at temperatures above 255 ° C.

NMR (CDCl3): δ 10.50 (s, lH), 8.45 (dd, lH), 7.85 (dd, lH), 7.66 (d, lH), 7.61 (s, lH) , 7.41 (m, 1H), 6.95 (s, 1H), 6.25 (bs, 1H), 5.75 (bs, 1H), 2.52 (s, 3H).

EXAMPLE 5

Preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6 [(methylamino) carbonyl] phenyl] -1 H -pyrazole-5-carboxamide

Stage A: Preparation of 3-bromo-A, A-dimethyl-1Z / -pyrazole-1-sulfonamide

To the solution of Α, Ν-dimethylsulfamoylpyrazole (44.0 g, 0.251 mol) in dry tetra-hydrofuran (500 mL) at -78 ° C was added dropwise to a solution of «-butillithium (2.5 M in hexane, 105.5 mL, 0.264 mol) with a temperature lower than -60 ° C, resulting in о thick solid substance. After completion of the addition, the reaction mixture was maintained for a further 15 min, after which a solution of 1,2-dibromo-tetrachlorethane (90 g, 0.276 mol) in tetrahydrofuran (150 mL) was added via

MD 3864 Fl 2009.03.31 drip with keeping the temperature below -70 ° C. The reaction mixture was transformed into a pure orange; stirring was continued for a further 15 min. The bath at -78 ° C was removed and the reaction was quenched with water (600 mL). The reaction mixture was extracted with methylene chloride (4x), and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was subsequently purified by chromatography on silica gel using methylene chloride-hexane (50:50) as eluent to obtain 57.04 g of the product with the aforementioned title as a colorless pure oil.

1 H NMR (CDC 1₃): δ 3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m, 1H).

Stage B: Preparation of 3-brompirazole

To trifluoroacetic acid (70 mL) was slowly added 3-bromo-A, A-dimethyl-1/7-pyrazol-1-sulfonamide (i.e., the product of stage A brompirazole) (57.04 g). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The residue was introduced into hexane, the insoluble solids were filtered, and the hexane was evaporated to obtain the crude product as an oil. The crude product was subsequently purified by silica gel chromatography using ethyl acetate / dichloromethane (10:90) as eluent to obtain an oil. The oil was introduced into dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with methylene chloride (3x), dried over magnesium sulfate and concentrated to afford 25.9 g of the product with the above title as a white solid, mp 61 .. .64 ° C.

1 H NMR (CDC 1₃): δ 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H).

Stage C: Preparation of 2- (3-bromo-1 H -pyrazol-1-yl) -3-chlorphenine

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-brompyrazole (i.e., the product of stage V) (25.4 g, 176 mmol) in dried AjV-dimethylformamide (88 mL). potassium carbonate (48.6 g, 352 mmol) was added and the reaction mixture was heated at 125 ° C for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 mL). A precipitate formed. The precipitated solids were stirred for 1.5 hours, filtered and washed with water (2x100 mL). The solid filter check was introduced m methylene chloride and washed successively with water, IN hydrochloric acid, saturated aqueous sodium bicarbonate solution and salt solution. The organic extracts were then dried over magnesium sulfate and concentrated to give 39.9 g of pink solid. The crude solid was passed into hexane and stirred vigorously for 1 hour. The solids were filtered, washed with hexane and dried to give the product with the aforementioned title as a not even white powder (30.4 g) determined to be> 94% pure by NMR. This material was used after further purification in stage D.

1 H NMR (CDC 1₃): 8 6.52 (S, 1H), 7.30 (dd, 1H), 7.92 (d, 1H), 8.05 (s, 1H), 8.43 (d, 1H).

Step D: Preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -mazazole-5-carboxylic acid

To a solution of 2- (3-bromo-1/7-pyrazol-1-yl) -3-chlorpyridine (i.e., the product of step C pyrazole) (30.4 g, 118 mmol) in dried tetrahydrofuran ( 250 mL) at -76 ° C was added dropwise to a solution of lithium diisopropylamide (118 mmol) in tetrahydrofuran in such a ratio to maintain temperatures below -71 ° C. The reaction mixture was stirred for 15 minutes at -76 ° C and carbon dioxide was then bubbled for 10 minutes, causing heating to -57 ° C. The reaction mixture was heated to -20 ° C and quenched with water, concentrated and introduced into water (1 L) and ether (500 mL), after which aqueous sodium hydroxide solution (IN, 20 mL) was added. The aqueous extracts were washed with ether and acidified in hydrochloric acid. The precipitated solids were filtered, washed with water and dried to obtain 27.7 g of the product with the aforementioned title as a brownish-yellow solid. The product from another reaction using the similar procedure melted at 200 .. .201 ° C.

1 H NMR (DMSO-D: δ 7.25 (s, 1H), 7.68 (dd, 1H), 8.24 (d, 1H), 8.56 (d, 1H).

Stage E: Preparation of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-iodo-8-methyl-47/3, benzoxazin-4onei

To the solution of methanesulfonyl chloride (0.54 mL, 6.94 mmol) in acetonitrile (15 mL) was added dropwise a mixture of 3-bromo-1 (3-chloro-2-pyridinyl) -1 H -pyrazole-5-carboxylic acid (ie, the product of stage D carboxylic acid) (2.0 g, 6.6 mmol) and triethylamine (0.92 mL, 6.6 mmol) in acetonitrile (5 mL) at 0 ° C. The reaction mixture was stirred for 15 min at 0 ° C. Thereafter, 2-amino-3-methyl-5-iodobenzoic acid (ie, the product of Example 1, stage A) (1.8 g, 6.6 mmol) was added and stirring continued for a further 5 min. Then a solution of triethylamine (1.85 mL, 13.2 mmol) in acetonitrile (5 mL) was added dropwise, keeping the temperature below 5 ° C. The reaction mixture was stirred for 40 min at 0 ° C, followed by methanesulfonyl chloride (0.45 mL, 6.94 mmol). The reaction mixture was then warmed to room temperature and stirred overnight, then diluted with water (50 mL) and extracted with ethylacetate (3x50 mL). The combined ethylacetate extracts were washed successively with 10% aqueous sodium bicarbonate solution (1x20 mL) and salt solution (1x20 mL), dried (MgSO₄) and concentrated to obtain 2.24 g of the product with the aforementioned title as о yellow crude solid.

1 H NMR (CDC 1₃): δ 8.55 (dd, lH), 8.33 (d, lH), 7.95 (dd, lH), 7.85 (s, lH), 7.45 (m, lH), 7, 25 (s, 1H), 1.77 (s, 3H).

Stage F: Preparation of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -6-cyano-8-methyl-4 // -3, benzoxazin-4onei

In the solution of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1,4-pyrazol-5-yl] -6-iodo-8-methyl-4 / 7-3, benzoxazine-4-one (i.e., the stage E benzoxazine product) (600 mg, 1.1 mmol) in tetrahydrofuran (15 mL) was added copper (I) iodide (126 mg, 0.66 mmol), tetrakis ( triphenylphosphine) palladium (0) (382 mg, 0.33 mmol) and copper cyanide (I) (800 mg, 8.8 mmol) sequentially at room temperature. The reaction mixture was then heated under reflux overnight.

MD 3864 In 2009.03.31

The reaction turned black, at that point the thin layer chromatography on the silica gel confirmed the completion of the reaction. The reaction mixture was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% sodium bicarbonate solution and о with salt solution. The organic extract was dried (MeSO₄) and concentrated under reduced pressure to obtain 440 mg of the compound with the above-mentioned title as a yellow crude solid.

1 H NMR (CDCl 3): δ 8.55 8.31 (d, 1H), 7.96 (dd, 1H), 7.73 (s, 1H), 7.51 (m, 1H), 7.31 (s, 1H), 1.86 (s, 3H).

Stage G: Preparation of 3-bromo-1- (3-chloro-2-pyridiml) - / V,; V-cyano-2-methyl-6 [(methylamino) carbomyl] feml-1 / pyrazole-5-carboxamide

In the solution of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1,1-pyrazol-5-yl] -6-cyano-8-methyl-4 / 7-3, benzoxazin-4-one (i.e., the F-step product) (100 mg, 0.22 mmol) in tetrahydrofuran (5 mL) was added dropwise methylamine (2.0 M solution in THF, 0.5 mL, 1, 0 mmol) and the reaction mixture was stirred for 5 min, at this point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to afford the above-mentioned compound, a compound of the present invention, as the white solid (41 mg), which was decomposed into a melting device above 180 ° C.

Ή NMR (CDC1₃): δ 10.55 (s, lH), 8.45 (dd, lH), 7.85 (dd, lH), 7.57 (s, 2H), 7.37 (m, lH), 7, 05 (s, 1H), 6.30 (d, 1H), 2.98 (d, 3H), 2.24 (s, 3H).

EXAMPLE 6

Preparation of 3-bromo-1 - (3-chloro-2-pyridinyl) -A- [4-cyano-2-methyl-6- (aminocarbonyl) phenyl] -1,7-pyrazole-5-carboxamide

In the solution of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1,1-pyrazol-5-yl] -6-cyano-8-methyl-4 / 7-3, benzoxazin-4-one (i.e., the product of cyanobenzoxazinone from Example 5, stage F) (100 mg, 0.22 mmol) in tetrahydrofuran (5 mL) was added dropwise ammonium hydroxide (0.5 mL, 12, 8 mmol) at room temperature. The reaction mixture was then stirred for 5 min, at which point the thin layer chromatography on silica gel confirmed completion of the reagent. The tetra-hydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to afford the above-mentioned compound, a compound of the present invention, as a white solid (36 mg), with a point melting above 255 ° C.

^]H NMR (CDC1)₃): δ 10.52 (s, lH), 8.45 (dd, lH), 7.85 (dd, lH), 7.65 (s, lH), 7.60 (s, lH), 7, 40 (m, 1H), 7.05 (s, 1H), 6.20 (bs, 1H), 5.75 (bs, 1H), 2.25 (s, 3H).

EXAMPLE 7

Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -A- [2-chloro-4-cyano-6 [(methylamino) carbonyl] phenyl] -1,7-pyrazole-5-carboxamide

Stage A. Preparation of 2-amino-3-chloro-5-iodobenzoic acid

To 0 solution of 2-amino-3-chloro-5-iodobenzoic acid (Aldrich, 5 g, 29.1 mmol) in MA-dimethylformamide (30 mL) was added A-iodosuccinimide (5.8 g, 26 mmol) and the reaction mixture was heated overnight at 60 ° C. The heating was removed and the reaction mixture was then slowly poured into ice water (100 mL) to precipitate a brownish-light solid. It was filtered and washed 4 times with water and then placed in a vacuum oven at 70 ° C for drying overnight. The desired intermediate was isolated as a coffee-based solid (7.2 g).

1 H NMR (DMSO-J): δ 7.96 (d, 1H), 7.76 (t, 1H).

Stage B: Preparation of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 / 7-pyrazol-5-yl] -6-iodo-4 / 7-3, 1 benzoxazin-4onei

To the solution of methanesulfonyl chloride (0.31 mL, 4.07 mmol) in acetonitrile (10 mL) was added dropwise a mixture of 3-chloro-1 (3-chloro-2-pyridinyl) -1 / 7-pyrazole-5-carboxylic acid (ie, the carboxylic acid product of Example 3, step D) (1.0 g, 3.87 mmol) and triethylamine (0.54 mL, 3.87 mmol) in acetonitrile (5 mL) at 0 ° C. The reaction mixture was then stirred for 15 min at 0 ° C. Thereafter 2-amino-3-chloro-5iodobenzoic acid (i.e., the product from stage A) (1.15 g, 3.87 mmol) was added and stirring continued for 5 min. The triethylamine solution (1.08 mL, 7.74 mmol) in acetonitrile (5 mL) was added dropwise, keeping the temperature below 5 ° C. The reaction mixture was stirred for 40 minutes at 0 ° C, after which methanesulfonyl chloride (0.31 mL, 4.07 mmol) was added. It was then warmed to room temperature and stirred overnight, further diluted with water (50 mL) and extracted with ethylacetate (3x50 mL). The combined ethylacetate extracts were washed successively with 10% aqueous sodium bicarbonate solution (1x20 mL) and salt solution (11x20 mL), dried (MgSO₄) and concentrated under reduced pressure. The residual solid was purified by chromatography on silica gel to give 575 g of the above-mentioned title compound as a crude yellow solid.

1 H NMR (CDCl 3): δ 8.55 (q, 1H), 8.39 (d, 1H), 8.04 (d, 1H), 7.94 (dd, 1H), 7.45 (m, 1H), 7.19 (s, 1H).

Step C: Preparation of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 / 7-pyrazol-5-yl] -6-cyano-4 // -3, 1 -benzoxazin4-one

To the solution of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 / 7-pyrazol-5-yl] -6-iodo-4 // -3, benzoxazine-4-one (i.e., the product of stage V benzoxazine) (575 mg, 1.1 mmol) in tetrahydrofuran (15 mL) was added copper (I) iodide (840 mg, 0.4 mmol), tetrakis ( triphenylphosphine) palladium (0) (255 mg, 0.22 mmol) and copper cyanide (I) (550

MD 3864 Fl 2009.03.31 mg, 5.5 mmol) sequentially at room temperature. The reaction mixture was then heated under reflux overnight. The reaction turned black, at this point the thin layer chromatography on silica gel confirmed the completion of the reaction. The reaction was diluted with ethylacetate (20 mL) and filtered through Celite®, followed by washing 3 times with 10% aqueous sodium bicarbonate solution and о with salt solution. The organic extract was dried (MgSO₄) and concentrated under reduced pressure to obtain 375 mg of the title compound as о crude yellow solid.

1 H NMR (CDC 1₃): δ 8.55 (q, lH), 8.36 (d.lH), 7.95 (m, 2H), 7.5 (m, lH).

Step D: Preparation of 3-chloro-1- (3-chloro-2-pyridinyl) - / V- [2-chloro-4-cyano-6 [(mctilamino) carbonyl] fcnyl] -1 H -pyrazol-5- carboxamide

To a solution of 8-chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1 H -pyrazol-5-yl] -6-cyano-4 H-3, benzoxazin-4-one (i.e., C-stage cyanobenzoxazinone product) (187 mg, 0.446 mmol) in tetrahydrofuran (5 mL) was added dropwise methylamine (2.0 M solution in THF, 0.5 mL, 1.0 mmol) and the reaction mixture was stirred for 5 min, at this point the thin layer chromatography on silica gel confirmed completion of the reaction. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to contain 49 mg of the above-mentioned title compound, a compound of the present invention, as a white solid which melted at 197. .200 ° C.

1 H NMR (CDCl 3): 8. 10.05 (bs, lH), 8.45 (q, lH), 7.85 (dd, lH), 7.70 (d, lH), 7.59 (d, 1H), 7.38 7.02 (s, 1H), 6.35 (d, 1H), 2.94 (d, 3H).

By the procedures described here in conjunction with the methods known in the art, the compounds inserted in Table 1. can be prepared. ethyl, Pr - propyl, z'-Pr - isopropyl, Bu - butyl and CN - cyano.

Table 1

<img file="MD3864B2_D0031.tif" />

Λ 5. r5

MD 3864 In 2009.03.31

<td>В *</td><td>Bl</td><td>Bl</td><td>в!</td><td>в!</td><td></td><td>Bl</td><td>bi</td><td>and</td>

<td>of</td><td>F</td><td>H</td><td>Η</td><td>of</td><td>of</td><td>F</td><td>H</td><td>H</td>

<td>of</td><td>F</td><td>Me</td><td>Η</td><td>Cl</td><td>BUT</td><td>F</td><td>Me</td><td>H</td>

<td>of</td><td>F</td><td>et</td><td>Η</td><td>of</td><td>of</td><td>F</td><td>et</td><td>H</td>

<td>Cl</td><td>F</td><td>i-Pr</td><td>Η</td><td>Cl</td><td>Cl</td><td>F</td><td>i-Pr</td><td>H</td>

<td>of</td><td>F</td><td>i-Bu</td><td>Η</td><td>of</td><td>of</td><td>F</td><td>i-Bu</td><td>H</td>

<td>Cl</td><td>F</td><td>CH₂CN</td><td>Η</td><td>of</td><td>Cl</td><td>F</td><td>CH₂CN</td><td>H</td>

<td>of</td><td>F</td><td>CHfMeJCPhSMe</td><td>Η</td><td>Cl</td><td>Cl</td><td>F</td><td>CH (Me) CH2SMe</td><td>H</td>

<td>of</td><td>F</td><td>Me ^ CH ^ CCME</td><td>Η</td><td>of</td><td>Cl</td><td>F</td><td>CţMe ^ EC ^ SMe</td><td>H</td>

<td>of</td><td>F</td><td>Me</td><td>Me</td><td>Cl</td><td>Cl</td><td>F</td><td>Me</td><td>Me</td>

<td>Cl</td><td>of</td><td>H</td><td>Η</td><td>Cl</td><td>of</td><td>of</td><td>H</td><td>H</td>

<td>Cl</td><td>Cl</td><td>Me</td><td>Η</td><td>Cl</td><td>of</td><td>Cl</td><td>Me</td><td>H</td>

<td>of</td><td>Cl</td><td>et</td><td>Η</td><td>Cl</td><td>Cl</td><td>Cl</td><td>et</td><td>H</td>

<td>of</td><td>Cl</td><td>/ Pr</td><td>Η</td><td>Cl</td><td>Cl</td><td>Cl</td><td>j-Pr</td><td>H</td>

<td>of</td><td>Cl</td><td>i-Bu</td><td>Η</td><td>Cl</td><td>Cl</td><td>of</td><td>i-Bu</td><td>H</td>

<td>of</td><td>of</td><td>CH₂CN</td><td>Η</td><td>Cl</td><td>Cl</td><td>of</td><td>CH₂CN</td><td>H</td>

<td>Cl</td><td>Cl</td><td>CH (Me) CH2SMe</td><td>Η</td><td>of</td><td>of</td><td>Cl</td><td>СН (Ме) СН₂ЗМе</td><td>H</td>

<td>Cl</td><td>of</td><td>C (Me) 2 CH₂SMe</td><td>Η</td><td>BUT</td><td>Cl</td><td>of</td><td>CB ^ ^ SMe CfMe</td><td>H</td>

<td>BUT</td><td>Cl</td><td>Me</td><td>Me</td><td>Cl</td><td>Cl</td><td>of</td><td>Me</td><td>Me</td>

<td>of</td><td>br</td><td>H</td><td>Η</td><td>of</td><td>of</td><td>br</td><td>H</td><td>H</td>

<td>of</td><td>br</td><td>Me</td><td>Η</td><td>Cl</td><td>Cl</td><td>br</td><td>Me</td><td>H</td>

<td>of</td><td>br</td><td>et</td><td>Η</td><td>of</td><td>of</td><td>br</td><td>et</td><td>H</td>

<td>Cl</td><td>br</td><td>j-Pr</td><td>Η</td><td>Cl</td><td>of</td><td>br</td><td>$ Pr</td><td>H</td>

<td>of</td><td>br</td><td>i-Bu</td><td>Η</td><td>of</td><td>of</td><td>br</td><td>t-Bu</td><td>H</td>

<td>of</td><td>br</td><td>2 CN</td><td>Η ί</td><td>Cl</td><td>of</td><td>br</td><td>CH₂CN</td><td>H</td>

<td>of</td><td>br</td><td>СЩМе) ^ СН2 Ме</td><td>Η</td><td>Cl</td><td>of</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>of</td><td>br</td><td>CfMe ^ EC ^ SMe</td><td>Η</td><td>Cl</td><td>Cl</td><td>br</td><td>C (Me)_?Cfi2SMe</td><td>H</td>

<td>of</td><td>br</td><td>Me</td><td>Me</td><td>Cl</td><td>of</td><td>br</td><td>Me</td><td>Me</td>

<td>br</td><td>F</td><td>H</td><td>Η</td><td>of</td><td>br</td><td>F</td><td>H</td><td>H</td>

<td>br</td><td>F</td><td>Me</td><td>Η</td><td>of</td><td>br</td><td>F</td><td>Me</td><td>H</td>

<td>br</td><td>F</td><td>et</td><td>Η</td><td>of</td><td>br</td><td>F</td><td>et</td><td>H</td>

<td>br</td><td>F</td><td>i-Pr</td><td>Η</td><td>of</td><td>br</td><td>F</td><td>HPR</td><td>H</td>

<td>br</td><td>F</td><td>f-Bu</td><td>Η</td><td>of</td><td>br</td><td>F</td><td>/ -Bu</td><td>H</td>

<td>br</td><td>F</td><td>СН₂СЬ1</td><td>Η</td><td>Cl</td><td>br</td><td>F</td><td>CH₂CN</td><td>H</td>

<td>br</td><td>F</td><td>CH (Me) CH₂SMe</td><td>Η</td><td>Cl</td><td>br</td><td>F</td><td>CH (Me) CH2SMe</td><td>H</td>

MD 3864 In 2009.03.31

<td>Bl</td><td>Bl</td><td>b!</td><td>and</td><td>B *</td>

<td>Me</td><td>Вт</td><td>F</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>Bi</td><td>F</td><td>Me</td><td>Me</td>

<td>Me</td><td>br</td><td>of</td><td>H</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>Me</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>bt</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>i-Pr</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>ABU</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>ck₂cn</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>C t ^ ^ SMe FMCT</td><td>H</td>

<td>Me</td><td>br</td><td>of</td><td>Me</td><td>Me</td>

<td>Me</td><td>br</td><td>br</td><td>H</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>Me</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>bt</td><td>H</td>

<td>Mo</td><td>br</td><td>br</td><td>Apr</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>ABU</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>ch₂cn</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>CH (Me) CH2SMs</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>br</td><td>br</td><td>Me</td><td>Me</td>

<td>Me</td><td>CF₃</td><td>F</td><td>H</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>Me</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>В</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>Apr</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>ABU</td><td>H</td>

<td>Mo</td><td>CF₃</td><td>F</td><td>CH₂CN</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>CMEF)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>CF₃</td><td>F</td><td>Me</td><td>Me</td>

<td>Me</td><td>CF₃</td><td>of</td><td>H</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>Me</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>bt</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>Apr</td><td>H</td>

<td>Me</td><td>CF₃</td><td>Cl</td><td>ABU</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>CH₂CN</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>CF₃</td><td>of</td><td>Me *</td><td>Me</td>

<td>Me</td><td>CF₃</td><td>br</td><td>H</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>Me</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>bt</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>Apr</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>ABU</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>CH₂CN</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>CF₃</td><td>br</td><td>Me</td><td>Me</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>H</td><td>H</td>

<td>Bl</td><td>ώ</td><td>b!</td><td>bi</td><td>B *</td>

<td>of</td><td>br</td><td>F</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Cl</td><td>br</td><td>F</td><td>Me</td><td>Me</td>

<td>of</td><td>br</td><td>of</td><td>H</td><td>H</td>

<td>of</td><td>br</td><td>Cl</td><td>Me</td><td>H</td>

<td>of</td><td>br</td><td>of</td><td>bt</td><td>H</td>

<td>Cl</td><td>br</td><td>Cl</td><td>Apr</td><td>H</td>

<td>of</td><td>br</td><td>of</td><td>ABU</td><td>H</td>

<td>of</td><td>br</td><td>of</td><td>ch₂cn</td><td>H</td>

<td>Cl</td><td>br</td><td>Cl</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>of</td><td>br</td><td>of</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>of</td><td>br</td><td>of</td><td>Me</td><td>Me</td>

<td>of</td><td>br</td><td>br</td><td>H</td><td>H</td>

<td>of</td><td>br</td><td>br</td><td>Me</td><td>Я</td>

<td>Cl</td><td>br</td><td>br</td><td>bt</td><td>H</td>

<td>of</td><td>br</td><td>br</td><td>Apr</td><td>H</td>

<td>of</td><td>br</td><td>br</td><td>ABU</td><td>H</td>

<td>Cl</td><td>br</td><td>br</td><td>ch₂cn</td><td>H</td>

<td>Cl</td><td>br</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>of</td><td>br</td><td>br</td><td>C (Mc)₂CH₂SMe</td><td>H</td>

<td>of</td><td>br</td><td>br</td><td>Me</td><td>Me</td>

<td>of</td><td>CF3</td><td>F</td><td>H</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>F</td><td>Me</td><td>H</td>

<td>of</td><td>CF₃</td><td>F</td><td>et</td><td>H</td>

<td>of</td><td>CF₃</td><td>F</td><td>Apr</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>F</td><td>ABU</td><td>H</td>

<td>Cl</td><td>CF3</td><td>F</td><td>ch₂cn</td><td>H</td>

<td>Cl</td><td>CF3</td><td>F</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>of</td><td>CF3</td><td>F</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>F</td><td>Me</td><td>Me</td>

<td>Cl</td><td>CF₃</td><td>Cl</td><td>H</td><td>H</td>

<td> □</td><td>CF3</td><td>of</td><td>Me</td><td>H</td>

<td>of</td><td>CF₃</td><td>of</td><td>et</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>of</td><td>Apr</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>of</td><td>ABU</td><td>H</td>

<td>Cl</td><td>CF3</td><td>of</td><td>ch₂cn</td><td>H</td>

<td>of</td><td>CF3</td><td>Cl</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>of</td><td>CF₃</td><td>Cl</td><td>C (Mc) 2CH2SMe</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>of</td><td>Me</td><td>Me</td>

<td>of</td><td>CF₃</td><td>br</td><td>H</td><td>H</td>

<td>Cl</td><td>CT₃</td><td>br</td><td>Me</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>br</td><td>et</td><td>H</td>

<td>of</td><td>CF₃</td><td>br</td><td>Apr</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>br</td><td>ABU</td><td>H</td>

<td>Cl</td><td>CF3</td><td>br</td><td>CH₂CN</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>of</td><td>CF₃</td><td>br</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Cl</td><td>CF₃</td><td>br</td><td>Me</td><td>Me</td>

<td>of</td><td>OCF₂h</td><td>F</td><td>H</td><td>H</td>

MD 3864 In 2009.03.31

<td>к!</td><td></td><td>в!</td><td></td><td></td><td>Bl</td><td>BZ</td><td></td><td>id</td><td></td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>Me</td><td>H</td><td>Cl</td><td>OCF₂h</td><td>F</td><td>Me</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>et</td><td>H</td><td>of</td><td>OCF₂h</td><td>F</td><td>et</td><td>H</td>

<td>Me</td><td>OCF₂H</td><td>F</td><td>i-Pr</td><td>H</td><td>of</td><td>OCF₂h</td><td>E</td><td>i-Pr</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>Z-Bu</td><td>H</td><td>But</td><td>OCF₂h</td><td>F</td><td>i-Bu</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>ch₂cn</td><td>H</td><td>of</td><td>OCF₂h</td><td>F</td><td>ch₂cn</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>CH (Me) CH₂SMe</td><td>H</td><td>Cl</td><td>OCF₂h</td><td>F</td><td>CH (MeX3l2SMe</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>C (Me)₂CH₂SMe</td><td>H</td><td>Cl</td><td>OCF₂h</td><td>F</td><td>С (Ме)₂СН28Ме</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>F</td><td>Me</td><td>Me</td><td>Cl</td><td>OCF₂h</td><td>F</td><td>Me</td><td>Me</td>

<td>Me</td><td>OCF₂h</td><td>of</td><td>H</td><td>H</td><td>of</td><td>OCF₂h</td><td>of</td><td>H</td><td>H</td>

<td>Mo</td><td>OCF₂h</td><td>of</td><td>Me</td><td>H</td><td>Cl</td><td>OCF₂h</td><td>Cl</td><td>Me</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>of</td><td>et</td><td>H</td><td>of</td><td>OCF₂h</td><td>Cl</td><td>et</td><td>H</td>

<td>Mo</td><td>OCF₂h</td><td>of</td><td>i-Pr</td><td>H</td><td>Cl</td><td>OCF₂h</td><td>Cl</td><td>i-Pr</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>of</td><td>t-Bu</td><td>H</td><td>of</td><td>OCF₂h</td><td>Cl</td><td>t-Bu</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>of</td><td>CH₂CN</td><td>H</td><td>of</td><td>OCF₂h</td><td>of</td><td>ch₂cn</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>Cl</td><td>CH (Me) CH₂SMe</td><td>H</td><td>of</td><td>OCF₂h</td><td>Cl</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>of</td><td>C (Me)₂GH₂SMe</td><td>H</td><td>of</td><td>OCF₂h</td><td>of</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>of</td><td>Me</td><td>Me</td><td>of</td><td>OCF₂h</td><td>Cl</td><td>Me</td><td>Me</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>H</td><td>H</td><td>Cl</td><td>OCF₂h</td><td>br</td><td>H</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>Bi</td><td>Me</td><td>H</td><td>of</td><td>OCF₂h</td><td>br</td><td>Me</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>et</td><td>H</td><td>of</td><td>OCF₂h</td><td>br</td><td>et</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>i-Pr</td><td>H</td><td>of</td><td>OCF₂h</td><td>br</td><td>i-Pr</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>t-Bu</td><td>Ή</td><td>of</td><td>OCF₂h</td><td>br</td><td>Z-Bu</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>CH₂CN</td><td>H</td><td>of</td><td>OCF₂h</td><td>br</td><td>CH₂CN</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td><td>of</td><td>OCF₂h</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>C (Me) 2 CH₂SMe</td><td>H</td><td>of</td><td>OCF₂h</td><td>br</td><td>С (Ме)₂СН₂8Ме</td><td>H</td>

<td>Me</td><td>OCF₂h</td><td>br</td><td>Me</td><td>Me</td><td>Cl</td><td>OCF₂h</td><td>br</td><td>Me</td><td>Me</td>

<td>Me</td><td>OCH₂CF3</td><td>F</td><td>H</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>H</td><td>H</td>

<td>Me</td><td>OCH2CF3</td><td>F</td><td>Me</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>Me</td><td>H</td>

<td>Me</td><td>ОСН₂СРз</td><td>F</td><td>et</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>et</td><td>H</td>

<td>Me</td><td>OCH₂CF3</td><td>F</td><td>r-Pr</td><td>H</td><td>Cl</td><td>och₂cf.₃</td><td>F</td><td>i-Pr</td><td>H</td>

<td>Me</td><td>OCH₂CF3</td><td>F</td><td>t-Bu</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>t-Bu</td><td>H</td>

<td>Me</td><td>ОСН₂С? З</td><td>F</td><td>CH₂CN</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>ch₂cn</td><td>H</td>

<td>Me</td><td>ОСН₂СТз</td><td>F</td><td>CH (Me) CH₂SMe</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>ОСН₂СГз</td><td>F</td><td>C (Me)₂CH₂SMe</td><td>H</td><td>of</td><td>och₂cf.₃</td><td>F</td><td>C (Me)₂CH₂SMe</td><td>H</td>

<td>Me</td><td>OCH₂CF₃</td><td>F</td><td>Me</td><td>Me</td><td>Cl</td><td>OCH2CF3</td><td>F</td><td>Me "</td><td>Me</td>

<td>Me</td><td>ОСН₂СРз</td><td>of</td><td>H</td><td>H</td><td>of</td><td>OCH2CF3</td><td>Cl</td><td>H</td><td>H</td>

<td>Me</td><td>OCH2CF3</td><td>of</td><td>Me</td><td>H</td><td>Cl</td><td>OCH2CF3</td><td>Cl</td><td>Me</td><td>H</td>

<td>Me</td><td>OCH₂CF3</td><td>of</td><td>et</td><td>H</td><td>Cl</td><td>OCH2CF3</td><td>of</td><td>et</td><td>H</td>

<td>Me</td><td>OCH2CF3</td><td>Cl</td><td>i-Pr</td><td>H</td><td>of</td><td>OCH2CF3</td><td>of</td><td>iP r</td><td>H</td>

<td>Me</td><td>0СН₂О? З</td><td>of</td><td>t-Bu</td><td>H</td><td>of</td><td>OCH2CF3</td><td>Cl</td><td>t-Bu</td><td>H</td>

<td>Me</td><td>ОСН₂С? З</td><td>of</td><td>CH₂CN</td><td>H</td><td>Cl</td><td>OCH2CF3</td><td>of</td><td>CH₂CN</td><td>H</td>

<td>Me</td><td>OCH2CF3</td><td>of</td><td>CH (Me) CH₂SMe</td><td>H</td><td>of</td><td>OCH2CF3</td><td>of</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>Me</td><td>ОСН₂Сг * з</td><td>of</td><td>C (Me)₂CH₂SMe</td><td>H</td><td> □</td><td>OCH2CF3</td><td>of</td><td>С (Ме)₂СН₂ЗМе</td><td>H</td>

<td>Me</td><td>OCH₂CF3</td><td>of</td><td>Me</td><td>Me</td><td>of</td><td>OCH₂CF₂</td><td>of</td><td>Me</td><td>Me</td>

<td>Me</td><td>OCH₂CF3</td><td>br</td><td>H</td><td>H</td><td>of</td><td>OCH2CF3</td><td>br</td><td>H</td><td>H</td>

<td>Me</td><td>ОСН₂СРз</td><td>br</td><td>Me</td><td>H</td><td>Cl</td><td>OCH2CF3</td><td>br</td><td>Me</td><td>H</td>

MD 3864 In 2009.03.31

<td>В?</td><td></td><td>Bi</td><td></td><td>Bl</td><td></td><td>Bl</td><td>Bi</td><td>b £</td>

<td>OCH2CF3</td><td>br</td><td>et</td><td>h</td><td>of</td><td>OCH₂CF₃</td><td>br</td><td>et</td><td>h</td>

<td>OCH2CF3</td><td>br</td><td>i-Pr</td><td>H</td><td>of</td><td>OCH₂CP₃</td><td>br</td><td>i-Pr</td><td>H</td>

<td>OCH2CF3</td><td>br</td><td>t-Bu</td><td>H</td><td>of</td><td>OCH2CF3</td><td>br</td><td>i-Bu</td><td>H</td>

<td>OCH2CF3</td><td>br</td><td>2 CN</td><td>H</td><td>of</td><td>OCH2CF3</td><td>br</td><td>CH₂CN</td><td>H</td>

<td>OCH2CF3</td><td>br</td><td>СЩМе ^ ЗМе</td><td>H</td><td>Cl</td><td>OCH2CF3</td><td>br</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td> 0012^3</td><td>br</td><td>C (Me)₂CH₂SMe</td><td>H</td><td>of</td><td>OCH2CF3</td><td>br</td><td>C (Me)₂CH2SMe</td><td>H</td>

<td>OCH2CF3</td><td>br</td><td>Me</td><td>Me</td><td>Cl</td><td>OCH2CF3</td><td>br</td><td>Me</td><td>Me</td>

<td>OCF3</td><td>F</td><td>H</td><td>H</td><td>of</td><td>OCF3</td><td>F</td><td>H</td><td>H</td>

<td>OCF3</td><td>F</td><td>Me</td><td>H</td><td>of</td><td>OCF3</td><td>F</td><td>Me</td><td>H</td>

<td>OCF3</td><td>F</td><td>et</td><td>H</td><td>Cl</td><td>OCF3</td><td>F</td><td>et</td><td>H</td>

<td>OCF3</td><td>F</td><td>i-Pr</td><td>H</td><td>of</td><td>OCF3</td><td>F</td><td>i-Pr</td><td>H</td>

<td>OCF3</td><td>F</td><td>i-Bu</td><td>H</td><td>of</td><td>OCF3</td><td>F</td><td>i-Bu</td><td>H</td>

<td>OCF3</td><td>F</td><td>ch₂cn</td><td>H</td><td>Cl</td><td>OCF3</td><td>F</td><td>ch₂cn</td><td>H</td>

<td>OCF3</td><td>F</td><td>CH (Me) CH2SMe</td><td>H</td><td>Cl</td><td>OCF3</td><td>F</td><td>CH (Me) CH2SMe</td><td>H</td>

<td>OCF3</td><td>F</td><td>C (Me) 2CH2SMe</td><td>H</td><td>of</td><td>OCF3</td><td>F</td><td>C (Me)₂CH2SMe</td><td>H</td>

<td>OCF3</td><td>F</td><td>Me</td><td>Me</td><td>of</td><td>OCF3</td><td>F</td><td>Me</td><td>Me</td>

<td>OCF3</td><td>of</td><td>H</td><td>H</td><td>Cl</td><td>OCF3</td><td>of</td><td>H</td><td>H</td>

<td>OCF3</td><td>of</td><td>Me</td><td>H</td><td>Cl</td><td>OCF3</td><td>of</td><td>Me</td><td>H</td>

<td>0CF3</td><td>of</td><td>et</td><td>H</td><td>Cl</td><td>OCF3</td><td>Cl</td><td>et</td><td>H</td>

<td>OCF3</td><td>of</td><td>i-Pr</td><td>H</td><td>Cl</td><td>OCF3</td><td>Cl</td><td>i-Pr</td><td>H</td>

<td>OCF3</td><td>of</td><td>i-Bu</td><td>H</td><td>Cl</td><td>OCF3</td><td>Cl</td><td>i-Bu</td><td>H</td>

<td>OCF₃</td><td>of</td><td>ch₂cn</td><td>H</td><td>Cl</td><td>OCF3</td><td>of</td><td>CH₂CN</td><td>H</td>

<td>OCF3</td><td>of</td><td>CH (Me) CH2SMe</td><td>H</td><td>Cl</td><td>OCF3</td><td>Cl</td><td>CH (Me) CH₂SMe</td><td>H</td>

<td>OCF3</td><td>Cl</td><td>C (Me) 2CH2SMe</td><td>H</td><td>of</td><td>OCF₃</td><td>Cl</td><td>C (Me) 2 CH₂SMe</td><td>H</td>

<td>OCF3</td><td>of</td><td>Me</td><td>Me</td><td>Cl</td><td>OCF3</td><td>Cl</td><td>Me</td><td>Me</td>

<td>OCF3</td><td>br</td><td>H</td><td>H</td><td>Cl</td><td>OCF3</td><td>br</td><td>H</td><td>H</td>

<td>OCF3</td><td>br</td><td>Me</td><td>H</td><td>Cl</td><td>OCF3</td><td>br</td><td>Me</td><td>H</td>

<td>OCF3</td><td>br</td><td>et</td><td>H</td><td>Cl</td><td>OCF3</td><td>br</td><td>et</td><td>H</td>

<td>OCF₃</td><td>br</td><td>i-Pr</td><td>H</td><td>Cl</td><td>OCF3</td><td>br</td><td>i-Pr</td><td>H</td>

<td>OCF₃</td><td>br</td><td>i-Bu</td><td>H</td><td>Cl</td><td>OCF3</td><td>br</td><td>t-Bu</td><td>H</td>

<td>OCF3</td><td>br</td><td>ch₂cn</td><td>Ή</td><td>Cl</td><td>OCF3</td><td>br</td><td>CH₂CN</td><td>H</td>

<td>OCF3</td><td>br</td><td>CH (Me) CH2SMe</td><td>H</td><td>of</td><td>OCF3</td><td>br</td><td>CH (Me) CH2SMe</td><td>H</td>

<td>OCF₃</td><td>br</td><td>CfMe ^ Q ^ SMe</td><td>H</td><td>Cl</td><td>OCF3</td><td>br</td><td>C (Me)₂CH2SMe</td><td>H</td>

<td>OCF₃</td><td>br</td><td>Me</td><td>Me</td><td>of</td><td>OCF3</td><td>br</td><td>Me</td><td>Me</td>

Table 2

MD 3864 F12009.03.31

<img file="MD3864B2_D0032.tif" />

<td>в2</td><td>В *</td><td>bi</td><td>B *</td><td>Bl</td><td> £</td><td> £</td><td>в1</td><td>B $</td>

<td>CF₃</td><td>а</td><td>Мс</td><td>F</td><td>Me</td><td>cf.₃</td><td>а</td><td>Ме</td><td>а</td>

<td>GF₃</td><td>а</td><td>Me</td><td>F</td><td>а</td><td>CF3</td><td>а</td><td>Me</td><td>а</td>

<td>CF₃</td><td>а</td><td>Me</td><td>F</td><td>br</td><td>CF₃</td><td>а</td><td>Me</td><td>а</td>

<td>а</td><td>а</td><td>Me</td><td>F</td><td>Me</td><td>а</td><td>а</td><td>Me</td><td>а</td>

<td>а</td><td>а</td><td>Me</td><td>F</td><td>а</td><td>а</td><td>а</td><td>Me</td><td>а</td>

<td>а</td><td>а</td><td>Me</td><td>F</td><td>br</td><td>а</td><td>а</td><td>Me</td><td>а</td>

<td>Вт</td><td>а</td><td>Me</td><td>F</td><td>Me</td><td>br</td><td>а</td><td>Me</td><td>а</td>

<td>Вг</td><td>а</td><td>Me</td><td>F</td><td>а</td><td>br</td><td>а</td><td>Me</td><td>а</td>

<td>Вт</td><td>а</td><td>Me</td><td>F</td><td>br</td><td>br</td><td>а</td><td>Me</td><td>а</td>

<td>CF₃</td><td>а</td><td>i-Pr</td><td>F</td><td>Me</td><td>cf.₃</td><td>а</td><td>i-Pr</td><td>а</td>

<td>CF3</td><td>а</td><td>i-Pr</td><td>F</td><td>а</td><td>cf.₃</td><td>а</td><td>i-Pr</td><td>а</td>

<td>CF3</td><td>а</td><td>i-Pr</td><td>F</td><td>br</td><td>CF3</td><td>а</td><td>i-Pr</td><td>а</td>

<td>а</td><td>а</td><td>i-Pr</td><td>F</td><td>Me</td><td>а</td><td>а</td><td>i-Pr</td><td>а</td>

<td>а</td><td>а</td><td>i-Pr</td><td>F</td><td>Cl</td><td>а</td><td>а</td><td>i-Pr</td><td>а</td>

<td>а</td><td>а</td><td>i-Pr</td><td>F</td><td>br</td><td>а</td><td>а</td><td>i-Pr</td><td>а</td>

<td>Вт</td><td>а</td><td>i-Pr</td><td>F</td><td>Me</td><td>br</td><td>а</td><td>i-Pr</td><td>а</td>

<td>Вг</td><td>а</td><td>i-Pr</td><td>F</td><td>а</td><td>br</td><td>а</td><td>i-Pr</td><td>а</td>

<td>Вг</td><td>а</td><td>i-Pr</td><td>F</td><td>br</td><td>br</td><td>а</td><td>i-Pr</td><td>а</td>

Table 3

<img file="MD3864B2_D0033.tif" />

MD 3864 In 2009.03.31

<td>Bl</td><td>Bl</td><td></td><td>Ki</td><td>RZ</td><td>к!</td><td>and</td><td>Bl</td><td>Kl</td><td>RZ</td>

<td>Me</td><td>cf.₃</td><td>F</td><td>Me</td><td>F</td><td>Me</td><td>CF₃</td><td>of</td><td>Me</td><td>Cl</td>

<td>of</td><td>СУ3</td><td>F</td><td>Me</td><td>F</td><td>of</td><td>CF₃</td><td>of</td><td>Me</td><td>of</td>

<td>Вт</td><td>σ₃</td><td>F</td><td>Me</td><td>F</td><td>br</td><td>CF3</td><td>of</td><td>Me</td><td>of</td>

<td>ц!</td><td></td><td></td><td>Bl</td><td>b2</td><td>Bl</td><td>RZ</td><td>ώ</td><td>id</td><td>RZ</td>

<td>Me</td><td>of</td><td>F</td><td>Me</td><td>F</td><td>Me</td><td>of</td><td>of</td><td>Me</td><td>of</td>

<td>of</td><td>of</td><td>F</td><td>Me</td><td>F</td><td>of</td><td>of</td><td>of</td><td>Me</td><td>Cl</td>

<td>br</td><td>of</td><td>F</td><td>Me</td><td>F</td><td>br</td><td>of</td><td>of</td><td>Me</td><td>Cl</td>

<td>Me</td><td>br</td><td>F</td><td>Me</td><td>F</td><td>Me</td><td>br</td><td>of</td><td>Me</td><td>of</td>

<td>of</td><td>br</td><td>F</td><td>Me</td><td>F</td><td>of</td><td>br</td><td>of</td><td>Me</td><td>of</td>

<td>br</td><td>br</td><td>F</td><td>Me</td><td>F '</td><td>br</td><td>br</td><td>of</td><td>Me</td><td>of</td>

<td>Me</td><td>CF₃</td><td>F</td><td>BPR</td><td>F</td><td>Me</td><td>CF₃</td><td>of</td><td>/ Pr</td><td>of</td>

<td>of</td><td>CP₃</td><td>F</td><td>i-Pr</td><td>F</td><td>of</td><td>CF₃</td><td>of</td><td>i-Pr</td><td>of</td>

<td>br</td><td></td><td>F</td><td>/ Pr</td><td>F</td><td>br</td><td>CF₃</td><td>of</td><td>/ Pr</td><td>of</td>

<td>Me</td><td>of</td><td>F</td><td>i-Pr</td><td>F</td><td>Me</td><td>of</td><td>of</td><td>i-Pr</td><td>of</td>

<td>of</td><td>of</td><td>F</td><td>LPR</td><td>F</td><td>of</td><td>of</td><td>Q</td><td>i-Pr</td><td>of</td>

<td>br</td><td>of</td><td>F</td><td>/ Pr</td><td>F</td><td>br</td><td>of</td><td>of</td><td>/ Pr</td><td>of</td>

<td>Mo</td><td>br</td><td>F</td><td>i-Pr</td><td>F</td><td>Me</td><td>br</td><td>of</td><td>/ Pr</td><td>of</td>

<td>of</td><td>br</td><td>F</td><td>i-Pr</td><td>F</td><td>Cl</td><td>br</td><td>of</td><td>/ Pr</td><td>of</td>

<td>br</td><td>br</td><td>F</td><td>i-Pr</td><td>F</td><td>br</td><td>br</td><td>of</td><td>/ Pr</td><td>of</td>

The form has a / u lity

The compounds of the present invention will generally be used as a formulation or composition with a carrier suitable for agronomic or non-agro-nomic use containing at least one of the liquid diluents, a solid diluent or a surfactant. The ingredients of the formulation or composition are selected to correspond to the physical properties of the active ingredient, the mode of application and environmental factors such as soil type, humidity and temperature. Useful formulations include liquids, such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspensions) and the like, which can optionally be thickened in gels. Useful formulations also include solid substances, such as powders, powders, granules, tablets, pills, films and the like, which may be dispersible in water ("wettable") or water soluble. The active ingredient can be (micro) encapsulated and subsequently formed into a suspension or solid formulation; alternatively the total formulation of the active ingredient may be capsulated (or "coated"). Capsulation can control or delay separation of the active ingredient. The spray formulations can be dissolved in convenient environments and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further preparation.

The formulations will typically contain effective quantities of active ingredient, diluent and surfactant taken in the indicated quantities, which together constitute up to 100% by mass.

Percentage by mass

<td></td><td>Active ingredient</td><td>thinner</td><td>Surfactant substance</td>

<td>Water-soluble, water-soluble powders, tablets and granules</td><td> 5...90</td><td> 0...94</td><td> 1...15</td>

<td>Suspensions, emulsions (including emulsifiable concentrates)</td><td> 5...50</td><td> 40...95</td><td> 0...15</td>

<td>powders</td><td> 1...25</td><td> 70...99</td><td> 0...5</td>

<td>Granules and pills</td><td> 0,01...99</td><td> 5...99,99</td><td> 0...15</td>

<td>High composites resin stents</td><td> 90...99</td><td> 0...10</td><td> 0...2</td>

Typical solid diluents are described in Watkins et al. Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, inserts surfactants and recommended uses. All formulations may contain minor amounts of additions to reduce foaming, sintering, corrosion, microbiological growth, etc., or thickeners to increase viscosity.

Surfactant substrates include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, sorbitan fatty acid esters, polyethoxysilaphs, dialkylsulfosuccinates, alkylsulfaphs, alkylbenzenesulfonyls, organosilicones, N, N-dialalkylatedes, condensates, lignins,

MD 3864 Fl 2009.03.31 of polyoxyethylene / polyoxypropylene. Solid diluents include, for example, clays, such as bentonite, montmorillonite, atapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, NM, Ndimethylformamide, dimethylsulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, line oil, castor, linseed, porcinium, tungsten, cottonseed, soybean, raspberry and coconut, fatty acid esters, ketones, such as 4-hydroxy-4-methyl-2-pentanone, and alcohols, such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.

The solutions, which include emulsifiable concentrates, can be prepared by simple mixing of the ingredients. The powders and powders can be prepared by blending and usually ground, such as in a hammer mill or a fluidized mill. Suspensions are usually prepared by wet grinding; see, for example, US 3,060 084. Granules and pills can be prepared by spraying active material on preformed granular carriers or by agglomeration techniques (see Browning .. Agglomeration.) Chemical Engineering, December 4, 1967, pp. 147-148, Perry's Chemical Engineer's Handbook, 4th ed. -a, McGraw-Hill, New York, 1963, pages 8-57 and PCT Publication WO 91/13546). The pills can be prepared as described in US 4,172,714. Water soluble and water dispersible granules may be prepared as described in US 4,144,050, US 3 920 442 and DE 3 246 493. Tablets may be prepared as described in US 5 280 587, US 5 232 701 and US 5 208 030. Films can be prepared as described in GB 2 095 558 and US 3 299 566.

For more information on the formulation field, see TS Woods, "The Formulator's Toolbox-Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, ed. T. Brooks and TR Roberts, Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also US 3 235 361, col. 6, row 43 of Col. 7, row 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166,167, and 169-182; US 2 891 855, col. 3, row 66 et al. 5, row 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, ed. 8th, Blackwell Scientific Publications, Oxford, 1989.

In the following examples all percentages are table and all solutions are prepared in traditional ways. The numbers of the compounds refer to the compounds in Index Table A.

Example A

65,0%

2,0%

Wettable powder

Compound 1 dodecylphenol ether polyethylene glycol

<td>sodium lignin sulphonate silicoaluminate sodium montmorillonite (calcined)</td><td colspan="2"> 4,0% 6,0% 23,0%</td>

<td>Granule Compound 1</td><td>Example В</td><td> 100%</td>

<td>granules of atapulgite (material</td><td>weak volatile, 0.71 / 0.30 mm; USS No.</td><td> 90,0%</td>

<td>25-50 sites) Extruded pill Compound 1</td><td>Example C</td><td> 25,0%</td>

<td>crude sodium sulfate</td><td></td><td> 10,0%</td>

<td>sodium ligninsulphate</td><td></td><td> 5,0%</td>

<td>sodium alkylnaphthalenesulfonate</td><td></td><td> 1,0%</td>

<td>magnesium / calcium bentonite</td><td></td><td> 59,0%</td>

<td>Emulsifiable concentrate Compound 1</td><td>Example D</td><td> 20,0%</td>

<td>mixture of soluble sulphonates in</td><td>polyoxyethylene oil and ethers</td><td></td>

<td>isophorone</td><td></td><td> 10,0% 70,0%</td>

<td>Granulate Compound 1</td><td>Example E</td><td> 0,5%</td>

<td>cellulose</td><td></td><td> 2,55</td>

<td>lactose</td><td></td><td> 4,0%</td>

<td>cornflour</td><td></td><td> 93,0%.</td>

MD 3864 In 2009.03.31

The compounds of the present invention are characterized by the residual characters of favorable metabolism and / or soil and manifest activity of combating a spectrum of agronomic and non-agronomic invertebrates. The compounds of the present invention are also characterized by favorable foliar systemicity and / or applied by the soil in plants, exercising translocation to protect the foliage and other parts of plants that have not directly contacted the insecticidal compositions containing the compounds present. (In the context of this description "fighting invertebrate fish" means inhibition of the development of invertebrate fish (including mortality) which causes a reduction in feed or other damage or damage caused by fish; related expressions are similarly defined.) As described, the term "Invertebrate fish" includes arthropods, gastropods and nematodes of economic importance as well as fish. The term "arthropod" includes insects, mites, spiders, scorpions, chilopods, myrrhidae, babysitters (mops) and scolopendrons. The term "gastropod" includes snails, snails and other stylomatophores. The term "nematode" includes all helminths, such as phytophagous limbs and nematodes, trematodes, acanthocephalics and parasitic worms in the form of ribbons (Cestodes). Those skilled in the art will recognize that not all compounds are equally effective against fish. The compounds of the present invention manifest activity against economically important agronomic and non-agronomic fishes. The term "agronomic" refers to the production of field crops, such as for food and fiber, and includes the growth of cereal crops (eg, wheat, oats, barley, rye, rice, corn), soybean crops, vegetable crops (de eg, green salad, cabbage, tomatoes, beans), potatoes, sweet potatoes, poems, cotton and fruits (eg, seed poems, peach fruits and citrus fruits). The term "non-agronomic" refers to other fruit plants (eg forest, greenhouse, nursery or ornamental plants that are not grown in the field), lawns (commercial, golf, residential, recreational, etc.), wood products, the birth of humans and animals, commercial and domestic structure, household, and fish or applications of stored products. Due to the spectrum of control of invertebrate fish and the economic importance, the protection (against damage or damage caused by invertebrate fish) of bum-bac, corn, soybean, rice, vegetable, potato, sweet potato, fruit and fruit crops Examples of embodiment of the invention are preferred by controlling invertebrate fish. Agronomic or non-agronomic fish include larvae of the order Lepi-dopter, such as owls, butterflies, butterflies, quail, and the nocturnal butterfly family Noctuidae (eg, Spodoptera fugipedra JE Smith), buha-mica (Spodoptera exigua Hubner), butterfly ipsilon (Agrotis ipsilon Hufnagel), buha-cabbage (Trichoplusia ni Hubner), omida-tobacco (Heliothis virescens Fabricius); minions, moles, miners, spiders, worms and worms that skeletonize leaves in the Piralidae family (eg, butterflies (Ostrinia nubilalis Hubner), Walker butterflies (Amyelois transitella), (Crambus calensinosellus), (Herpetogramma licarsisalis Walker)); tortricides, cigarettes, seed worms and fruit worms in the Tortricidae family (eg, apple worms (Cydia pomonella Linnaeus), pyrotechnics (Endopiza viteana Clemens), omida-oriental-peach (Grapholita molesta Busck) and many more other economically important lepidoptera (eg moth-cabbage (Plutella xylostella Lin-naeus), worm-pink-albacore (Pectinophora gossypiella Saunders), hawthorn-oak (Lumantria disappear Linnaeus)); adult nymphs and insects of the Blatod order, including beetles from the Blatelidae and Blatidae families (eg, black-cockroach (Blatta orientalis Linnaeus), Asian-cockroach (Blatella asahinai Mizukubo), German-cockroach) Linnaeus), the beetle (Supella longipalpa Fabricius), the American beetle (Periplaneta americana Linnaeus), the beetle-brown (Periplaneta brunnea Burmeister), the beetle-de-Madeira (Leucophaea maderae Fabricius); adult larvae and insects feeding on leaves of the order of Coleoptera, including ladybugs in the families of Antribidae, Bruchidae and Curculionidae (eg, cottonseed (Anthonomus grandis Boheman), Kestrel-rice-water (Lissorhopus) -gra (Sitophilus granarius Linnaeus), rice bran (Sitophilus oryzae Linnaeus); ground fleas, beetle-mites, Colorado beetles, potato fleas and miners in the Chrysomelid family (eg, the cockroach-de-colorado) (Leptinotarsa ​​decemlineata Say), the western worm of maize root (Diabrotica) virgifera LeConte); beetles and other cockroaches of the Scarabaeidae family (eg "Japanese beetle (Popillia japonica Newman) and European beetle (Rhizotrogus majalis Razo-umowsky)); the beetles of the skin of the Dermestide family; wire worms from the family of Elaterides; bark beetles from the Scolithite family and cockroaches from the Tenebrionid family. In addition, agronomic and non-agronomic fish include: adult insects and larvae of the order of Dermaptera, including the earworms of the Forficulidae family (eg, the common earworm (Forficula auricularia Linnaeus), the black-eared eagle (Chelisoches morio Fabricius); adult insects and nymphs in the orders of Hemiptera and Homoptera, such as: herbs from the family of Miridas, cicadas from the family of Cicadas, cicadas (eg, Empoasca spp.) from the family of Cicadelides, cicadas from the families of Fulgoroids and Delfacids, chicory-bites from the family of Membracides, psyllids from the family of Psilids, aleirod family Aleirodids, aphids in the family of aphids, phylloxera in the family of phylloxerids, lice in the Pseudococcid family, lice in the Coccid family, Diaspidids and Margarodids, Fingid family breams, Pentatomid family bream cereals, North American wheat bean bites (eg, Blissus spp.) And other seed bites from the Ligaeididae family, Bleeding bean from the Cormorant family , and the red-and-red-and-red-cotton-bunnies of the Pirrocorid family. Also included as agronomic and non-agronomic are adult insects and larvae in the order of mites (mites), such as: common spiders of the Tetranicid family (eg, spider-red-tree-spider (Panonychus ulmi Koch)), spider two-spotted (Tetranychus urticae Koch), McDaniel tick (Tetranychus mcdanieli

MD 3864 In 2009.03.31

McGregor), flat claws from the Tenuipalpid family (eg, citrus cleaver (Brevipalpus lewisi McGregor), vine clippers and claw clippers from the family of Eriophidae and other mites that feed on leaves and mites important to human health and to humans. clippers from the Epidermoprid family, eels from the Demodicide family, wheat ticks from the Glycifagidae family, ticks from the Ixodide family (e.g., deer (Ixode scapularis Say)), Australian tick (Ixodes holocyclus Neumann), dog-tick {Dermacentor variabilis Say), tick-tick {Ambyomma americanum and Linna) - of laughter from the families of Psoroptids, Piemotides and Sarcoptids; adult and immature insects on the order of Orthoptera, including brambles, locusts and crickets (eg, buggies (e.g., Melanoplus sanguinipes Fabricius, M.) differentialis Thomas), American locusts (eg, American schistocerca Drury), wild locust {Schistocerca gregaria Forskal), traveling locust {Locusta migratoria Linnaeus), shrubby locust {Zonocerus spp.), gravel homemade (Acheta domestricus Linnaeus), coropișnițele (Gryllotalpa spp.)); adult and immature insects on the order of Dipteres, including miners, moths, drosophile flies (Tefritids), Swedish-flies (eg, Oscinellafrit Linnaeus), ground-larvae-apods, house-flies (e.g. ., Musca domestica Linnaeus), house-flies (eg, Fannia canicularis Linnaeus, F. Stein femoralis), common flies (e.g., Stomoxys calcitrans Linnaeus), autumn flies, blue flies (e.g., Chrysomya spp., Phormia spp.) and other flying flies, horsehair (e.g. , Tabanus spp.), Narrow-gastric larvae (eg, Gastrophilus spp., Oestrus spp.), Calf strains (e.g., Hypoderma spp.), Reindeer (e.g., Chrysops spp.) .), ticks (e.g., Melophagus ovinus Linnaeus) and other Brachychids, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), Molluscs (eg, Prosimulium spp., Simulium spp.), Biting-flies, mosquitoes, sciarids and other Nematocere; adult and immature insects of the Tisanoptera, including tobacco thrips {Thrips tabaci Lindeman), wheat thrips {Frankliniella spp.) and other leaf-feeding tripods; harmful insects in the order of Hymenopterans, including ants (eg, red-throated-ant-Pennsylvania {Camponotus ferrugineus Fabricius), red-throated-ferns of Pennsylvania {Camponotus pennsylvanicus De Geer), house ant {Monomorium) {Monomorium) , fornicavasmania {Wasmannia auropunctata Roger), ant-solenopsis {Solenopsis geminata Fabricius), fumica-red-alui-Richter {Solenopis invicta Buren), ant-argentinian {Iridomyrmex humilis Mayr), ant {Paratrechina longicornis Latreille), meadow ant (Tetramorium caespitum Linnaeus), American ant (Lasius alienus Forster), ant {Tapinoma sessde Say)), bees (including bee-bees), wasps, buzzards and wasps {saws { Neodiprion spp., Cephus spp.); harmful insects in the order of Isoptera, including termites {Reticulitermes flavipes Kollar), {Reticulitermes hesperus Banks), (Coptotermes formosanus Shiraki), {Incisitermes immigrans Snyder) and other isotopes of economic importance; harmful insects in the order of the Tizanura, such as {Lepisma saccharina Linnaeus) and (Thermobia domestica Packard); harmful insects in the order of Malophages, including head lice {Pediculus humanus capitis De Geer), body lice {Pediculus humanus humanus Linnaeus), malophagus {Menacanthus stramineus Nitszch), dog lice {Trichoder canis) , lice {Goniocotes gallinae De Geer), ticks {Bovicola ovis Schrank), lice {Haematopinus eurysternus Nitzsch), long-nosed-horned-lice {Linognathus vituli Linnaeus) and other parasitic lice that are blood-sucking and ruminant-attacking humans and animals; harmful insects in the order of Siphonopterans, including rat fleas {Xenopsylla cheopis Rothschild), cat fleas {Ctenocephalides felis Bouche), dog fleas {Ctenocephalides canis Curtis), chicken fleas {Ceratrankllus gallina) , the weasel {Echidnophaga gallinacea Westwood), fleas {Pulex irritans Linnaeus) and other lice that affect mammals and birds. Invertebrate fish additionally included: spiders of the order Araneae, such as the spider {Loxosceles reclusa Gertsch &amp; Mulaik) and the spider-weaver-black {Latrodectus mactans Fabricius), and the centipedes of the order Scutigeromorphs, such as the lizard { -naeus). The compounds of the present invention also possess action on members of the classes of Nematodes, Cestodes, Trematodes and Acantocephalics, including members of economic importance in the orders of Strongilides, Ascaridides, Oxiurides, Rabbits, Spirurids and Enoplids, such as, but not limited to, fish. of economic importance (ie, the gall-nematodes of the genus Meloidogyne, the harmful nematodes of the genus Pratylenchus, the nematodes of the genus Trichodorus, etc.) and fish that affect the health of humans and animals (ie all trematodes, ribbon worms and cylindrical worms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplota in horses; Fadciola hepatica Linnaeus in ruminants, etc.).

The compounds of the invention possess particular high activity against fish of the order Lipidoptera (eg, Alabama argillacea Hubner (buha-cotton-American), Archips argyrospila Walker (butterfly-omit-apom), A. rosana Linnaeus (European caterpillar), and other species Archips, Chilo suppressalis Walker (paratora), Cnaphalocrosis medinalis Guenee (buha-rice), Crambus caliginosellus Clemens (butterfly moth), Crambus teterrellus Zincken (butterfly), Cydia pomonier Lineae apples), Earias insulana Boisduval (omida-cuspini), Earias vitella Fabricius (worm-spotted), Helicoverpa armigera Hubner (American worm), Helicoverpa Zea Boddie (cotton-wool), Heliothis virescens Fabricius (tobacco moth), Herpetogramma licarsisalis Walker (butterfly), Lobesia botrana Denis &amp; Schiffermuller (pirala-vines), Pectinophora gossypiella Saunders (worm-pink-cotton-worm), Phyllocnistis citrella Strainton (moth-moth) citrus fruits), Pieris brassicae Linnaeus (white-cabbage), Pieris rapae Linnaeus (white-cabbage), Plutella xylostella Linnaeus (moth-cabbage), Spodoptera exigua Hubner (buha-mica), Spodoptera litura Fabricius (butterfly, omida-clusters), Spodoptera

MD 3864 Fl 2009.03.31 frugiperda JE Smith (buha-grass), Trihoplusia ni Hubner (buha ni) and Tuta absolutely Meyrick (miner-tomato). The compounds of the invention also possess о important commercial activity on the members of the Homoptera order, including: Acyrthisiphon pisum Harris (aphea peas), Aphis craccivora Koch (lice-black-alsfecle), Aphis fabae Scopoli (lice-black-beet), Aphis gossypii Glover (lice-bum-bac, lice-cucumber, lice-cucumber) De Geer (the green-lion's-lice), Aphis spiraecola Patch (lice-avavelet), Aulacorthum solani Kaltenbach (lice-lice), Chaetosiphon fragaefolii Cockerell (lice-louse), Diuraphis noxia Kurdjumov / Muchvilko-Russia ) Dysaphis plantaginea Paaserini (green-rose-lice), Eriosoma lanigerum Hausmann (woolly lice), Hyalopterus prunes Geoffroy (prairie-lice), Lipaphis erysimi Kaltenbach (louse), Metopolophieal cerd Walker , Macrosipum euphorbiae Thomas (potato-leaf-lice), Myzus persicae Sulzer (potato-and-peach-leaf lice, green-peach lice), Nasonovia ribisnigri Mosley (chick-pea) -frunzelor-of-lettuce), Pemphigus spp. (Root lice and tuber lice), Rhopalosiphum maidis Fitch (maize-leaf lice), Rhopalosiphum padi Linnaeus (lice), Schizaphis graminum Rondani (bird-lice) Fabricius (wheat lice), Therioaphis maculata Buckton (lucerne-lice), Toxoptera aurer Bayer de Fonscolombe (flea-black-cherry-broom), and Toxoptera citricida Kir-kaldy (citrus lice); Adelges spp. (Adelgide); Phylloxera devastatrix Per-gande (phylloxera), Bemisia tabaci Gennadius (tobacco aleroidide, beaten aleroidide), Bemisia argentifolii Bellows &amp; Perring (white-magnolia), Dialeurodes citri Ashmead (white-citrus) and Trialeurwood vaporum the conservatory); Empoasca fabae Harris (potato-chicory), Laodelphax striatellus Fallen (small-coffee-chicory), Macrolestes quadrilineatus Forbes (turkey-eyed-chicory), Nephotettix ciniceps Uhler (green-cicada), Nephotettix nigropictus Stalata (cicada) Stal lugens, Peregrinus maidis Ashmead, Sogatella furcifera Horvath, Sogatodes orizicola Muir, Typhlocyba pomaria McAtee (apple coriander), Erythroneoura spp. (Succories-vine); Magicidada septendecim Linnaeus (17-year-old chicory); Icerya purchasi Maskell (turtle-shaped-lice-of-Australia), Quadraspidiotus perniciosus Comstock (San-Jose-lice); Pianococcus citri Risso (lice-flour-vines); Pseudococcus spp. (Another complex of turtle lice); Cacopsylla pyricola Foerster (melicea-hair-flea), Ashmead Trioza diospyri (puricelemelifer-al-hurma). These compounds also possess action on members of the Hemiptera order, including: Ac rosternum hilare Say (ploshite-scutar), Anasa tristis De Geer (rhombus-ploidy), Blissus leucopterus Say (ploshite-pea-mant), Corythuca gossypii Fabricius (red-bellied plovers), Dysdercus suturellus Her-rich-Schaffer (red-plumed-cotton-blossom), Euchistus servus Say (brown-squirrel-brown), Euchistus variolarius Palisot de Beauvois (white-squirrel-squirrel) stain), Graptosthetus spp. (seed-bedding complex), Leptoglossus corculus Say (pine seed-bedding), Lygus lineolaris Palisot de Beauvois (meadow-meadow), Nezara viridula Linnaeus, Oebalus pugnax Fabricius (meadow- rice), Oncopeltus fasciatus Dallas (Dallas plosnita), Pseudatomoscelis seriatus Reuter (ploșnița-taun). Other orders of insect wiped out by the compounds of the invention include the order of the Tyrannoptera (eg, Frankliniella occi-dentalis Pergande (thrips-flowers), Scirthothrips citri Moulton (thrips-citris), Sericothrips variabilis Beach (thrips-soybeans), and Thrips tabaci Lindeman (thrips-onion); and the order of Coleoptera (eg, Leptinotarsa ​​decemlineata Say (Colorado-cockroach), Epilachna varivestis Mulsant (Mexican-a-boar) and worms of the genus Agriotes, Athous or Limonius).

The compounds of the present invention may also be mixed with one or more ahi compounds or biologically active agents, including insecticides, nematocides, bactericides, acaricides, regulators! growth enhancers, such as rooting stimulants, chemosterilizers, semi-chemical repellents, attractants, pheromones, entomopathogenic food stimulants, viruses or fungi to form a multicomponent pesticide that gives an equal broad spectrum of agronomic and non-agronomic utility. Thus, the present invention also relates to the о composition which confines о the biologically effective amount of a compound of formula 1 and о the effective amount of at least one additional and additional biologically active compound or agent may contain at least one surfactant, a solid diluent or a liquid diluent. Examples of these biologically active compounds or agents with which the compounds of the present invention can be formulated are: insecticides, such as abamectin, azadirectin, azinfos-methyl, bifentril, bifenazate, bistrifluron, buprofezin, carbofuran, chlorophenapyr, chlorofluazuron, chlorpyrifos, chlorpyrifos-methyl, cromaphenosine, kryphotothine, kryphotothrine, , ciromazine, deltamethrin, diafentiuron, diazinone, diflubenzuron, dimethoate, dinotefuran, diophenolane, emamectin, endosulfan, sphenvalerate, etiprol, phenoticab, phenoxycarb, fenpropatrin, fenvalerate, fipronil, flonicamide, flucitrinate, tau-fluvalinate, flufenerime (UR-50701), flufenoxuron, ga-ma-calotrine, halofenoside, hexaflumuron, imidacloprid, indoxacarbon, metophene, isofe, malofluoride, isofe , metidation, methyl-mil, metoprene, methoxychloro, methoxyphenoside, metoflutrine, monochrotrophos, methoxyphenozide, novaluron, novilflumuron (XDE-007), oxamyl, paration, paration-methyl, permethrin, bore, fozalon, phosphometra, phosphamidone, pyrimide carbene, profenofos, proflutrine, protrifenbut, pimetrozine, pyridyl, pyripro-xiphen, rotenone, SI812 (Valent) spinozad, spiromezifene (BSN 2060), sulph-rofoside, teflufen, teflufen, teflufen, teflufen. tetrachlorvinphos, thia-chlorprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpirad, tralometrine, trichlorfonone and triflumuron; fungicides, such as acibenzolar, Smetyl, azoxistrobin, benalazi-M, bentia-valicarb, benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulphate), boscalide, bromuconazole, butiobate, carpropamide, captafol, captafol, captafol, captafol

MD 3864 Fl 2009.03.31 chloroebil, chlorothalonil, chloro-trimazole, copper oxychloride, copper salts, cimoxanil, ciazofamide, ciflufenamide, ciproconazole, ciprodinil, diclocimeter, dichlomezine, dichloran, de-phenoconazol, dimoxoniconazole, dimoxoniconazole, dim M, dodine, edifenphos, epoxiconazole, etaboxam, famoxadone, phenoxamyl, phenpi-clonyl, phenpropidine, phenpropimorph, fentinacetate, fentinhydroxide, fluazine, fludioxonil, flumorph, fluoxastrobin, fluchinconazole, flurilazole, flu-tolamil, fluchinconazole, fluzilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxil, furametapir, guazatine, hexaconazole, himexazol, ima-ipron, ima-benz valicarb, isoconazole, isoprotiolan, kasugamycin, crescoxmethyl, manco-zeb, maneb, mefenoxam, mepanapyrim, mepronil, metalaxyl, metco-nasol, metominostrobine / phenominostrobine, metrafenone, miconazole, miclo-butanil, neo-azozine (ferric methanarzonate), nuarimol, orizastrobine, oxadi-xyl, oxpoconazole, penconazole, pencicurone, picobenzamide, picoxistrobam, procenazole, proenazazole, proenazazole, proenazazole, proenazazol oconazole, piraclostrobine, pyrimetanil, pyrifenox, pyrochilon, quinoxifen, siltiofam, simeconazole, sipconazole, spiroxamine, sulfur, tebuconazole, tetra-conazole, thiadinyl, thiabendazole, tyluzamide, thiophanate-methyl, tyram, toli-lfluanide, triadimephon, triadimenol, triarimol, triciclazole, trifloxistrobin, triflumizole, triforin, triticonazole, uniconazole, validamycin, vinclozamide, and nematocides, such as aldicarbon, oxamyl, and phenamyphose; bacterial relapses, such as streptomycin; acarides, such as amitrazine, quinomethionate, chlorobenzylate, chhexatin, dicofol, dienochlorine, ethoxazole, phenazachine, fenbutatin oxide, fenproppatrin, fenproppatrin, phenpiroxymate, hexitiazox, propargite, pyridaben and tebufenpirad; and biological agents, such as Bacillus thuringiensis, including ssp. aizawai and kurstaki, the endotoxin delta Bacillus thuringiensis, baculovirus, and entomopathogenic bacteria, virus and fungi. The compounds of the present invention and their compositions may be applied to genetically transformed plants to express proteins toxic to invertebrate fish (such as Bacillus thuringiensis toxin). The effect of the compounds of the present invention for controlling exogenously applied invertebrate fish may be synergistic with the expressed toxin proteins.

The reference generated to these agricultural protectors is The Pesticide Manual, 12th edition, CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2000.

Preferred insecticides and acaricides for mixing with the compounds of the present invention include pyrethroids, such as acetamipride, cihalotrine, ciflutrin, beta-ciflutrine, sphenvalerate, fenvalerate and thalometrine; carbamates, such as pheno-tricarbon, methomyl, oxamyl and thiodicarbon; neonicotinoids, such as clots-anidine, imidacloprid and thiacloprid; neuronal sodium channel blockers, such as indoxacarb; insecticidal macrocyclic lactones, such as spinozad, aba-mectin, avermectin and emamectin; γ-aminobutyric acid (GABA) antagonists, such as endosulfan, etiprol and fipronil; insecticidal ureas, such as flu-phenoxyiron and triflumuron; juvenile hormone imitators, such as diophenolane and pyriproxifene, pimetrozine and amitraza. Preferred biological agents for mixing with the compounds of the present invention include Bacillus thuringiensis and endotoxin delta Bacillus thuringiensis, as well as naturally occurring and genetically modified viral insecticides, including members of the Baculovirid family, as well as entomophagous fungi.

Most preferred mixtures include a mixture of a compound of the present invention with cihalotrine, a mixture of a compound of the present invention with beta-ciflutrine; a mixture of a compound of the present invention with sphenvalerate; a mixture of a compound of the present invention with methyl; a mixture of a compound of the present invention with imidacloprid; a mixture of a compound of the present invention with thiacloprid; a mixture of a compound of the present invention with indoxacarb; a mixture of a compound of the present invention with abamectin; a mixture of a compound of the present invention with endosulfan; a mixture of a compound of the present invention with etiprol; a mixture of a compound of the present invention with fipronil; a mixture of a compound of the present invention with flufenoxuron; a mixture of a compound of the present invention with pyriproxifene; a mixture of a compound of the present invention with primetrozine; a mixture of a compound of the present invention with amitrazone; a mixture of a compound of the present invention with Bacillus thuringiensis uizawai or Bacillus thuringiensis hurstaki, and a mixture of a compound of the present invention with Bacillus thuringiensis delta endotoxin.

In some cases, combinations with other agents or compounds for fighting invertebrate fish having a similar spectrum of control, but a different mode of action, will be particularly advantageous for enhancing resistance. Thus, the compositions of the present invention may contain additionally о biologically effective amount of at least one additional agent or compound for the control of invertebrate fish, having a similar spectrum of control, but a different mode of action. Contact of a genetically modified plant to express a plant protection compound (eg, protein) or plant site with о effective biological amount of a compound of the invention may also provide a broad spectrum of plant protection and may be advantageous for intensification of resistance.

Invertebrate fish are combated in agronomic and non-agronomic applications by applying one or more compounds of the present invention, in an efficient amount, in the environment of fish, including in the place of agronomic and / or non-agronomic infection, on the land to be protected. , or directly on the fish to be fought. Thus, the present invention further includes a method of controlling invertebrates in agronomic and / or non-agronomic applications, which includes contact of invertebrates or their environment with an effective biological quantity of one or more compounds of the invention; or with a composition containing at least one such compound or a composition containing at least one such compound and an effective amount of at least one biologically active agent or compound

MD 3864 Fl 2009.03.31 additional. Examples of suitable compositions containing a compound of the invention and an effective amount of at least one additional biologically active agent or compound include granular compositions wherein the additional biologically active compound is present in the same granule as the compound of the invention or in separate granules thereof. of the compound of the present invention.

The preferred contact method is spraying. Alternatively, a granular composition which confines a compound of the invention may be applied to the leaves of the plant or to the soil. The compounds of the present invention are effectively used by plant absorption, by contact with the plant with о composition which confines a compound of the present invention applied by impregnating the soil with о liquid solution, о granular solution in the soil, by treating the nursery or through a transplant ball. The compounds are also effective by topically applying a composition that confines a compound of the present invention instead of the infestation. Other contact methods include introducing a compound or composition according to the invention through direct or subsequent spray solutions, aerial spraying solutions, gels, seed fattening, microcapsulation, systematic absorption, baits, label fixing, pills (food cocoons) , aerosol sprayers, fumigants, aerosols, powders and more. The compounds of the present invention may also be impregnated in materials for making devices for fighting invertebrates (eg, insect nets).

A compound of the present invention may be incorporated into a bait composition that is consumed by о invertebrate fish or used in devices such as traps, bait stations and the like. This bait composition may be in the form of granules containing (a) an active ingredient, namely a compound of formula 1, an N-oxide, or its salt, (b) one or more nutrients, (c) optionally an attractant, and (d) optional to one or more moisturizers. It should be noted that the pellets or compositions of bait containing about 0.001 ... 5% of active ingredient, about 40 ... 99% of nutrient and / or attractant, and optionally about 0.05 ... 10% of moisturizers they are effective in fighting invertebrate soil fish in very low application ratios, particularly in doses of active ingredient that are lethal rather by injection than by direct contact. It should be noted that some nutrients will work both as a source of food and as an attractant. Nutrients include carbohydrates, proteins and lipids. Examples of nutrients are vegetable flour, sugar, starch, animated fat, vegetable oil, yeast extracts and dry milk. Examples of attractants are odorant and flavoring agents, such as plant or fruit extracts, perfume, or other plant or animal component, pheromones or other known agents that attract invertebrate fish. Examples of humidifiers, which are moisture retention agents, are glycols and other polyols, glycerine and sorbitol. Important is о bait composition (and о method of using this bait composition) used to combat invertebrate fish that include individually or in combination ants, termites and cockroaches. A device for combating invertebrate fish may contain the present bait composition and a slot provided for the location of the bait composition, the housing having at least one orifice executed so as to allow the invertebrate fish to enter through it and gain access to the bait composition in one. place outside the place, and where the place is additionally provided to be located in or near the place of possible or known activity of invertebrate fish.

The compounds of the present invention can be applied in a pure state, but most commonly applicable о solution that includes one or more compounds with convenient carriers, diluents and surfactants and possibly in combination with a foodstuff depending on the intended use О method of application Preferably it includes spraying an aqueous dispersion or a refined oil solution of the compounds. Combinations with spray oils, concentrations of powder-verifiable oils, adhesives, adjuvants, other solvents, and synergists, such as piperonyl butoxide, often increase the effectiveness of the compounds. For non-economical uses, these spray solutions can be applied from spray containers, such as a tin box, a bottle or another container either through a pump or by releasing them from an airtight container, e.g. о tin box with hermetic spray solution. Thus, these spray compositions may have various forms, for example, solutions, aerosols, sparks, fumes or mist. These spray compositions may additionally include explosives, foams, etc. as the case. Important is a spray composition which confines a compound or composition of the present invention and an explosive substance. Representative explosive substances include, but are not limited to, methane, ethane, propane, isopropane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluoroacarbones, methyl ether and mixtures thereof. Importance is a spray composition (and method of using this spray composition from a spray container) used to combat invertebrate fish that include, individually or in combination, mosquitoes, molluscs, black lice, detonated mussels, reed moths, reed mites - horses, wasps, buzzards, ticks, spiders, ants, etc.

The application rule required for effective control (eg, effective biological quantity) will depend on the factors for controlling invertebrate species, such as the life cycle of fish, their stage of life, their size, location, time of year, host animal or host plant, cravings, mating behavior, environmental humidity, temperature, etc. Under normal circumstances, the introduction rules of about 0.01 ... 2 kg of active ingredient per hectare are sufficient for combating fish in agronomic systems, but at least 0.0001 kg / hectare can be sufficient or at most 8 kg / hectare may be required. For non-agronomic applications, the effective use standards will range from about 1.0 to 50 mg / m², but at least

MD 3864 In 2009.03.31

0.1 mg / m² may be sufficient or at most 150 mg / m² may be necessary. A person skilled in the art can easily determine the effective biological quantity required for the desired level of control of invertebrate fish.

The following tests demonstrate the efficacy of combating the compounds of the present invention in specific fish. Fighting efficiency is the inhibition of the development of invertebrate fish (including mortality) which causes considerably reduced feeding. However, the fish control offered by the compounds is not limited to these species. See index table A, В and C for descriptions of the compounds. The following abbreviations are used in the following table of indices: i represents iso, t - tertiary, Me - methyl, Et - ethyl, Pr - propyl, z - Pr - isopropyl, c - Pr - cyclopropyl, Bu - butyl and CN - cyan. Abbreviation Ex. represents Example and is followed by a number indicating the example in which the compound is prepared.

TABLE OF CONTENTS A

R?

N

<img file="MD3864B2_D0034.tif" />

<td>Compound</td><td>ii</td><td>В *</td><td> £3</td><td>Ki</td><td></td><td></td>

<td>l (Ex.l)</td><td>Me</td><td>CF3</td><td>of</td><td>H</td><td>h</td><td> 200...202</td>

<td>2 (Ex.2)</td><td>Me</td><td>CF3</td><td>of</td><td>Me</td><td>H</td><td> 214...216</td>

<td>3 (Ex.3)</td><td>Me</td><td>of</td><td>of</td><td>Me</td><td>H</td><td> *</td>

<td>4 {eg 4)</td><td>Me</td><td>of</td><td>but</td><td>H</td><td>H</td><td> &gt;255</td>

<td>5 (Ex.5)</td><td>Me</td><td>br</td><td>of</td><td>Me</td><td>H</td><td> «</td>

<td>6 (Exl 6)</td><td>Me</td><td>Вт</td><td>of</td><td>H</td><td>H</td><td> &gt;255</td>

<td>7 (Ex 7)</td><td>of</td><td>of</td><td>of</td><td>Me</td><td>H</td><td> 197.200</td>

<td> 8</td><td>Me</td><td>CF₃</td><td>of</td><td>i-Pr</td><td>H</td><td> &gt;250</td>

<td> 9</td><td>of</td><td>Cl</td><td>of</td><td>i-Pr</td><td>H</td><td> 213...215</td>

<td> 10</td><td>of</td><td>br</td><td>of</td><td>i-Pr</td><td>H</td><td> 222...225</td>

<td> 11</td><td>of</td><td>br</td><td>of</td><td>i-Pr</td><td>Me</td><td> 224-.226</td>

<td> 12</td><td>of</td><td>br</td><td>of</td><td>Me</td><td>H</td><td> 198...201</td>

<td> 13</td><td>of</td><td>of</td><td>of</td><td>i-Pr</td><td>Me</td><td> 238.241</td>

<td> 14</td><td>of</td><td>br</td><td>of</td><td>H</td><td>H</td><td> &gt;255</td>

<td> 15</td><td>of</td><td>F</td><td>of</td><td>i-Pr</td><td>H</td><td> 162...166</td>

<td> 16</td><td>Cl</td><td>F</td><td>of</td><td>Me</td><td>H</td><td> 205...208</td>

<td> 17</td><td>of</td><td>br</td><td>F</td><td>i-Pr</td><td>H</td><td> 230...232</td>

<td> 18</td><td>of</td><td>br</td><td>F</td><td>Me</td><td>H</td><td> *</td>

<td> 19</td><td>of</td><td>br</td><td>F</td><td>H</td><td>H</td><td> &gt;255</td>

<td> 20</td><td>Me</td><td>CF3</td><td>of</td><td>Me</td><td>Me</td><td> 227...230</td>

MD 3864 In 2009.03.31

<td>Compound</td><td> -</td><td> £2</td><td>Й</td><td></td><td></td><td>LL Inquiry</td>

<td> 21</td><td>of</td><td>CF₃</td><td>of</td><td>i-Pr</td><td>h</td><td> 247.249</td>

<td> 22</td><td>of</td><td>CF3</td><td>of</td><td>Me</td><td>H</td><td> 215.217</td>

<td> 23</td><td>of</td><td>CF3</td><td>of</td><td>H</td><td>H</td><td> &gt;255</td>

<td> 24</td><td>Me</td><td>of</td><td>of</td><td></td><td>H</td><td> *</td>

<td> 25</td><td>Mo</td><td>br</td><td>of</td><td>I Pi</td><td>H</td><td> «</td>

<td> 26</td><td>Me</td><td>of</td><td>of</td><td>CH₂CN</td><td>H</td><td> 213...215</td>

<td> 27</td><td>Me</td><td>br</td><td>of</td><td>ch₂cn</td><td>H</td><td> 225...227</td>

<td> 28</td><td>Me</td><td>och₂cf.₃</td><td>of</td><td>Me</td><td>Me</td><td> 132...135</td>

<td> 29</td><td>Me</td><td>OCH2CF3</td><td>of</td><td>Me</td><td>H</td><td> 162...165</td>

<td> 30</td><td>Me</td><td>CF₃</td><td>of</td><td>t-Bu</td><td>H</td><td> &gt;250</td>

<td> 31</td><td>Me</td><td>CF3</td><td>of</td><td>ch₂cn</td><td>H</td><td> 250...251</td>

<td> 32</td><td>Me</td><td>CF₃</td><td>of</td><td>et</td><td>H</td><td> 150...151</td>

<td> 33</td><td>Me</td><td>of</td><td>of</td><td>et</td><td>H</td><td> *</td>

<td> 34</td><td>Me</td><td>of</td><td>of</td><td>t-Bu</td><td>H</td><td> &gt;255</td>

<td> 35</td><td>Me</td><td>br</td><td>of</td><td>et</td><td>H</td><td> *</td>

<td> 36</td><td>Me</td><td>br</td><td>ά</td><td>t-Bu</td><td>H</td><td> &gt;255</td>

<td> 37</td><td>Me</td><td>CF3</td><td>of</td><td>СН (СНз) СН₂8Ме</td><td>H</td><td> 208-209</td>

<td> 39</td><td>Me</td><td>br</td><td>of</td><td>Me</td><td>Me</td><td> 262...264</td>

<td> 40</td><td>Me</td><td>ОСН₂СРз</td><td>of</td><td>i-Pr</td><td>H</td><td> 164...167</td>

<td> 41</td><td>Me</td><td>ОСН₂СРз</td><td>of</td><td>t-Bu</td><td>H</td><td> *</td>

<td> 42</td><td>Me</td><td>OCH2CF3</td><td>of</td><td>Me</td><td>Me</td><td> 212...214</td>

<td> 43</td><td>Me</td><td>OCH2CF3</td><td>of</td><td>et</td><td>H</td><td> 168...171</td>

<td> 44</td><td>Me</td><td>OCH2CF3</td><td>of</td><td>ch₂cn</td><td>H</td><td> 207...211</td>

<td> 45</td><td>Me</td><td>of</td><td>of</td><td>Me</td><td>Me</td><td> 261...263</td>

<td> 46</td><td>Me</td><td>CF3</td><td>F</td><td>Me</td><td>H</td><td> 211...212</td>

<td> 47</td><td>Me</td><td>CF3</td><td>F</td><td>H</td><td>H</td><td> 138...139</td>

<td> 48</td><td>Me</td><td>CF3</td><td>F</td><td>et</td><td>H</td><td> 219...220</td>

<td> 49</td><td>Me</td><td>br</td><td>F</td><td>Me</td><td>H</td><td> 152..153</td>

<td> 50</td><td>Me</td><td>br</td><td>F</td><td>H</td><td>H</td><td> 162...164</td>

<td> 51</td><td>Me</td><td>br</td><td>F</td><td>et</td><td>H</td><td> 201...202</td>

<td> 52</td><td>Me</td><td>CF3</td><td>F</td><td>i-Pr</td><td>H</td><td> 229...230</td>

<td> 53</td><td>Me</td><td>br</td><td>F</td><td>i-Pr</td><td>H</td><td> 159...160</td>

<td> 54</td><td>Me</td><td>CF₃</td><td>F</td><td>СН (СНз) СН₂ЗМе</td><td>H</td><td> 209...210</td>

<td> 55</td><td>F</td><td>br</td><td>of</td><td>Me</td><td>Ή</td><td> 209...210</td>

<td> 63</td><td>Me</td><td>br</td><td>of</td><td>СН (СНз) СН₂2Ме</td><td>H</td><td> 180...181</td>

<td> 64</td><td>Me</td><td>of</td><td>of</td><td>СН (СНз) СН₂ЗМе</td><td>H</td><td> 193...194</td>

<td> 65</td><td>Me</td><td>br</td><td>of</td><td>C (CH₃)₂CH₂SMe</td><td>H</td><td> 161...162</td>

MD 3864 In 2009.03.31

<td>Compound</td><td></td><td></td><td> 22</td><td>κί</td><td></td><td>-'- Ρ · ΡΟ</td>

<td> 66</td><td>Me</td><td>CF₃</td><td>of</td><td>C (CH₃)₂CH2SMe</td><td>h</td><td> 250.250</td>

<td> 67</td><td>Me</td><td>of</td><td>of</td><td>C (CH₃)₂CH2SMc</td><td>H</td><td> 234...235</td>

<td> 68</td><td>Me</td><td>cfj</td><td>of</td><td>t-Pr</td><td>H</td><td> 159.160</td>

<td> &amp;</td><td>Me</td><td>CF₃</td><td>of</td><td>(СН ^ зОМе</td><td>H</td><td> 206...207</td>

<td> 70</td><td>Me</td><td>of</td><td>of</td><td>c-Pr</td><td>а</td><td> 156—157</td>

<td> 71</td><td>Me</td><td>of</td><td>of</td><td>(CH OMe</td><td>и</td><td> 118...119</td>

<td> 72</td><td>Me</td><td>br</td><td>of</td><td>(CH OMe</td><td>Η</td><td> 216...217</td>

<td> 73</td><td>Me</td><td>br</td><td>of</td><td>OPR</td><td>Η</td><td> 159.160</td>

<td> 74</td><td>Me</td><td>CF₃</td><td>of</td><td>Me</td><td>Η</td><td> 235.236</td>

<td> 75</td><td>Me</td><td>of? 3</td><td>of</td><td>СН2СН (СНз) 2</td><td>Η</td><td> 257.258</td>

<td> 76</td><td>Me</td><td>br</td><td>of</td><td>СН₂(С-Рг)</td><td>Η</td><td> 223...224</td>

<td> 77</td><td>Me</td><td>br</td><td>of</td><td>СН₂СН (СНз) 2</td><td>Η</td><td> 245...246</td>

<td> 78</td><td>Me</td><td>br</td><td>of</td><td>СН (СНз) СН28 (О) Ме</td><td>Η</td><td> 157.158</td>

<td> 79</td><td>Me</td><td>br</td><td>Cl</td><td>СН (СНз) СН28 (О) 2Ме</td><td>Η</td><td> 169-170</td>

<td> 80</td><td>Me</td><td>of</td><td>of</td><td>СН (С31зХСН2) 28Ме</td><td>Η</td><td> 190-191</td>

<td> 81</td><td>Me</td><td>br</td><td>of</td><td>aH (CH₃XCH2)₂SMe</td><td>Η</td><td> 188...190</td>

<td> 82</td><td>Me</td><td>CF₃</td><td>Cl</td><td>CH (CH₃XCH2) 2SMc</td><td>Η</td><td> 134...135</td>

<td> 83</td><td>Me</td><td>of</td><td>of</td><td>CH (CH₃) (CH 2) 2 S (O) 2 Me</td><td>Η</td><td> 186...187</td>

<td> 84</td><td>Me</td><td>br</td><td>Cl</td><td>CH (CH₃) (CH 2) 2 S (O)₂Me</td><td>Η</td><td> 182...183</td>

<td> 85</td><td>br</td><td>br</td><td>of</td><td>Me</td><td>Η</td><td> 214-215</td>

<td> 86</td><td>br</td><td>br</td><td>of</td><td>i-Pr</td><td>Η</td><td> 166-167</td>

<td> 87</td><td>br</td><td>br</td><td>of</td><td>CH₂CN</td><td>Η</td><td> 226...227</td>

<td> 88</td><td>Me</td><td>of</td><td>F</td><td>Me</td><td>Η</td><td> 149...150</td>

<td> 89</td><td>Me</td><td>of</td><td>F</td><td>H</td><td>Η</td><td> 146...147</td>

<td> 90</td><td>Me</td><td>of</td><td>br</td><td>H</td><td>Ή</td><td> 189.190</td>

<td> 91</td><td>Me</td><td>of</td><td>br</td><td>Me</td><td>Η</td><td> 149-150</td>

<td> 92</td><td>Me</td><td>of</td><td>br</td><td>i-Pr</td><td>Η</td><td> 119.120</td>

<td> 93</td><td>Me</td><td>of</td><td>br</td><td>Me</td><td>Me</td><td> 247.248</td>

<td> 94</td><td>Me</td><td>br</td><td>br</td><td>H</td><td>Η</td><td> 255 .256</td>

<td> 95</td><td>Me</td><td>br</td><td>br</td><td>Me</td><td>Η</td><td> 183.184</td>

<td> 96</td><td>Me</td><td>br</td><td>br</td><td>i-Pr</td><td>Η</td><td> 235...236</td>

<td> 97</td><td>Me</td><td>br</td><td>br</td><td>Me</td><td>Me</td><td> 242...243</td>

See index table C for MRI data

MD 3864 In 2009.03.31

INDEX TABLE В

<img file="MD3864B2_D0035.tif" />

Λ

RS

<td>Compound</td><td> £1</td><td>В2</td><td></td><td>Bi</td><td>Βί</td><td></td><td>ώ</td><td>Jim</td>

<td> 98</td><td>Me</td><td>br</td><td>Cl</td><td>Me.</td><td>H</td><td>H</td><td>of</td><td> 145-146</td>

<td> 99</td><td>Me</td><td>br</td><td>of</td><td>et</td><td>H</td><td>H</td><td>of</td><td> 148.149</td>

<td> 100</td><td>Me</td><td>br</td><td>of</td><td>i-Pr</td><td>H</td><td>H</td><td>of</td><td> 174...175</td>

<td> 101</td><td>Me</td><td>of</td><td>Cl</td><td>bt</td><td>H</td><td>H</td><td>of</td><td> 167...168</td>

<td> 102</td><td>Me</td><td>of</td><td>of</td><td>i-Pr</td><td>H</td><td>H</td><td>of</td><td> 189...190</td>

<td> 103</td><td>Me</td><td>of</td><td>Cl</td><td>Me</td><td>H</td><td>H</td><td>Cl</td><td> 185.186</td>

<td> 104</td><td>Me</td><td>br</td><td>of</td><td>Me</td><td>H</td><td>F</td><td>H</td><td> 152...153</td>

<td> 105</td><td>Me</td><td>br</td><td>Cl</td><td>i-Pr</td><td>H</td><td>F</td><td>H</td><td> 134...136</td>

<td> 106</td><td>Me</td><td>of</td><td>F</td><td>H</td><td>H</td><td>H</td><td>F</td><td> 212.213</td>

<td> 107</td><td>Me</td><td>of</td><td>F</td><td>Me</td><td>H</td><td>H</td><td>F</td><td> 214...215</td>

<td> 108</td><td>Me</td><td>br</td><td>F</td><td>H</td><td>H</td><td>H</td><td>F</td><td> 204...205</td>

<td> 109</td><td>Me</td><td>br</td><td>F</td><td>Me</td><td>H</td><td>H</td><td>F</td><td> 222...223</td>

<td> 110</td><td>Me</td><td>br</td><td>F</td><td>bt</td><td>H</td><td>H</td><td>F</td><td> 200.201</td>

<td> 111</td><td>Me</td><td>br</td><td>F</td><td>i-Pr</td><td>H</td><td>H</td><td>P</td><td> 203...204</td>

<td> 112</td><td>Me</td><td>Cl</td><td>F TABLE</td><td colspan="2">Et H INDEX C</td><td>H</td><td>F</td><td> 195...196</td>

Nr. Compound Data^]H NMR (in CDC1 solution₃, unless otherwise indicated) (CDCI3) 10.55 (s, 1H), 8.45 (d, IB), 7.85 (dd, IB), 7.55 (s, 2H), 7.40 ( dd, 1H), 6.97 (s, IB), 6.30 (bq, .lB), 2.98 (d, 3B), 2.24 (s, 3H) (CDCI3) 10.55 (a, IB), 8.45 (d, 1H), 7.85 (dd, IB), 7.57 (m, 2H), 7.37 (dd, IB), 7.05 (s, 1H), 6, 30 (bq, IB) 2.98 (d, 3H), 2.24 (s, 3H) (CDCI3) 10.10 (br s, 1H), 8.38 (d, IB), 7.75 (s , IB), 7.65 (s, IB), 7.60 (ш, IB), 7.34 (и, IB), 7.10 (s, Щ), 6.58 (bq, IB) 2, 96 (s, 3B) (CDCl3) 10.12 (s, 1H), 8.56 (d, IB), 7.85 (d, IB), 7.58 (m, 2H), 7.40 (dd, IB), 6.97 (в, 1H), 6.00 (bd, IB) 4.22 (m, IB), 2.25 (s, 3H) , 126 (d, 6B) (CDCI3) 10.60 (s, IB), 8.47 (d, IB), 7.85 (dd, IB), 7.56 (s, 2B), 7.39 ( dd, IB), 7.06 (s, IB), 6.04 (bd, IB) 4.20 (m, IB), 2.24 (s, 3B), 1.26 (s, 6H)

Nr. Compound Data 'MRI (CDCI3 solution, unless otherwise indicated)

MD 3864 At 2009.03.31 (CDdj) 10.60 (s, IB), 8.45 (d, IB), 7.85 (d, IB), 7.58 (s, 2H), 7.39 (m , 1H), 6.97 (s, IB), 6.20 (bt, IB) 3.46 (m, 2H), 2 J5 (s, 3H), 1.25 (t, 3B) ₃₅ (CDCI3) 10.60 (s, IB), 8.46 (d, IB), 7.85 (d, IB), 7.57 (s, 2H), 7.38 (m, IB), 7, 05 (s, IB), 6.25 (bt, 1H) 3.46 (m, 2H), 2.24 (s, 3H), 1.25 (ζ 3H) ₄₁ (CDCI3) 10.40 (s, IB), 8.47 (d, IB), 7.85 (d, IB), 7.50 (s, 2H), 7.37 (dd, IB), 6, 63 (s, IB), 5.97 (s, IB) 4.68 (q, 2H), 1.42 (e, 9B)

BIOLOGICAL EXAMPLES OF THE INVENTION

TEST A '

For the evaluation of the control of the cabbage moth (Plutella xylostella) the test model consisted of an open container with о radish plant of 12 ... 14 days inside. It was preliminary infested with 10 ... 15 newborn larvae on an insect fragment by using a probe for sampling within the fixed insect fragment, in which the larvae develop and the transfer of the sample with larvae into the test device.

Test compounds were made using a solution containing 10% acetone, 90% water and 300 ppm non-ionic surfactant X-77® Lo-Foam Spreader Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries Inc., Greeley, Colorado, USA). Obfinufi compounds were introduced into 1 mL of liquid through a customized 1/8 JJ body spray capsule (Spraying Systems Co., Wheaton, Illinois, USA) positioned 127 cm (0.5 inches). above the top of each test model. All experimental compounds in these tests were sprayed at 50 ppm and replicated 3 times. After spraying the obtained test compound, each test device was left to dry for 1 hour and afterwards a black protective cap was placed on the top. The test models were finished 6 days in a room of growth at 25 ° C and the relative humidity of 70%. The damage caused to the plant by feeding was visually evaluated on the basis of the leaves consumed.

From the following test compounds have provided levels of protection of the plants from very good to excellent (a damage by feeding of 20% or more): 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, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 88, 89, 90, 91, 92, 94,

95, 96, 97, 98, 99, 100, 101,102, 103, 106, 108, 109, 110, 111 and 112.

TEST В

For the evaluation of moth butterfly control (Spodoptera frugiperda) the test model consisted of a small open container with о maize plant 4-5 days inside. It was pre-infested (using о core sample) with 10 ... 15 larvae at 1 day old per о piece of insect retention.

Test compounds were made and sprayed at 50 ppm as described for Test A. The applications were replicated 3 times. After spraying, the test models were stained in a growth chamber and then visually evaluated as described for Test A.

From the test compounds, the following provided excellent levels of plant protection (20% or more feeding damage): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 21, 22, 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, 63, 64, 65, 66, 67, 68, 70, 73, 74, 76, 78, 88, 91, 92, 94, 95, 96, 98, 99,100, 101, 102, 103, 106, 109, 110, 111 and 112.

TEST C

In order to evaluate the control of the green-peach louse (Myzys persioae) by systemic and / or contact means, the test model consisted of a small open container with an о radish plant of 12 ... 15 days inside. This was infested by placing on the leaf the test plant of 30 ... 40 aphids on the о piece of leaf cut from the crop plant (the method of cutting the leaf). The larvae moved to the test plant immediately after cutting the leaf peel. After preliminary infestation, the soil in the test model was covered with a layer of sand.

Test compounds were made using о solution containing 10% acetone, 90% water and 300 ppm non-ionic surfactant X-77® Lo-Foam Spreader Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries , Inc.). The formed compounds were introduced into 1 mL of liquid through an SUI2 spray capsule with a 1/8 JJ custom-made body (Spraying Systems Co.) positioned 127 cm (0.5 inches) above the top edge of each device. Testing. After spraying the formed test compound, each test model was left to dry for 6 days in a growth chamber at 19 ... 21 ° C and relative humidity of 50 ... 70%. Each test model was then visually evaluated for insect mortality.

From the test compounds, the following resulted in mortality of at least 80%: 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, 38.40, 41, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56, 63, 65, 66, 67, 68, 69, 70, 73, 74, 76, 78, 88, 89, 90, 91, 92, 94, 95, 96, 98, 99, 100, 101, 102, 103, 106, 108, 109, 110, 111 and 112.

MD 3864 In 2009.03.31

TEST D

For the evaluation of the control of the potato chicory (Empoasca fabae Homs) by systemic and / or contact means, the test model consisted of a small open container with о Longio bean plant (initial sunflower leaves) inside. Above the ground was added white sand and one of the initial leaves was cut until introduced. The test compounds were made and sprayed at 250 ppm and replicated 3 times, as described for Test C. After spraying, the test models were left to dry for 1 hour, before being infested with 5 cicadas (adult insects from 18 to 21 days). A black protective cap was placed above the cylinder. The test models were maintained for 6 days in a growth chamber at room temperature

19 .. .21 ° C and relative humidity of 50 ... 70%. Each test model was then visually evaluated for insect mortality.

From the test compounds, the following resulted in mortality of at least 80%: 1, 3, 4, 5, 6, 8, 10, 12, 16.17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 33, 34, 35, 37, 38, 40.41, 43.44, 46.47, 48.49, 50, 51, 52, 53, 54, 55, 56, 63.66, 67, 68, 70, 73, 76, 88, 89, 90, 94.95, 98, 99.101, 103, 106, 108, 109, 110, 111 and 112.

TEST E

For the control of evaluation of cotton-and-cucumber lice (Aphis gossypii) by systemic and / or contact means, the test model consisted of a small open container with о cotton plant of 6 .. .7 days inside . It was preliminary infested with 30 ... 40 insects per о leaf piece according to the leaf cutting method described for Test C, and the soil in the test model was covered with a layer of sand.

The test compounds formulated and sprayed at 250 ppm, as described for Test D. The applications were replicated 3 times. After spraying, the test models were stained in a growth chamber and then visually evaluated, as described for Test D.

Of the tested compounds, the following resulted in mortality of at least 80%: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 , 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 32, 33, 34, 35, 36, 37, 38, 39, 40,41,42,43, 44, 46 , 47, 48, 49, 50, 51, 52, 53, 55, 56, 63, 69, 71, 72, 74, 76, 78, 79, 81, 84, 88, 89, 90, 91, 92, 95 , 96, 97, 98, 99, 100, 101, 102, 103, 106, 108, 109, 110, 111 and 112.

TEST F

For the evaluation control (Peregrinus maidis) by systemic and / or contact means, the test model consisted of a small open container with о maize plant (spike) 3 to 4 days inside. White sand was added to the soil surface until applied. The test compounds were made and sprayed at 250 ppm and replicated 3 times, as described for Test C. After spraying, the test models were left to dry within 1 hour until their preliminary infestation with 10 ... 20 insects (nymphs at the age of 18 ... 20 days) sprinkling them on the sand with the help of a spray. salt sprinkler device. A black protective cap was placed above the cylinder. The test models were maintained for 6 days in the growth chamber at 19 ... 21 ° C and the relative humidity of 50 ... 70%. Each test model was then visually evaluated for insect mortality. From the tested compounds, the following resulted in at least 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 18, 20, 24, 25, ' 26, 27, 28, 29, 32, 33, 35, 37, 38, 39, 40, 41, 43, 45, 46, 47, 48, 49, 50, 51, 53, 56, 88, 89, 90, 91, 94, 95, 108 and 109.

TEST G

For the evaluation control Bermisia tabacia, the test model was made of a cotton plant.

14 .. .21 days grown on Redi-earth® media (Scotts Co.) with at least two true leaves infested with stage 2 and 3 nymphs on the dorsal side of the leaves.

The test compounds were made up of no more than 2 mL of acetone and then diluted with water to 25 ... 30 mL. Compounds were introduced using о flat spray jet capsule (Spraying Systems 122440) at 10 psi (69 kPa). The plants were sprayed to the surface with a rotary sprayer. All experimental compounds in this sieve were sprayed at 250 ppm and replicated 3 times. After spraying the test compound, the test models were maintained for 6 days in a growth chamber at 28 ° C by day and 24 ° C by night and relative humidity of 50 ... 60%. Then the leaves were removed and the living and dead nymphs were counted to calculate the mortality rate.

Of the compounds tested, the following resulted in mortality of at least 80%: 2, 3, 4, 5, 7, 8, 9, 10, 24, 25, 26, 27, 28, 30, 32, 33, 34 , 35, 38, 41, 46, 48, 49, 51, 52, 53, 66, 67, 70, 73, 88 '92 and 98.

TEST H

For the evaluation of the displacement of the compounds in plants and the control of the green-peach louse (Myzus persicae) and the potato cicada (Empoasca fabae) after the foliar movement of the compound through the plant, the test model consisted of a small open container with о radish plant 12 ... 15 days (for testing the lice-green-peach) or о Longio bean plant for 5 ... 6 days (for testing the potato chicory).

Test compounds were made using о solution containing 10% acetone, 90% water and 600 ppm surfactant X-77® Lo-Foam Spreader Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.). Compounds were applied in 20 ill. by pipetting to 2 larger photosynthetic active leaves. Tofi experimental compounds from this sieve were applied at 1000 ppm, and the tests were replicated 3 times. After introducing the test compounds, the variety in this test model a

MD 3864 Fl 2009.03.31 was covered with a layer of sand and each test model was left to dry for 1 hour, after which a black protective cap was placed over it. The test models were maintained in a growth chamber at a temperature of about 20 ° C and a relative humidity of 50 ... 70%.

Over 2 days, the treated leaves were coated on all sides with a fine plastic screen, but with the leaf stem intact and attached to the plant to allow normal vascular movement and photosynthesis. The plants were then infested with 20 ... 30 aphids (radish) or 20 chickpeas (beans) and kept in a growth chamber for 8 days. Each test device was then visually evaluated for estimating insect mortality, which contacted and fed the untreated plant tissues.

The results of mortality of lice-green-peach (% M PVP) and mortality of potato chicory (% Μ CC) are inserted in table A.

TABLE A

Percentage of insect mortality

<td>Compound</td><td>% MCC</td><td>% M PVP</td>

<td> 1</td><td> 58</td><td> 87</td>

<td> 3</td><td> 96</td><td> 81</td>

<td> 4</td><td> 93</td><td> 78</td>

<td> 5</td><td> 96</td><td> 94</td>

<td> 6</td><td> 77</td><td> 100</td>

<td> 26</td><td> 73</td><td> 67</td>

<td> 27</td><td> 13</td><td> 57</td>

TESTULI

For the evaluation of the displacement of the compounds in plants and of the control of the lice-green-of-peach (My / us persicae) and of the cicada-potato (Empoasca fabae) after the xylene movement of the compound from the introduction into the soil to the leaves through the roots, the test model it consisted of a small open container with о radish plant of 12 ... 15 days (for testing the lice-green-of-peach) or о bean plant of Longio of 5 ... 6 days (for testing of the chicory- potato).

The test compounds were made using о solution containing 10% acetone, 90% water and 600 ppm non-ionic surfactant X-77® Spreader LO-Foam Formula containing alkylaryl polyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries , Inc.). The constituent compounds were applied in 20 ml of solution through a pipette into the soil at the base of the plant. All experimental compounds! from this sieve were applied at 1000 ppm, and the tests were replicated 3 times. After the introduction of the test compounds, each test model was left to dry for 1 hour. The variety of each model was covered with a layer of sand and then a black protective cap was placed above. The test models were kept in a growth chamber at a temperature of about 20 ° C and a relative humidity of 50 ... 70%.

Over 2 days, the plants were infested with 20 ... 30 aphids (radish) or 20 cicorife (beans) and kept in a growth chamber for 5 days. Each test model was then visually evaluated for insect mortality, which contacted and fed on untreated plant tissues.

The results regarding the mortality of the green-peach louse (% M PVP) and the mortality of the cicorife-potato (% M CC) are inserted in table B.

TABLE В

Percentage of insect mortality

Compound% MCC

100 % M PVP

56

95

100