Ortho-substituted arylamides, method for pest controlling, composition for pest controlling, and intermediate

FIELD: organic chemistry, agriculture.

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

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

15 cl, 21 tbl, 9 ex

 

Background of the invention

The present invention relates to certain ortho-substituted arylamides, their N-oxides, salts and compositions, suitable for agricultural or non-agricultural applications, including the compounds listed below, and to methods of their use for combating invertebrate pests in agriculture and in the non-agricultural sector.

The control of invertebrate pests is extremely important to achieve high crop yields. The damage caused by insect pests of cultivated and stored crops, leads to a significant reduction in productivity and, thus, to higher prices for consumers. The control of invertebrate pests in sectors such as forestry, cultivation of greenhouse crops, ornamental plants, plants, planted to protect other crops, stored food products, and products derived from fibrous crops, livestock rearing, housekeeping, and health care and veterinary medicine, is also important. Many products are commercially available for these purposes, but there remains a need for new compounds which are more effective, cheaper, less toxic, more environmentally friendly and with a different action type.

NL 9202078 discloses derivatives of N-acylanthranilic acid of the Formula I as insecticide.

where, inter alia, X represents a simple bond; Y represents H or C1-C6alkyl; Z represents NH2, NH(C1-C3alkyl) or N(C1-C3alkyl)2; and R1for R9independently represent H, halogen, C1-C6alkyl, phenyl, hydroxy, C1-C6alkoxy or1-C7acyloxy.

Brief description of the invention

The present invention relates to compounds of Formula I and their N-oxides and salts

where

J is a phenyl ring, a 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed carbobicyclic or heterobicyclic ring system, each ring or ring system substituted by one to four substituents independently selected from R5;

K represents a-NRlC(=A)-, -N=C(GR6)- or-NR1SO2-;

L represents-C(=B)NR2-, -C(GR6)=N-, -SO2NR2-,

-C(=B)O - or-C(=B);

A and B independently represent O, S, NR8, NOR8, NN(R8)2, S=O, N-CN or N-NO2;

each G independently represents O, S or NR8;

R1 represents H; or (C1-C6alkyl, C2-C6alkenyl,2-C6quinil or3-C6cycloalkyl, each optionally substituted by one or more substituents independently selected from the group including halogen, CN, NO2, hydroxy, C1-C4alkoxy,

With1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C2-C4alkoxycarbonyl,1-C4alkylamino,2-C8dialkylamino and C3-C6cyclooctylamino; or

R1represents a C2-C6alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl or3-C8dialkylaminoalkyl;

R2represents H, C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,1-C4alkoxy, C1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,2-C6alkoxycarbonyl or

With2-C6alkylsulphonyl;

R3represents H; C1-C4alkoxy; C1-C4alkylamino;

With2-C8dialkylamino; C3-C6cyclooctylamino; C2-C6alkoxycarbonyl or2-C6/sub> alkylsulphonyl; or (C1-C6alkyl, C2-C6alkenyl,2-C6quinil or3-C6cycloalkyl, each optionally substituted by one or more substituents independently selected from the group including halogen, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C2-C6alkoxycarbonyl,2-C6alkylsulphonyl,3-C6trialkylsilyl, and phenyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9; or

R2and R3can be combined with the nitrogen to which they relate, with formation of a ring containing 2-6 carbon atoms and optionally one additional atom selected from the group comprising nitrogen, sulfur and oxygen, such ring optionally substituted by one to four substituents, independently selected from the group comprising From1-C2alkyl, halogen, CN, NO2and C1-C2alkoxy;

each R4independently represents a C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cyclea the keel, With1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic,1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino or3-C6trialkylsilyl; or

each R4independently represents a phenyl, benzyl or phenoxy ring, each ring optionally substituted with one to three substituents, independently selected from R9;

each R5independently represents H, C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenosilanes, halogen, CN, CO2H, CONH2, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl is, With1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic,1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,2-C6alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl,3-C6dialkylaminoalkyl,3-C6trialkylsilyl; or

each R5independently represents a phenyl, benzyl, bentilee, phenoxy or 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system optionally substituted with one to three substituents, independently selected from R9; or

(R5)2together with the adjacent carbon atoms to which they are linked, may form-OCF2O-, -CF2CF2O - or-OCF2CF2O-;

each R6independently represents a C1-C6alkyl, C2-C6alkenyl,2-C6quinil, each optionally substituted by one or more substituents independently selected from the group including halogen, CN, C1-C4alkoxy, C2-C6alkoxyalkane,1-C4alkylthio, (C3-C6Tr is alkylsilane) 1-C2alkoxy, or R7;3-C6cycloalkyl; C2-C6alkylsulphonyl; C2-C6alkoxycarbonyl; C2-C6alkylaminocarbonyl; C3-C8dialkylaminoalkyl; C1-C4alkylsulfonyl; C1-C4halogenallylacetic or3-C9trialkylsilyl; or

each R6independently represents a phenyl ring or a 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9;

each R7independently represents a phenyl, benzyloxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9;

each R8independently represents H; C1-C6alkyl, C2-C6alkenyl,2-C6quinil, each optionally substituted by one or more substituents independently selected from the group including halogen, CN, C1-C4alkoxy, C1-C4alkylthio or R7;3-C6cycloalkyl; C2-C6alkylsulphonyl; C2-C6alkoxycarbonyl; C2-C6alkylaminocarbonyl; C3-C8dialkylaminoalkyl or3 -C9trialkylsilyl; or

each R8independently represents a phenyl ring or a 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9;

each R9independently represents a C1-C4alkyl, C2-C4alkenyl,2-C4quinil,3-C6cycloalkyl,1-C4halogenated,2-C4halogenoalkanes,2-C4halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2With1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,4-C8(alkyl)cyclooctylamino,2-C4alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl,3-C8dialkylaminoalkyl or3-C6trialkylsilyl; and n has a value from 1 to 4;

provided that when K is a-NR1C(=A)and A represents O or S, then L is other than-C(O)NR2- or-C(=S)NR2-.

The present invention also relates to a method of combat, one that is vodochnymi pests, comprising contacting bespozvonochnykh pest or its habitat with a biologically effective amount of the compounds of Formula I, its N-oxide or a suitable salt of such compounds (e.g., in the form of a composition described in this application). The present invention also relates to a method comprising contacting bespozvonochnykh pest or its habitat with a biologically effective amount of the compounds of Formula I, its N-oxide or a suitable salt or composition comprising a compound of Formula I, its N-oxide or a suitable salt and biologically effective amount of at least one additional compound or substance for combating invertebrate pests.

The present invention also relates to compositions for combating invertebrate pest comprising a biologically effective amount of the compounds of Formula I, its N-oxide or a suitable salt of such a compound and at least one additional component selected from the group comprising surfactants, solid diluents and liquid diluents. The present invention also relates to compositions comprising a biologically effective amount of the compounds of Formula I, its N-oxide or a suitable salt of such compounds and an effective amount of at least one stage is intellego biologically active compounds or substances.

Detailed description of the invention

In the above definitions, the term "alkyl", used either alone or in compound words such as "alkylthio" or "halogenated"includes alkyl straight or branched chain such as methyl, ethyl, n-propyl, isopropyl or the different butyl isomers, pentile or exile. "Alkenyl includes alkenes with a straight or branched chain, such as 1-propenyl, 2-propenyl and various isomers butenyl, pentenyl and hexenyl. "Alkenyl also includes a polyene, such as 1,2-PROPADIENE and 2,4-hexadienyl. "Quinil includes alkynes with a straight or branched chain, such as 1-PROPYNYL, 2-PROPYNYL, and the various isomers of butenyl, pentenyl and hexenyl. "Quinil" can also include fragments with multiple triple bonds, such as 2,5-hexadienyl. "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropoxy and various isomers of butoxy, pentox, hexyloxy. "Alkylthio" includes alkylthio group with a straight or branched chain, such as methylthio, ethylthio and various isomers of property, butylthio. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. "Trialkylsilyl" includes (CH3)3Si (CH3CH2)3Si and [(CH3)3C](CH3)2Si.

The term "aromatic" indicates that each of the ring atoms n is located essentially in the same plane and has a p-orbital, perpendicular to the plane of the ring, and where (4n+2)π electrons, when n is 0 or a positive integer, are associated with the ring, in accordance with the requirements of rule hukkala. The term "aromatic ring system" denotes fully unsaturated carbocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic. Aromatic carbocyclic ring or a condensed carbobicyclic ring systems include a fully aromatic carbocycle and carbocycle, in which at least one ring of a polycyclic ring system is aromatic (e.g., phenyl, naphthyl and 1,2,3,4-tetrahydronaphthyl). The term "non-aromatic carbocyclic ring" means a fully saturated carbocycle, as well as partially or fully unsaturated carbocycle, where the ring meets the requirements of rule hukkala. The term "hetero"as applied to the rings or ring systems, refers to a ring or ring system in which at least one ring atom is not carbon atom and which may contain from 1 to 4 heteroatoms, independently selected from the group comprising nitrogen, oxygen and sulfur, provided that each ring contains no more than 4 nitrogen atoms, not more than 2 oxygen atoms and not more than 2 sulfur atoms. The terms "GE is enormities ring or ring system" and "aromatic condensed heterobicyclic ring system" includes fully aromatic heterocycles and heterocycles, in which at least one ring of a polycyclic ring system is aromatic (where aromatic" means compliance with the requirements of rule hukkala). The term "non-aromatic heterocyclic ring or ring system" denotes fully saturated heterocycle, and a partially or fully unsaturated heterocycles, where neither one of the rings of the ring system does not meet the requirements of the hückel rule. Heterocyclic ring or ring system can be contacted through available carbon atom or nitrogen by replacement of a hydrogen by a specified carbon or nitrogen.

The term "halogen", either alone or as part of complex words, such as "halogenated"includes fluorine, chlorine, bromine or iodine. In addition, when used in compound words such as "halogenated"specified alkyl may be partially or completely replaced by halogen atoms that can be the same or different. Examples of "halogenoalkane" include F3C, ClCH2, CF3CH2and CF3CCl2. The terms "halogenoalkanes", "halogenoalkanes", "halogenoalkane" and the like are defined analogously to the term "halogenated". Examples of "halogenoalkane include (Cl)2C=CHCH2and CF3CH2CH=CHCH2. Examples of "halogenoalkane include HCCCHCl, CF3CC, CCl3CC and FCH2CCCH2. Examples of "halo is analsexy" include CF 3O CCl3CH2O, HCF2CH2CH2O and CF3CH2O.

Examples of "alkylcarboxylic" include C(O)CH3C(O)CH2CH2CH3and

C(O)CH(CH3)2. Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O) (CH3)2CHOC(=O) and various butoxy or phenoxycarbonyl isomers. Examples of "alkylaminocarbonyl" include CH3NHC(=O), CH3CH2NHC(=O), CH3CH2CH2NHC(=O) (CH3)2CHNHC(=O) and the various isomers of butylamino or intramyocardial. Examples of "dialkylaminoalkyl include (CH3)2NC(=O) (CH3CH2)2NC(=O), CH3CH2(CH3)NC(=O), CH3CH2CH2(CH3)NC(=O) and (CH3)2CHN(CH3)C(=O).

The total number of carbon atoms in the group Deputy indicated subscripts "Ci-Cj"where i and j denote integers from 1 to 8. For example, With1-C3alkylsulfonyl includes values from methylsulfonyl to propylsulfonyl; C2alkoxyalkyl means CH3OCH2; C3alkoxyalkyl means, for example, CH3CH(OCH3), CH3OCH2CH2or CH3CH2OCH2; and (C4alkoxyalkyl refers to the various isomers of an alkyl group, substituted alkoxygroup, where the total number of carbon atoms of RA is but four, examples of which include CH3CH2CH2OCH2and CH3CH2OCH2CH2.

In the above definitions, when the compound of Formula I contains a heterocyclic ring, all the substituents are associated with this ring through any available carbon atom or nitrogen by replacement of a hydrogen by a specified carbon or nitrogen.

When the connection is substituted by the Deputy indicated that the number of such substituents can exceed 1, the said substituents (when they exceed 1) are independently selected from the group of defined substituents. In addition, when specified limits, for example, (R)i-jthen the number of the substituents may be selected from the integers from i to j, inclusive.

The term "optionally substituted" means that the group is either unsubstituted or substituted. The term "optionally substituted one to three substituents", etc. means that from one to three of the available positions in the group may be substituted. When a group contains a Deputy, which can be hydrogen, for example, R1or R5then, if the Deputy means hydrogen, it should be clear that this is equivalent to the fact that the specified group is unsubstituted.

Compounds of the present invention can exist as one or more stereoisomers. The difference is these stereoisomers include enantiomers, the diastereomers, atropisomers and geometric isomers. The specialist in this area should be clear that one stereoisomer may be more active and/or can demonstrate the best action when the enrichment compared with the other(s) stereoisomer(s) or when separated from the other(s) stereoisomer(s). In addition, the specialist should be well-known methods of separation, enrichment and/or selective receipt of stereoisomers. Therefore, the compounds of the present invention may be present in the form of a mixture of stereoisomers, individual stereoisomers or in the form of optically active forms. Some compounds of the present invention can exist as one or more tautomers, and all tautomeric forms of these compounds are part of the present invention. Therefore, the compounds of the present invention may be present as a mixture of tautomers, or as individual tautomers.

The present invention includes compounds selected from compounds of the Formula I, their N-oxides and suitable salts. The person skilled in the art should understand that not all nitrogen-containing heterocycles can form N-oxides as nitrogen requires a separate pair of electrons for oxidation in the oxide; the expert can differentiate between the nitrogen gets Rosicky, which can form N-oxides. The specialist in this area should also be clear that tertiary amines can form N-oxides. Methods of synthesis for the preparation of N-oxides of heterocycles and tertiary amines are well known to specialists in this field, including the oxidation of heterocycles and tertiary amines peroxy acids, as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkylhydroperoxides, such as tert-butylhydroperoxide, perborate sodium and dioxirane, such as dimethyldioxirane. Such methods of obtaining N-oxides have been described in detail and discussed in the literature, see for example: T. L. Gilchrist in Comprehensive organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tišler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, Vol. 3, pp 18-19, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, Vol. 43, pp 139-151, A. R. Katritzky, Ed., Academic Press; M. Tišler and B. Stanovnik in Advances in Heterocyclic Chemistiy, Vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistiy, Vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.

Salts of the compounds of the present invention include acid additive salts of inorganic or organic acids, such as Hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, Winne the I, 4-toluensulfonate or valeric acid. Salts of the compounds of the present invention also include salts formed with organic bases (e.g. pyridine, ammonia and triethylamine), or salts formed with inorganic bases (e.g., hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium)when the compound contains an acidic group such as carboxylic acid or phenol.

As described above, each J independently represents a phenyl ring, a 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed carbobicyclic or heterobicyclic ring system, each ring or ring system substituted by one to four R5. Examples of phenyl substituted by one to four R5is the ring illustrated as U-l in View 1 below, where Rvis an R5and r is an integer from 1 to 4. Examples of aromatic 8-, 9 - or 10-membered condensed carbobicyclic ring system substituted by one to four R5include naftalina group, shown as U-85 in View 1, and 1,2,3,4-tetrahydronaphthalene group, shown as U-89 in View 1, where Rvis an R3and r is an integer from 1 to 4. Examples of 5 - or 6-membered heteroatom the political ring, substituted by one to four R5include the rings U-2 through U-53, shown in View 1, where Rvis an R5and r is an integer from 1 to 4. It should be noted that illustrated below J-l through J-4 also mean a 5 - or 6-membered heteroaromatic ring. It should be noted that the U-2 U-20 are examples J-l, U-21 and U-35 U-40 are examples of J-2, U-41 U-48 are examples of J-3 and U-49 U-53 are examples of J-4. Examples of aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring systems substituted with one to four R5include U-54 U-84, shown in View 1, where Rvis an R5and r is an integer from 1 to 4.

Despite the fact that the groups Rvshown in structures with U-l U-90, it should be noted that when they are optional substituents, they may not be present. It should be noted that when Rvrepresents H, at his accession to the atom is similar to that specified atom is nazimaxanum. The nitrogen atoms that require substitution to fill their valence, replaced with H, or Rv. It should be noted that some of U groups can be substituted only less than 4 groups of Rv(for example, U-4, U-15, U-l8 U-21 and U-32 U-34 can be replaced by only one Rv. It should be noted that when the attachment point between the groups (Rv)rand U is shown as a free (mobile), (Rv)rmay accede to an available carbon atom U group. It should be noted that when the attachment point U of the group is shown as a free (mobile), U group may be attached to the rest of the Formulas I through any available carbon atom U group by replacement of a hydrogen atom.

View 1

As indicated above, some groups of R1, R3, R6and R8optionally can be substituted by one or more substituents. The term "optionally substituted" in connection with these Rwgroups (where w is 1, 3, 6, or 8) refers to the R groups that are not substituted or having at least one non-hydrogen Deputy. Examples of the optionally substituted Rwgroups are groups, optionally substituted by replacement of the hydrogen at the carbon atom of the group Rwone or more (up to the total number of hydrogen atoms available for substitution in any particular Rwthe group substituents, independently selected from the substituents listed in the section "Summary of isana of the invention" above. Although such deputies and lists, it should be noted that they do not need to be present since they are optional substituents. Particularly noteworthy is the Rwthe group, which are unsubstituted. Also important are Rvgroup, substituted by substituents from one to five. Also important are the Rwgroup, substituted by one Deputy.

As indicated above, R3may submit C1-C6alkyl, C2-C6alkenyl, C2-C6quinil or C3-C6cycloalkyl, each optionally substituted by (among other things) phenyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9. Examples of such rings, which substituents include the rings represented as rings U-l (phenyl), U-2 through U-53 (5 - or 6-membered heteroaromatic ring) and U-86 (phenoxy), shown in View 1 above, where Rvis an R9and r is an integer from 1 to 3.

As described above, each R4can independently represent (among other things) phenyl, benzyl or phenoxy ring, each ring optionally substituted with one to three substituents, independently selected from R9. Examples of such rings, I have which substituents, include rings represented as rings U-l (phenyl), U-87 (benzyl) and U-86 (phenoxy), shown in View 1 above, where Rvis an R9and r is an integer from 1 to 3.

As described above, each R5can independently represent (among other things) phenyl, benzyl, bentilee, phenoxy or 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system optionally substituted with one to three substituents, independently selected from R9. Examples of such rings, which substituents include the rings represented as rings U-l (phenyl), U-87 (benzyl), U-8S (benzoyl), U-86 (phenoxy), U-2 through U-53 (5 - or 6-membered heteroaromatic ring) and U-54 U-84 (aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system), shown in View 1 above, where Rvis an R9and r is an integer from 1 to 3.

As described above, each R6and each R8can independently represent (among other things) a phenyl ring or a 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9. Examples of such R6and R groups include the rings illustrated as rings U-l (phenyl) and U-2 through U-53 (5 - or 6-membered heteroaromatic ring), as shown in View 1 above, where Rvis an R9and r is an integer from 1 to 3.

As described above, each R7can independently represent phenyl, benzyloxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9. Examples of such R7groups include rings represented as rings U-l (phenyl), U-90 (benzyloxy) and U-2 through U-53 (5 - or 6-membered heteroaromatic ring), as shown in View 1 above, where Rvis an R9and r is an integer from 1 to 3.

The preferred compounds, because of their better activity and/or ease of synthesis are the following:

A preferred group 1. The compounds of formula I, where K represents a-NR1C(=A)and A is O.

A preferred group 2. The compounds of formula I, where L represents-C(-B)NR2and B is O.

A preferred group 3. The Preferred compounds of the group 1 or the preferred group 2, where

J is a phenyl ring or a 5 - or 6-membered heteroaromatic ring selected from the group including J-l, -2, J-3 and J-4, wherein each ring is substituted by one to four substituents independently selected from R5

Q represents O, S or NR5;

W, X, Y and Z independently represent N or CR5provided that in J-3 and J-4 at least one of W, X, Y or Z represents N;

R1represents H, C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C2-C6alkylaryl or C2-C6alkoxycarbonyl;

R2represents H, C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C2-C6alkylaryl or C2-C6alkoxycarbonyl;

R3represents H; or C1-C6alkyl, C2-C6alkenyl, C2-C6quinil or C3-C6cycloalkyl, each optionally substituted by one or more substituents independently selected from the group including halogen, CN, C1-C6alkoxy, C1-C2alkylthio, C1-C2alkylsulfonyl and C1-C2alkylsulfonyl;

one of the groups R4attached to the rest of the formula I or in position 2, or position 5 of the phenyl ring, and the specified R4represents a C1-C 4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes or C1-C4halogenallylacetic;

each R5independently represents H, C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic, C2-C4alkoxycarbonyl, C2-C6alkylaminocarbonyl or C3-C8dialkylaminoalkyl; or

each R5independently represents a phenyl, benzyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R9; or

(R5)2together with the adjacent carbon atoms to which they are linked, form a-OCF2O-, -CF2CF2O - or-OCF2CF2O-;

each R6independently represents a C1-C6 alkyl, C2-C6alkenyl, C2-C6quinil, each optionally substituted by one or more substituents independently selected from the group including halogen, CN, C1-C4alkoxy, C1-C4alkylthio and R7; and n has a value of 1 or 2.

From the Preferred group 3 are of special importance in connection, where K represents a-NR1C(=O) -, and L represents-C(GR6)=N - or-SO2NR2-. Also of particular importance are compounds of Preferred 3 where K represents a-NR1C(=O) -, and L represents-C(=O)-. Also of particular importance are compounds of Preferred 3 where L represents-C(=O)NR2and K represents-N=C(GR6)- or-NR1SO2-.

A preferred group 4. The Preferred compounds of group 3, where

R1and R2each, independently, represents H or C1-C4alkyl;

R3represents a C1-C4alkyl, optionally substituted with halogen, CN, OCH3or S(O)pCH3;

each R5independently represents H, C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl C 1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic or C2-C4alkoxycarbonyl, C2-C6alkylaminocarbonyl or C3-C8dialkylaminoalkyl; or phenyl, benzyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with halogen, CN, NO2C1-C4the alkyl, C2-C4alkenyl, C2-C4the quinil, C3-C6cycloalkyl, C1-C4halogenation, C1-C4alkoxy or C1-C4halogenoalkane; provided that one of R5with the J at the position ortho to K and at least one R5is other than H, G represents O or S; and

p is 0, 1 or 2.

A preferred group 5. The Preferred compounds of group 4, where J is a phenyl, pyrazol, pyrrole, pyridine or pyrimidine ring, each substituted with one R5associated with the J at the position ortho to K, and, optionally, one or two additional R5.

A preferred group of 6. The Preferred compounds of group 5, where

R1and R2both represent H;

one R4attached to the rest of the formula I in position 2 of the phenyl ring ortho relative to the K-J fragment and selected from groups who, including C1-C3alkyl, CF3, OCF3, OCHF2, S(O)pCF3, S(O)pCHF2and halogen, and, optionally, the second R4attached in position 4 of the phenyl ring, a pair of relatively K-J fragment selected from the group comprising halogen, C1-C3alkyl and C1-C3halogenated.

A preferred group of 7. The Preferred compounds of group 6, where

J represents pyrazol or pyrrole ring, selected from the group including J-5, J-6, J-7, J-8, J-9 and J-10, with each ring substituted R5and optionally substituted by an R10and R11;

R5represents H, C1-C4alkyl, C1-C4halogenated, or

V represents N, CH, CF, CC1, CBr or CI;

each R10and each R12independently represent H, C1-C6alkyl, C3-C6cycloalkyl, C1-C6halogenated, halogen, CN, C1-C4alkoxy, C1-C4halogenoalkane or C1-C4allogenicity; and

R11represents H, C1-C6alkyl, C1-C6halogenated, C3-C6alkenyl, C3-C6halogenoalkanes, C3-C6quinil or C3-C6halogenoalkanes.

Be aware that Rsup> 10and R11are subgroups of the group of substituents R5. Also be aware that when R12is other than H, it is a subgroup of the group of substituents R9and that the atoms of F, Cl, Br or I, are included in the definition of group V, also are a subgroup of the group of substituents R9. It should be noted that the group defined for R5associated with J through a connection indicated by a wavy line.

A preferred group of 8. The Preferred compounds of group 7, where V represents n

A preferred group 9. The Preferred compounds of group 7, where V represents CH, CF, CCl or CBr.

A preferred group of 10. The Preferred compounds of group 8 or Preferred group 9, where

R12represents H, C1-C4alkyl, C1-C4halogenated, halogen or CN;

R10represents H, CH3, CF3, OCH2CF3, OCHF2or halogen; and

R11represents CH2CF3, CHF2or CF3.

A preferred group 11. The Preferred compounds of group 10, where J is replaced with an R5and optionally substituted by an R10represents the J-5; R12represents Cl or Br; and R10represents halogen, OCH2CF3, OCHF2or CF3.

A preferred group 1. The Preferred compounds of group 10, where J is replaced with an R5and optionally substituted by an R11represents the J-6; R12represents Cl or Br; and R11represents CH2CF3, CHF2or CF3.

A preferred group 13. The Preferred compounds of group 10, where J is replaced with an R5and optionally substituted by an R11represents the J-7; R12represents Cl or Br; and R11represents CH2CF3, CHF2or CF3.

A preferred group 14. The Preferred compounds of group 10, where J is replaced with an R5and optionally substituted by an R10represents the J-8; R12represents Cl or Br; and R10represents halogen, OCH2CF3, OCHF2or CF3.

A preferred group of 15. The Preferred compounds of group 10, where J is replaced with an R5and optionally substituted by an R10and R11is a J-9; R12represents Cl or Br; R10represents halogen, OCH2CF3, OCHF2or CF3; and R11represents CH2CF3, CHF2or CF3.

A preferred group 16. The Preferred compounds of group 10, where J is replaced with an R5and optionally substituted by an R11represents the J-10; Rl2isone Cl or Br; and R11represents CH2CF3, CHF2or CF3.

Most preferred is a compound of formula I, which is a

1-(3-Chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]-sulfonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide.

The importance of the compounds of formula If, their N-oxides and agricultural acceptable salt

where

J is a phenyl ring, naftalina ring system, a 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system are optionally substituted by 1-4 substituents R5;

K represents a-NR1C(=A)-, -N=C(GR6)- or-NR1SO2-;

L represents-C(-B)NR2-, -C(GR6)=N-, -SO2NR2-or

-C(=O)-;

A and B independently represent O, S, NR6, NOR6, NN(R6)2, S=O, N-CN or N-NO2;

each G independently represents O, S or NR6;

R1represents H; or C1-C6alkyl, C2-C6alkenyl, C2-C6quinil or C3-C6cycloalkyl, each optionally substituted by one or more substituents selected from the group comprising halog is h, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C2-C4alkoxycarbonyl, C1-C4alkylamino, C2-C8dialkylamino and C3-C6cyclooctylamino; or

R1represents a C2-C6alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl or C3-C8dialkylaminoalkyl;

R2represents H, C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, C3-C6cycloalkyl, C1-C4alkoxy, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C2-C6alkoxycarbonyl or C2-C6alkylsulphonyl;

R3represents H; C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, C3-C6cycloalkyl, each optionally substituted by one or more substituents selected from the group including halogen, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C2-C6alkoxycarbonyl, C2-C6alkylsulphonyl, C3-C6trialkylsilyl, or phenyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from the group comprising C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C1-C4halogenated, C2-C4halogenoalkanes, C2-C4halogenoalkanes, C3-C6halogenosilanes, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C3-C6(alkyl)cyclooctylamino, C2-C4alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or C3-C6trialkylsilyl; C1-C4alkoxy, C1-C4alkylamino; C2-C8dialkylamino; C3-C6cyclooctylamino; C2-C6alkoxycarbonyl or C2-C6alkylsulphonyl; or

R2and R3taken together with the nitrogen atom to which they are linked, form a ring containing 2 to 6 atoms of carbon and optionally one additional atom of nitrogen, sulfur, or is ikorodu, when mentioned this ring is optionally substituted by 1-4 substituents selected from the group comprising C1-C2alkyl, halogen, CN, NO2and C1-C2alkoxy;

each R4independently represents H, C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, C3-C6cycloalkyl, C1-C6halogenated, C2-C6halogenoalkanes, C2-C6halogenoalkanes, C3-C6halogenosilanes, halogen, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, or C3-C6trialkylsilyl; or

each R4independently represents a phenyl, benzyl or phenoxy, each optionally substituted C1-C4the alkyl, C2-C4alkenyl, C2-C4the quinil, C3-C6cycloalkyl, C1-C4halogenation, C2-C4halogenation, C2-C4halogenoalkanes, C3-C6halogencyclization, halogen, CN, NO2 C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C3-C6(alkyl)cyclooctylamino, C2-C4alkylcarboxylic, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or C3-C6trialkylsilyl;

each R5independently represents H, C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, C3-C6cycloalkyl, C1-C6halogenated, C2-C6halogenoalkanes, C2-C6halogenoalkanes, C3-C6halogenosilanes, halogen, CN, CO2H, CONH2, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C2-C6alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl is l, C3-C8dialkylaminoalkyl, C3-C6trialkylsilyl; or

each R5independently represents a phenyl, benzyl, bentilee, phenoxy, 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring optionally substituted with one to three substituents, independently selected from the group comprising C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C1-C4halogenated, C2-C4halogenoalkanes, C2-C4halogenoalkanes, C3-C6halogenosilanes, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C3-C6(alkyl)cyclooctylamino, C2-C4alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or C3-C8trialkylsilyl; or

(R5)2together with the adjacent carbon atoms to which they are linked, form a-OCF2O-, -CF2CF2O - or-OCF2CFsub> 2O-;

each R6independently represents a C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, optionally substituted with halogen, CN, C1-C4alkoxy, C1-C4alkylthio or R7; C3-C6cycloalkyl; or C2-C4alkoxycarbonyl; or

each R6independently represents a phenyl ring or a 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from the group comprising C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C1-C4halogenated, C2-C4halogenoalkanes, C2-C4halogenoalkanes, C6-C6halogenosilanes, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C3-C6(alkyl)cyclooctylamino, C2-C4alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or C3-C6trialkylsilyl;

each R7illegal is ASIMO represents a phenyl ring or a 5 - or 6-membered heteroaromatic ring, in addition, each ring optionally substituted with one to three substituents, independently selected from the group comprising C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C1-C4halogenated, C2-C4halogenoalkanes, C2-C4halogenoalkanes, C3-C6halogenosilanes, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C3-C6(alkyl)cyclooctylamino, C2-C4alkylsulphonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or C3-C6trialkylsilyl; and

n has a value from 1 to 4;

provided that when K is a-NR1C(=A)and A represents O or S, then L is non -

-C(=O)NR2- or-C(=S)NR2-.

Also important are the selected compounds of formula I.

Selected group A. the compounds of formula I, where K represents a-NR1C(=A)and A is O.

Selected group B. the compounds of formula I, where L represents-C(=B)NR2and B represents Soboh the O.

Selected group C. Compounds Selected from group B or group Selected C, where

J is a phenyl ring or a 5 - or 6-membered heteroaromatic ring selected from the group including J-l, J-2, J-3 and J-4, with each ring J optionally substituted by 1-3 substituents R5

Q represents O, S or NR5;

W, X, Y and Z independently represent N or CR5provided that in J-3 and J-4 at least one of W, X, Y or Z represents N;

R1represents H, C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C2-C6alkylaryl or C2-C6alkoxycarbonyl;

R2represents H, C1-C4alkyl, C2-C4alkenyl, C2-C4quinil, C3-C6cycloalkyl, C2-C6alkylaryl or C2-C6alkoxycarbonyl;

R3represents a C1-C6alkyl, C2-C6alkenyl, C2-C6quinil or C3-C6cycloalkyl, each optionally substituted by one or more substituents selected from the group including halogen, CN, C1-C2alkoxy, C1-C2alkylthio, C1-C2alkylsulfonyl and C1-C2alkylsulfonyl;

one g of the UPP R 4attached to the phenyl ring in position 2 or position 5, and the specified R4represents a C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes or C1-C4halogenallylacetic;

each R5independently represents H, C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic or C2-C4alkoxycarbonyl, C3-C8dialkylaminoalkyl; or

each R5independently represents a phenyl, benzyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted C1-C4the alkyl, C2-C4alkenyl, C2-C4the quinil, C3-C6cycloalkyl, C1-C4halogenation, C2-C4halogenation, C2-C4 halogenoalkanes, C3-C6halogencyclization, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4alkylamino, C2-C8dialkylamino, C3-C6cyclooctylamino, C3-C6(alkyl)cyclooctylamino, C2-C4alkylcarboxylic, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C3-C8dialkylaminoalkyl or C3-C6trialkylsilyl; or

(R5)2together with the adjacent carbon atoms to which they are linked, form a-OCF2O-, -CF2CF2O - or-OCF2CF2O-;

each R6independently represents a C1-C6alkyl, C2-C6alkenyl, C2-C6quinil, optionally substituted with halogen, CN, C1-C4alkoxy, C1-C4alkylthio or R7; and

n has a value from 1 to 2.

Important are compounds Selected group C, where K represents a-NR1C(=O) -, and L represents-C(GR6)=N - or-SO2NR2-. Also important are compounds Selected group C, where L represents-C(=O)NR2and K is a

-N=C(GR6)- or-NR1SO2-.

The selected group is as D. Compounds Selected group C, where

R1represents H or C1-C4alkyl;

R2represents H or C1-C4alkyl;

R3represents a C1-C4alkyl, optionally substituted with halogen, CN, OCH3or S(O)pCH3;

one group R5attached to the J at the position ortho relative to K, and the specified R5represents a C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic or C2-C4alkoxycarbonyl; C3-C8dialkylaminoalkyl or phenyl, benzyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with halogen, CN, NO2C1-C4the alkyl, C2-C4alkenyl, C2-C4the quinil, C3-C6cycloalkyl, C1-C4halogenation, C1-C4alkoxy or C1-C4halogenoalkane;

and an optional second group R5independently represents a C1-C4alkyl, C1-C4halogen is lcil, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane, C1-C4alkylthio, C1-C4alkylsulfonyl, C1-C4alkylsulfonyl, C1-C4allogenicity, C1-C4halogenacetylenes, C1-C4halogenallylacetic or C2-C4alkoxycarbonyl; C3-C8dialkylaminoalkyl or phenyl, benzyl or 5 - or 6-membered heteroaromatic ring, each ring optionally Samusenko halogen, CN, NO2C1-C4the alkyl, C2-C4alkenyl, C2-C4the quinil, C3-C6cycloalkyl, C1-C4halogenation, C1-C4alkoxy or C1-C4halogenoalkane;

G represents O or S; and

p is 0, 1 or 2.

Selected group that is Compounds Selected group D, where J is a phenyl, pyrazole, pyrrole, pyridine or pyrimidine, each substituted with one R5associated with the J at the position ortho with respect To, and the second, optional, R5.

Selected group F. Connection of the Selected group E, where R1and R2each represents H;

one R4attached in position 2 (ortho relative to the K-J fragment selected from the group comprising C1-C3alkyl, CF3, OCF3, OCHF2, S(O)pC 3, S(O)pCHF2and halogen, and an optional second R4attached in position 4 pair regarding K-J fragment selected from the group comprising halogen, C1-C3alkyl and C1-C3halogenated.

Selected group F. Connection of the Selected group E, where

J represents a J-1;

Q represents NR5a;

X represents N or CH;

Y represents CH;

Z represents CR5b;

R5arepresents phenyl or 2-peregrinae ring, substituted with one or two substituents selected from the group comprising halogen, C1-C4alkyl, C1-C4halogenated or C1-C4halogenoalkane; and

R5brepresents a halogen or CF3.

To obtain the compounds of Formula I can be used one or more of the following methods and options are illustrated in the diagrams 1-33. The values of A, B, J, R1, R2, R3, R4, R5, R6, R7, R8, R9and n in the following Formula 1-88 mentioned above in the section "Brief description of the invention". Compounds of formulas Ia-e, 2a-b, 4a-s, 5a-d are subgroups of compounds of Formulas 1, 2, 4, and 5.

The compounds of formula Ia (where K represents NR1C(=O)) can be obtained by combining an amine of Formula 2 with an acid chloride of the acid of Formula 3 in PR is the presence of an acid acceptor, resulting in the receive connection of the Formula Ia. Typical acid acceptors include amine bases such as triethylamine, diisopropylethylamine and pyridine; other acceptors include hydroxides such as sodium hydroxide or potassium hydroxide, and carbonates such as sodium carbonate or potassium. In some cases it is useful to use the acid acceptors for polymer substrates, such as associated with the polymer diisopropylethylamine and associated with the polymer dimethylaminopyridine. The reaction mix is carried out in a suitable inert solvent such as tetrahydrofuran, dioxane, diethyl ether or dichloromethane, getting anilide Formula Ia. At the next stage amides of Formula Ia can be converted to thioamides of Formula Ib using a variety of standard agents transfer tigraphy, including pentasulfide phosphorus and reagent Lawesson.

An alternative method of preparing compounds of Formula Ia includes the combination of an amine of Formula 2 with an acid of Formula 4 in the presence of the agent degidrirovaniya, such as dicyclohexylcarbodiimide (DCC). Reagents on a polymer substrate is also useful in this way, for example, associated with the polymer cyclohexylcarbodiimide. Methods of synthesis are illustrated in Schemes 1 and 2 are merely representative examples of the ways ispolzuemykh obtain compounds of the Formula I, as in the literature on the synthesis of very widely described this type of reaction.

The person skilled in the art should be understood that the anhydrides of the acids of Formula 3 can be obtained from the acids of Formula 4 different well known methods. For example, the anhydrides of the acids of Formula 3 can be easily obtained from the carboxylic acids of Formula 4 by reacting carboxylic acid 4 with thionyl chloride or oxalylamino in an inert solvent, such as toluene or dichloromethane, in the presence of catalytic amounts of N,N-dimethylformamide.

Amines of the Formula 2 are usually easily obtained from the corresponding nitro compounds of Formula 5 by catalytic hydrogenation of the nitro group. Typical methods include restoration using hydrogen in the presence of a metal catalyst such as palladium on coal or palladium oxide, and hydroxyl solvent, such as ethanol or isopropanol. They can also be obtained by recovery using zinc in acetic acid. Such techniques are well described in the chemical literature. The substituents R1such as alkyl, substituted alkyl and the like, as a rule, you can enter at this stage through usually the preferred method of rehabilitation amine alkylation. Commonly used procedure before the hat is the Association of aniline 2A with an aldehyde in the presence of a reducing agent, such as cyanoborohydride sodium, to obtain the compounds of Formula 2B, where R1represents alkyl, alkenyl, quinil or their substituted derivatives.

The compounds of formula Ic (where K is an N=(GR6) can be obtained by the interaction of amidoalkylation Formula 6 with sulfur, oxygen and nitrogen nucleophiles of Formula 7. Typically the reaction is carried out in the presence of a base such as tertiary amine or hydroxide of an alkali metal.

The compounds of Formula 6 can be obtained from compounds of Formula Ia by reacting a suitable halogenation agent such as pentachloride phosphorus, phosphorus oxychloride, thionyl chloride or triphenylphosphine and carbon tetrachloride.

Alternatively, the compounds of Formula Id (where K is a N=C(SR6)), where R6represents an alkyl or substituted alkyl group, can be obtained from compounds of Formula Ib interaction with alkylhalogenide formula 8, optionally in the presence of a base such as tertiary amine or alkoxide of an alkali metal.

The compounds of formula 1E (where K represents NR1SO2) can be obtained by reacting an amine of Formula 2 with sulfonyl is the home of Formula 9 in the presence of an acid acceptor. Typical acid acceptors include amine bases such as triethylamine, diisopropylethylamine and pyridine; other acceptors include hydroxides such as sodium hydroxide or potassium hydroxide, and carbonates such as sodium carbonate or potassium. In some cases it is useful to use the acid acceptors for polymer substrates, such as associated with the polymer diisopropylethylamine and associated with the polymer dimethylaminopyridine.

Nitro compounds of Formula 5A (where L represents C(=O)NR2) can be easily obtained from commercially available 2-nitrobenzoic acids (Scheme 8). Here you can apply a typical method of the formation of amides. Such methods include direct dehydrative the combination of acids of Formula 10 with amines of the Formula 11 using, for example, DCC, and the conversion of the acid into an activated form, such as acid chlorides or anhydrides of the acids with subsequent coupling with amines to obtain amides of Formula 5A. In the chemical literature described this type of reaction. Amides of Formula 5A can be easily converted to thioamides of Formula 5b using commercially available agents transfer tigraphy, such as pentasulfide phosphorus and reagent Lawesson.

Nitro compounds of Formula 5C (where L represents C(GR6)=N) by the learning of the compounds of Formula 5A through imidoilchloride Formula 12 ways such is illustrated in Schemes 4 and 5.

Nitro compounds of Formula 5D (where L represents the SO2NR2) can be obtained from amines of Formula 13 by diazotization using such reagents as sodium nitrite or alkylated, and interaction with sulfur dioxide in the presence of a copper catalyst (see, for example, Courtin, A. Helv.Chim.Acta, 1976, 59, 379-387) with subsequent interaction with amines of the Formula 11 (see Scheme 8). The synthesis of amines of Formula 13 are well known in the prior art.

Benzoic acid of Formula 4A (compound of Formula 4, where J is an optionally substituted phenyl ring) is well known from the prior art. Getting some heterocyclic acids of Formula 4 are illustrated on figures 11-16. Various heterocyclic acids and methods for their preparation are described in International patent application WO 98/57397.

The synthesis of representative pyridine acids (4b) is shown in figure 11. This procedure includes the known synthesis of pyridines from complex β-ketoesters and 4-aminobutanol (17). The group of substituents R5(C) and R5(d) include, for example, alkyl and halogenated.

A representative synthesis of pyrimidine acid (4C) is shown in figure 12. This procedure involves known the initial synthesis of pyrimidines from vinyliden-β -ketoesters (20) and amidino. The group of substituents R5(C) and R5(d) include, for example, alkyl and halogenated.

The synthesis of representative peratrovich acid (4d-g) are presented on figures 13-16. Synthesis of 4d in figure 13 includes as a key stage of the introduction of the substituent R5(C) via alkylation of pyrazole. The alkylation agent R5(C)-Lg (where Lg represents a removable group, such as Cl, Br, I, sulfonates such as p-toluensulfonate or methanesulfonate, or sulfates, such as-SO2OR5(C)) includes the group R5(C), such as C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenosilanes,2-C6alkylsulphonyl,2-C6alkoxycarbonyl,3-C8dialkylaminoalkyl,3-C6trialkylsilyl; or phenyl, benzyl, bentilee, 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system are optionally substituted. As a result of oxidation of a methyl group to get pyrazolylborate KIS the GTC. Some of the more preferred R5(d) group include halogenated.

Scheme 13

Some pyrazolone acid of Formula 4d can be obtained through metallation and carboxylation pyrazoles of formula 26 as a key stage (Scheme 14). R5(C) the group introduced a method similar to that described in Scheme 13, i.e. through alkylation by means of alkylation agent R5(C). Representative R5(d) groups include, for example, cyano and halogenated.

This procedure is particularly useful to obtain 1-(2-pyridinyl)pyrazolylborate acids of Formula 4E belonging to the preferred group J-5, where R5represents a substituted 2-pyridinoline ring as shown in Scheme 15. The interaction of the pyrazole of Formula 27 with 2,3-dehalogenation Formula 23 provides a good yield of 1-pyridylacetate Formula 28 with good specificity against the desired stereochemistry. In the metallation of 28 diisopropylamide lithium (LDA) followed by quenching of the lithium salt with carbon dioxide receive 1-(2-pyridinyl)pyrazolylborate acid of Formula 4E.

Other pyrazoles of Formula 4d can be obtained by the reaction of optionally substituted phenylhydrazine of Formula 30 with pyruvate Formula 29 with education is receiving complex peratrovich esters of Formula 31 (Scheme 16). As a result of hydrolysis of ester receive pyrazolone acid 4D. This procedure is particularly useful for producing compounds where R5(c) is optionally substituted phenyl and R5(d) represents halogenated.

Pyrazolone acid of Formula 4d can be obtained through a 3+2 cycloaddition suitably substituted nitrilimines Formula 32 or substituted propiolate Formula 33, or acrylates of Formula 34 (Scheme 17). Cycloaddition with acrylates requires additional oxidation of the intermediate pyrazoline to the pyrazole. Hydrolysis of ester of the Formula 31 gives pyrazolone acid 4d. Preferred aminoglucoside for this reaction include triptoreline (35) and kinodynamic (36). Compounds such as 35, are known (J.Heterocycl.Chem. 1985, 22(2), 565-8). Compounds such as 36, may be easily obtained by the known methods (Tetrahedron Letters 1999, 40, 2605). These techniques are particularly useful for producing compounds where R5(c) is optionally substituted phenyl and R5(d) represents halogenated or bromine.

Source pyrazoles of Formula 25 are known compounds or may be obtained by known methods. The pyrazole of Formula 25A (compound of Formula 25, where R5(d) represents CF3)can be obtained by means described in the literature (J.Fluorine Chem. 1991, 53(1), 61-70). The pyrazoles of the Formula 25b (compound of Formula 25, where R5(d) represents Cl or Br) can be obtained by methods described in the literature (Chem.Ber. 1966, 99(10), 3350-7). A useful alternative method for obtaining compounds 25b presented in figure 18. Metallation of sulfamoylbenzoyl Formula 37 n-butyllithium with subsequent direct halogenoalkanes anion or hexachlorethane (R5(d), which represents Cl), or 1,2-dibromotetrachloroethane (R5(d), which represents Br) gives a halogenated derivative of Formula 38A. The reaction removal sulfamoyl group triperoxonane acid (TFA) flows pure and results pyrazoles of the Formula 25s with a good yield. The person skilled in the art should understand that the Formula 25C is tautomer Formula 25b.

Pyrazolylborate acid of Formula 4f, where R10is a CF3you can get way presented in figure 19.

The interaction of the compounds of Formula 38b, where R12represents a C1-C4alkyl, with a suitable base in a suitable organic solvent gives cyklinowanie product Formula 39 after neutralization of the acid, such as acetic KIS the PTA. A suitable base may be, for example (but without limitation), sodium hydride, tert-piperonyl potassium, damsel sodium (CH3S(O)CH2-Na+), carbonates or hydroxides of alkali metals (such as lithium, sodium or potassium), fluorides or hydroxides of tetraalkyl (for example, methyl, ethyl or butyl)ammonium or 2-tert-Butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-datafactory. Suitable organic solvent may be, for example (but without limitation), acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethyl sulfoxide or N,N-dimethylformamide. The cyclization reaction is usually carried out at a temperature in the range from 0 to 120aboutC. the Effect of solvent, base, temperature and time add interrelated, and the choice of reaction conditions is important to obtain the minimum formation of by-products. The preferred base is tetrabutylammonium fluoride.

The dehydration of compounds of Formula 39 with obtaining the compounds of Formula 40 and then converting the functional group of ester carboxylic acid group, carboxylic acid gives compound of Formula 4f. Dehydration carried out by treatment with a catalytic amount of a suitable acid. Such catalytic acid may, for example, to represent (but without to the any restrictions) sulfuric acid. The reaction is usually carried out using an organic solvent. The person skilled in the art should understand that dehydration reaction can be performed in a wide range of solvents at a temperature ranging from about 0 to 200aboutC, more preferably, from about 0 to 100aboutC. For dehydration, shown in figure 19, it is preferable solvent includes acetic acid, and the temperature is about 65aboutC. esters of carboxylic acids can be converted into compounds of carboxylic acids in a variety of ways, including nucleophilic cleavage in anhydrous conditions or hydrolytic methods, including the use of either acids or bases (for a review of these methods see T.W.Greene and P.G.M.Wuts, Protective Groups in Organic Synthesis, 2nded., John Wiley & Sons, Inc., New York, 1991, pp. 224-269). For the method presented in Scheme 19, the preferred are base catalyzed hydrolytic methods. Suitable bases include hydroxides of alkali metals (such as lithium, sodium or potassium). For example, the ester can be dissolved in a mixture of water and alcohol, such as ethanol. When handling sodium hydroxide or potassium hydroxide, an ester of its shades of obtaining sodium or potassium salt of carboxylic acid. Acidification with a strong acid, such as chlorine is standardna or sulfuric acid, gives a carboxylic acid of Formula 4F. Carboxylic acid can be distinguished by methods known in the art, including crystallization, extraction and distillation.

The compounds of Formula 38b can be obtained, shown in figure 20.

where R3is a CF3and R13represents a C1-C4alkyl.

Handling hydrazine of Formula 41 ketone of Formula 42 in a solvent such as water, methanol or acetic acid, gives the hydrazone of Formula 43. The person skilled in the art should be understood that it may be necessary to catalyze this reaction an optional acid, and may also be necessary to raise the temperature depending on the picture of the molecular substitution of the hydrazone of Formula 43. The interaction of the hydrazone of Formula 43 with the compound of the Formula 44 in a suitable organic solvent, such as (but without limitation) dichloromethane or tetrahydrofuran, in the presence of an acid acceptor, such as triethylamine, gives the compound of Formula 38. The reaction is usually carried out at a temperature ranging from about 0 to 100aboutC. the Hydrazines of the Formula 98 can be obtained by standard methods, such as contacting the halide compounds of Formula 23 (Scheme 15) with hydrazine.

Pyrazolylborate acid Form is s 4g, where R10represents Cl or Br, can be obtained by the method presented in Scheme 21.

where R13is1-C4alkyl.

Oxidation of compounds of Formula 45, optionally in the presence of acid to obtain the compounds of Formula 46 and then converting the functional group of ester carboxylic acid in the carboxylic acid gives compound of Formula 4g. The oxidizing agent may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, monopersulfate potassium (e.g., Oxone®) or potassium permanganate. For complete conversion, you must use at least one equivalent of oxidizing agent based on the compound of Formula 45, preferably from one to two equivalents. This oxidation is typically carried out in the presence of a solvent. The solvent may be a simple ether, such as tetrahydrofuran, p-dioxane, etc., complex organic ester, such as ethyl acetate, dimethylcarbonate and the like, or a polar organic solvent, such as N,N-dimethylformamide, acetonitrile, etc. Acids suitable for use on stage oxidation, include inorganic acids such as sulfuric acid, phosphoric acid, etc. and organic acids such as acetic acid, be sauna acid, etc. When using acid and should be used in amounts greater than 0.1 equivalent based on the compound of Formula 45. For complete conversion you can use from one to five equivalents of acid. The preferred oxidizing agent is potassium persulfate, and the oxidation is carried out in the presence of sulfuric acid. The reaction can be performed by mixing the compounds of Formula 45 in the desired solvent and, if it is used, acid. Then you can add the usual amount of oxidant. The reaction temperature usually ranges from about 0aboutWith up to the boiling point of the solvent, in order to achieve a reasonable reaction time to bring it to completion, preferably it is less than 8 hours. The desired product, compound of Formula 46, can be identified by methods known in the art, including crystallization, extraction and distillation. Methods suitable for the conversion of ester of Formula 46 in the carboxylic acid of Formula 4g, have been described for Scheme 19.

The compounds of Formula 45 can be obtained from corresponding compounds of Formula 47, as shown in figure 22.

where R13is1-C4alkyl.

Treatment of compounds of Formula 47 halogenation agent, usually in the presence of a solvent, gives sootvetstvuyushchee compound of Formula 45. Halogenation agents that can be used include oxychloride phosphorus, trihalogen phosphorus, pentachloride phosphorus, thionyl chloride, dialoginterface, dialoginterface, oxalicacid and phosgene. Preferred are oxychloride phosphorus and pentavalent phosphorus. For complete conversion, you must use at least 0.33 equivalent oxychloride phosphorus in the calculation of the compound of Formula 47, preferably from about 0.33 to about 1.2 equivalents. For complete conversion, you must use at least 0.20 equivalent pentachloride phosphorus in the calculation of the compound of Formula 47, preferably from about 0.20 to about 1.0 equivalents. For this reaction, the preferred are the compounds of Formula 47, where R13is1-C4alkyl. Typical solvents for this halogenation include halogenated alkanes such as dichloromethane, chloroform, dichlorobutane and the like, aromatic solvents such as benzene, xylene, dichlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane, diethyl ether and the like, polar aprotic solvents, such as acetonitrile, N,N-dimethylformamide, etc. is Optional, can be added an organic base, such as triethylamine, pyridine, N,N-dimethylene the n etc. The addition of a catalyst, such as N,N-dimethylformamide, is also optional. Preferred is a method in which the solvent is acetonitrile, and the base is missing. Typically, requires no Foundation, no catalyst, when the solvent used acetonitrile. The preferred method is carried out by mixing the compounds of Formula 47 in acetonitrile. Then add the halogenation agent for a suitable period of time, and the mixture is then incubated at the desired temperature until completion of the reaction. The reaction temperature is typically in the range of 20aboutC to the boiling point of acetonitrile, and the reaction time is typically less than 2 hours. Then the reaction mass is neutralized inorganic base, such as sodium bicarbonate, sodium hydroxide and the like, or an organic base, such as sodium acetate. The desired product, compound of Formula 45, can be identified by methods known in the art, including crystallization, extraction and distillation.

Alternatively, the compounds of Formula 45, where R10represents Br or Cl, can be obtained by treatment of the corresponding compounds of Formula 45, where R10is another halogen (such as Cl to obtain the compounds of Formula 45, where R10represents a bromine) or sulfone the ing group, such as p-toluensulfonate, hydrogen bromide or hydrogen chloride, respectively. When using this method, halogen or sulphonate substituent R10the initial compounds of Formula 45 is substituted by bromine or chlorine from hydrogen bromide or hydrogen chloride, respectively. The reaction is carried out in a suitable solvent, such as dibromomethane, dichloromethane or acetonitrile. The reaction can be performed at atmospheric pressure, or about, or at a pressure above atmospheric in the high-pressure apparatus. When R10in the initial compound of Formula 45 is a halogen, such as Cl, the reaction is preferably carried out in such a way that the halogen compound formed in the reaction, can be removed by bubbling or other suitable means. The reaction can be performed at a temperature in the range from 0 to 100aboutWith the most convenient temperature is about room temperature (for example, from about 10 to about 40aboutC) and most preferably in the range from 20 to 30aboutC. the Addition of the catalyst on the basis of a Lewis acid (such as tribromide aluminum, to obtain the compounds of Formula 45, where R10represents Br) promotes the reaction. The product of Formula 45 emit methods known in the art, including ex is raccio, distillation and crystallization.

The initial compounds of Formula 45, where R10represents Br or Cl, can be obtained from corresponding compounds of Formula 47, as described above. The initial compounds of Formula 45, where R10represents a sulphonate group, can also be obtained from corresponding compounds of Formula 47 standard methods such as treatment with sulphonylchloride (for example, p-toluensulfonate) and a base such as tertiary amine (e.g. triethylamine), in a suitable solvent such as dichloromethane.

Pyrazolylborate acid of the Formula 4h, where R10is a co2CF3you can get way presented in figure 23. In this way, instead of halogenation, as shown in figure 22, the compound of Formula 47 are oxidized to compounds of Formula 48. The reaction conditions for such oxidation described above for converting compounds of Formula 45 in the compound of Formula 46, as shown in Scheme 21.

Then the compound of Formula 48 alkylate with the formation of the compounds of Formula 50 by contact with an alkylation agent CF3CH2Lg (49) in the presence of a base. In the alkylation agent (49) Lg represents deleted in the reaction of nucleophilic substitution group such as halogen (such as Br, I), OS(O)2CH3(methanesulfonate), OS() 2CF3, OS(O)2Ph-p-CH3(p-toluensulfonate) and the like; it is advantageous to use methanesulfonate. The reaction is carried out in the presence of at least one equivalent of base. Suitable bases include inorganic bases, such as carbonates or hydroxides of alkali metals (such as lithium, sodium or potassium), and organic bases such as triethylamine, diisopropylethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene. Usually the reaction is carried out in a solvent, which may include alcohols such as methanol and ethanol, halogenated alkanes, such as dichloromethane, aromatic solvents such as benzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide and the like, Alcohols and polar aprotic solvents are preferred for use with inorganic bases. Potassium carbonate as base and acetonitrile as solvent are preferred. The reaction is usually carried out at a temperature in the range from 0 to 150aboutWith, most typically at a temperature of from about room temperature up to about 100aboutC. the Product of Formula 50 allocate more traditional methods, such as extraction. An ester of Formula 50 and then converted into the carboxylic acid of the Formula 4h method is mi, described above for converting compounds of Formula 40 in the compound of Formula 4f in figure 19.

where R8is1-C4alkyl and Lg represents a group to delete.

The compounds of Formula 47 can be obtained from compounds of Formula 41 (Scheme 20), as shown in Scheme 24.

where R13is1-C4alkyl.

In this way provide the contacting of the hydrazine of Formula 41 with the compound of the Formula 51 (you can use an ester of fumaric acid or an ester of maleic acid, or their mixture) in the presence of base and solvent. The base typically is a salt of an alkali metal such as sodium methoxide, potassium methoxide, ethoxide sodium, atoxic potassium tert-piperonyl potassium tert-piperonyl lithium, etc. you Must use more than 0.5 equivalent of base per connection Formula 51, preferably from 0.9 to 1.3 equivalents. You need to use more than 1.0 equivalent of the compound of Formula 108, preferably, from 1.0 to 1.3 equivalents. You can use proton polar and polar aprotic organic solvents (e.g. alcohols, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, dimethylsulfoxide and the like, the Preferred solvents are alcohols, is such as methanol and ethanol. Particularly preferably, the alcohol was the same from which to obtain an ester of fumaric or maleic acid and alkoxide basis. The reaction is typically carried out by mixing the compounds of Formula 108 and base in a solvent. The mixture can be heated or cooled to the desired temperature, and the compound of Formula 98 add for some period of time. Typically, the reaction temperature is in the range from 0aboutC to the boiling point of the used solvent. The reaction may be carried out at a pressure above atmospheric, in order to increase the boiling point of the solvent. Generally preferred is a temperature in the range from about 30 to about 90aboutC. While adding should be as short as this allows the heat transfer. Typical time added is from 1 min to 2 hours. The optimum reaction temperature and time add, vary with the nature of the compounds of Formula 98 and Formula 51. After the addition was finished the reaction mixture can be maintained for some time at the reaction temperature. Depending on the reaction temperature, the aging time can be from 0 to 2 hours. Typical aging time ranges from 10 to 60 minutes Then the reaction mass is acidified by the addition of organic acids such as acetic key is lots and the like, or inorganic acid, such as hydrochloric acid, sulfuric acid, etc. depending on the reaction conditions and methods of isolation, functional group-CO2R13in the compound of Formula 47 can be hydrolyzed to CO2N; for example, the presence of water in the reaction mixture can promote hydrolysis. If a carboxylic acid (-CO2N), it can be converted back in-CO2R13where R13represents a C1-C4alkyl, using methods of esterification, well known from the prior art. The desired product, compound of Formula 47 can be distinguished by methods known in the art, including crystallization, extraction and distillation.

The synthesis of representative peratrovich acids of the Formula 4i presented in figure 25. The interaction of complex keeeper of dimethylaminopyridine Formula 53 with substituted hydrazines of the Formula 30 gives the pyrazoles of Formula 54. Preferred substituents R5(C) include alkyl or halogenated, especially preferred is 2,2,2-triptorelin. Esters of Formula 54 is converted into an acid of Formula 4i standard method of hydrolysis.

Synthesis peratrovich acids of the Formula 4j belonging to the preferred group J-6, where R5represents amestoy 2-pyridyloxy group, attached in position 5 of the pyrazole nucleus rings presented in figure 26. This synthesis is carried out in accordance with the General method of synthesis presented in figure 27.

The synthesis of representative peratrovich acids of the Formula 4k, as well as alternative synthesis of compounds of Formula 4i presented in figure 27. The interaction of complex keeeper of dimethylaminopyridine Formula 53 with hydrazine gives the pyrazole of Formula 59. The interaction of the pyrazole of Formula 59 with an alkylation agent of the Formula 60 (R5(C)-Lg, where Lg represents a removable group, such as halogen (such as Br, I), OS(O)2CH3(methanesulfonate), OS(O)2CF3, OS(O)2Ph-p-CH3(p-toluensulfonate) and the like), gives a mixture of pyrazoles of Formula 61 and 62. The mixture of isomers of pyrazole easily share chromatographic methods and converted into the corresponding acid. Preferred substituents R5(C) include alkyl and halogenoalkane group.

Of particular note is the synthesis pyridinedimethanol acids of the Formula 4m related to the equation J-7, in which R5represents a substituted 2-pyridinyl and is associated with position 3 pyrazol ring, and an alternative synthesis of compounds of Formula 4j presented in figure 28. This method is carried out in accordance with the tvii with the General method of synthesis, presented in figure 27.

General method of synthesis perlovich acids of the Formula 4n presented in figure 29. Treatment of compounds of Formula 67 2,5-dimethoxytetrahydrofuran (68) gives the pyrrole of Formula 69. Formirovanie of pyrrole of Formula 69 with the formation of the aldehyde of Formula 70 can be performed using standard conditions formirovaniya Vilsmeier-Haack, such as N,N-dimethylformamide (DMF) and phosphorus oxychloride. Halogenoalkane the compounds of Formula 70 N-halogencontaining (NXS), such as N-chlorosuccinimide or N-bromosuccinimide, mainly occurs in position 4 of the pyrrole ring. Oxidation of halogenated aldehyde gives pyrrolone acid of the Formula 4n. The oxidation can be accomplished using a variety of standard oxidation conditions.

Synthesis of some piridincarbonova acids of the Formula o associated with the formula J-8, in which R5represents 2-pyridinyl, and is connected to the nitrogen atom of the pyrrole ring, presented in figure 30. The compound of Formula 72, 3-chloro-2-aminopyridine, is a known compound (see J.Heterocycl.Chem. 1987, 24(5), 1313-16). A convenient method for obtaining compounds of Formula 72 from 2-aminopyridine of Formula 71 includes the introduction of protective groups, ortho-metallation, chlorination and subsequent removal of the protection. Remained the Noah synthesis is carried out in accordance with the General method of synthesis, presented in figure 29.

Synthesis perlovich acids of the Formula 4P presented in figure 31. Cycloaddition of allene of the Formula 78 and phenylsulfonylacetate Formula 77 (.Pavri, N.P.; Trudell, M.L. J.Org.Chem. 1997, 62, 2649-2651) gives pyrrolin Formula 79. Processing of pyrroline Formula 79 tetrabutylammonium (TBAF) gives the pyrrole of the Formula 80. The interaction of a pyrrole of the Formula 80 with the alkylation agent R5(d)-Lg (where Lg represents a removable group that is defined above), followed by hydrolysis gives pyrrolone acid of the Formula 4P.

Synthesis perlovich acids of the Formula 4q, which are related to Formula J-9, where R5represents phenyl or 2-pyridyl and attached in position 2 of the pyrrole ring, presented in figure 32. The synthesis is carried out in accordance with the General method presented in figure 31.

Synthesis perlovich acids of the Formula 4r presented in figure 33. Interaction α,βunsaturated complex ester of the Formula 85 with p-tolylsulfochloride (TosMIC) gives the pyrrole of Formula 86. Guidelines for this synthesis, see Xu, Z. Et al., J.Org.Chem., 1988, 63, 5031-5041. The interaction of the pyrrole of Formula 86 with the alkylation agent R5(d)-Lg (where Lg represents a removable group that is defined above) with subsequent hydrolysis of the AET pyrrolone acid of the Formula 4r.

Synthesis perlovich acids of the Formula 4s, which are related to Formula J-6, where R5represents a substituted phenyl or substituted 2-pyridinoline ring presented in figure 34. The synthesis is carried out in accordance with the General method presented in figure 33.

You must understand that some reagents and reaction conditions described above for preparing compounds of Formula I may be incompatible with certain functional groups present in the intermediate compounds. In these cases, the inclusion in the procedure of synthesis stages of the introduction of protective groups/removal of the protective groups or interconversion of functional groups can be useful for obtaining the desired products. The use and choice of protective groups must be obvious to the expert in the field of chemical synthesis (see, for example, Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 2nded.; Wiley: New York, 1991). The person skilled in the art should understand that in some cases, after the introduction of a specific reagent, as indicated on any particular scheme, in order to bring the synthesis of compounds of Formula I to completion, it may be necessary to implement additional routine stages of synthesis, not described in detail. The specialist should be clear, cradle obtain the compounds of Formula I may need to implement a combination of stages, illustrated in the above schemes, in a different order than shown specific sequence of stages.

Also a specialist in this area should be clear that the described herein the compounds of Formula I and intermediate compounds can be subjected to various reactions, such as reactions with electrophiles, nucleophiles, radical, ORGANOMETALLIC compounds, reactions of oxidation and reduction, to add substituents or modify existing substituents.

Without further experimentation, the person skilled in the art can apply the present invention in its broadest scope, using the above description. Therefore, the examples below should be considered as merely illustrative and in no way limiting the present disclosure. Percentages are based on weight, except for mixtures of solvents for chromatography or if stated otherwise. Parts and percentages given for mixtures of solvents for chromatography are based on volume, unless otherwise indicated. Spectra1H-NMR are given in ppm, the area below the spectrum tetramethylsilane; means singlet, d means doublet, t means triplet, kV means Quartet, m means multiplet, DD means doublet of doublets, dt means doublet of triplets, IRS means broad singlet and shirt means a broad doublet.

EXAMPLE 1

Obtaining N-[2-methyl-6-[[(1-methylethyl)amino]sulfonyl] phenyl]-4-(triptoreline)benzamide

Stage a: 3-methyl-N-(1-methylethyl)-2-nitrobenzenesulfonamide

To a solution of Isopropylamine (13 ml, 155 mmol) in 60 ml of dichloromethane at 0°C was added dropwise a solution of 5.3 g of 3-methyl-2-nitrobenzenesulfonamide (obtained in accordance with the method Courtin, A. Helv. Chim. Acta, 1976, 59, 379-387) in 60 ml dichloromethane. The reaction mixture was stirred for 2 hours at room temperature. Added water and the layers were separated. The organic layer was dried (sodium sulfate), and volatile components were removed using a rotary evaporator. The residue was purified liquid medium pressure chromatography (MPLC)using as eluent 20-40% ethyl acetate in hexane, to obtain 4.3 g specified in the title compound as a yellow solid.

1H NMR (CDC13) δ of 1.12 (d, 6H), 2,39 (s, 1H), of 3.56 (m, 1H)and 4.65 (userd, 1H), 7,54 (m, 2H), to $ 7.91 (DD, 1H).

Stage B: Obtaining 2-amino-3-methyl-N-(1-methylethyl)benzosulfimide

To a mixture of 4.13 g of the substance from the Stage A and 0.25 g of 10% palladium on coal was added 150 ml of ethanol. The reaction mixture was stirred in the atmosphere belonoha hydrogen within three days. The mixture was filtered through celite and the solvent was removed using a rotary evaporator to obtain the 3.65 g specified in the title compound as brown is about oil.

1H NMR (CDC13) δ of 1.03 (d, 6H), of 2.21 (s, 1H), 3,60 (m, 1H), 4,57 (userd, 1H), 4,86 (users, 2H), 6.73 x (DD, 1H), 7,24 (d, 1H), to 7.64 (d, 1H).

Stage C: Obtaining N-[2-methyl-6-[[(1-methylethyl)amino]sulfonyl]phenyl]-4-(triptoreline)benzamide

To 0,30 g (1.4 mmol) of the material from step B in 5 ml of chloroform was added, and 0.28 ml (3.5 mmol) of pyridine and 0.27 ml (1.7 mmol) of 4-(triptoreline)of benzoyl chloride. The reaction mixture was stirred over night at room temperature and then was heated at the boil under reflux for 5 hours. After cooling to room temperature the reaction mixture is washed with 1N HCl, dried (sodium sulfate) and filtered. Volatile components were removed using a rotary evaporator. The residue was purified using MPLC (5-25% ethyl acetate in hexane as eluent) to obtain 0.10 g specified in the title compounds, the compounds according to the invention, in the form of a white solid, melting at 104-107°C.

1H NMR (CDC13) δ 0,99 (d, 6H), a 2.36 (s, 1H), 3,32 (m, 1H), 4,07 (userd, 1H), 7,35 (m, 3H), 7,56 (d, 1H), 7,89 (d, 1H), with 8.05 (d, 2H), 8,78 (users, 1H).

EXAMPLE 2

Getting 2-[[[1-(3-Chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]sulfonyl]-amino]-3-methyl-N-(1-methylethyl)benzamide

Stage a: 3-chloro-2-[3-(trifluoromethyl)-lH-pyrazole-1-yl]pyridine

To a mixture of 2,3-dichloropyridine (99,0 g, 0.67 mol) and 3-cryptomaterial (83 g, 0.61 mol) in anhydrous is N,N-dimethylformamide (300 ml) was added potassium carbonate (166,0 g, 1.2 mol) and the reaction was then heated to 110-125°C for 48 hours. The reaction mixture was cooled to 100°C and filtered through diatomaceous auxiliary filtering material Celite® for solids removal. N,N-Dimethylformamide and excess dichloropyridine was removed by distillation at atmospheric pressure. Distillation (distillation) of the product under reduced pressure (so Kip. 139-141°C, 7 mm) gave the desired intermediate compound in the form of a clear yellow oil (to 113.4 g).

1H NMR (CDC13) δ is 6.78 (s, 1H), was 7.36 (t, 1H), to 7.93 (d, 1H), 8,15 (s, 1H), 8,45 (d, 1H).

Stage B: Obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-sulfonate lithium

To a solution of Isopropylamine (2.5 ml, 30 mmol) in 25 ml of tetrahydrofuran at a temperature of -78°C was added dropwise and 7.1 ml (18 mmol) of a 2.5m solution of n-utility in hexane. The resulting solution was added via cannula to a solution of 4.0 g of 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine (i.e. specified in the title compound from step A) in 50 ml of tetrahydrofuran at a temperature of -78°C. the Reaction mixture became orange. After 15 min was added 20 ml of tetrahydrofuran. Within 5 min after the solution was barbotirovany sulfur dioxide. The orange color disappeared. After 15 min the reaction mixture was filtered and the solvent removed from the filtrate using a rotary evaporator. The residue was rubbing the simple ether with obtaining a 4.53 g specified in the connection header in the form of not-quite-white solid.

1H NMR (D2O) δ was 7.08 (s, 1H), 7,72 (DD, 1H), 8,24 (DD, 1H), 8,55 (DD, 1H).

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

To 100 ml of pH 6 buffer (obtained by dissolving 1.2 g (10 mmol) of sodium dihydrophosphate in 100 ml of water and the addition of 11.2 ml of a 1N solution of sodium hydroxide) was added to 3.52 g (11.1 mmol) specified in the header Stage B substances. The resulting solution was cooled in an ice bath was added 75 ml of ethyl acetate and 1.48 g (11.1 mmol) of N-chlorosuccinimide. After 30 min, the layers were separated. The organic layer was dried (sodium sulfate) and the solvent was removed using a rotary evaporator. To the residue was added carbon tetrachloride and the solids were removed by filtration. The solvent of the filtrate was removed using a rotary evaporator to obtain 2,84 g specified in the connection header in the form of oil of amber.

1H NMR (CDC13) δ was 7.45 (s, 1H), 7,58 (DD, 1H), 8,01 (DD, 1H), 8,58 (DD, 1H).

Study D: Obtain 3-methyl-N-(1-methylethyl)-2-nitrobenzamide

A solution of 3-methyl-2-nitrobenzoic acid (2.00 g, 11.0 mmol) and triethylamine (1.22 g, 12.1 mmol) in 25 ml dichloromethane was cooled to 10°C. was Carefully added ethylchloride, which led to the formation of a solid precipitate. After stirring the mixture for 30 min, was added Isopropylamine (0,94 g, 16.0 mmol) and obtained a homogeneous solution. Reaction the second mixture was stirred for another hour, was poured into water and was extracted with ethyl acetate. The organic extracts were washed with water, dried over magnesium sulfate and evaporated under reduced pressure to get a 1.96 g of the desired intermediate as a white solid, melting at 126-128°C.

1H NMR (CDC13) δ to 1.24 (d, 6H), of 2.38 (s, 3H), 4,22 (m, 1H), 5,80 (users, 1H), and 7.4 (m, 3H).

Stage E: Obtaining 2-amino-3-methyl-N-(1-methylethylbenzene)

2-Nitrobenzamide with Stage D (1.70 g, 7.6 mmol) was first made over 5% palladium on carbon in 40 ml ethanol at a pressure of 345 kPa (50 psi). After cessation of hydrogen absorption, the reaction mixture was filtered through Celite filter material® and Celite® washed with ether. The filtrate is evaporated under reduced pressure to get 1,41 g specified in the connection header in the form of a solid, melting at 149-151°C.

1H NMR (CDC13) δ 1,24 (DD, 6H), of 2.16 (s, 3H), 4,25 (m, 1H), 5,54 (users, 2H), 5,85 (users, 1H), 6,59 (t, 1H), 7,13 (d, 1H), 7,17 (d, 1H).

Stage F: Obtain 2-[[[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]sulfonyl]amino]-3-methyl-N-(1-methylethyl]benzamide

To 2,84 g (10.2 mmol) of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-sulfonic acid (i.e. specified in the header Phase C connection) in 70 ml of dichloromethane was added to 1.96 g (10.2 mmol) of 2-amino-3-methyl-N-(1-methylethyl)benzamide (teamcasanova in the heading Stage E connection) of 1.78 ml (10.2 mmol) of diisopropylethylamine and about 5 mg of 4-(dimethylamino)pyridine. The reaction mixture was stirred for 9 h, then washed with water and dried (sodium sulfate). The solvent was removed using a rotary evaporator. The residue was purified using MPLC (20-40% ethyl acetate in hexane as eluent) to give 0.50 g specified in the connection header in the form of a foamy white solid, melting at 69-72°C.

1H NMR (CDC13) δ 0,1,12 (d, 6H), 2,32 (s, 1H), 3,85 (m, 1H), 5,96 (userd, 1H), 7,07 (s, 1H), 7,35 (m, 3H), 7,39 (DD, 1H), 7,89 (DD, 1H), to 8.20 (DD, 1H), 9,26 (s, 1H).

EXAMPLE 3

Obtain 3-Bromo-1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-(3-methyl-1-oxobutyl)phenyl]-1H-pyrazole-5-carboxamide

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

To a solution of N,N-dimethylsulphamoyl (44,0 g, 0,251 mol) in anhydrous tetrahydrofuran (500 ml) at a temperature of -78°C was added dropwise a solution of n-utility (2.5 M in hexane, 105,5 ml, 0,264 mol), while maintaining the temperature below -60°C. during the addition formed a dense solid. Upon completion of addition the reaction mixture was stirred for 15 min, then was added dropwise a solution of 1,2-dibromotetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150 ml), while maintaining the temperature below -70°C. the Reaction mixture became transparent, buying orange color, and the stirring was continued for 15 more settled in. Bath with a temperature of -78°C was removed and the reaction extinguished with water (600 ml). The reaction mixture was extracted with dichloromethane (4x), and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was then purified using chromatography on silica gel, using as eluent dichloromethane-hexane (50:50), with specified title compound as a clear colorless oil (57,04 g).

1H NMR (CDC13) δ of 3.07 (d, 6H), 6,44 (m, 1H), 7.62mm (m, 1H).

Stage B: 3-bromopyrazole

To triperoxonane acid (70 ml) was slowly added 3-bromo-N,N-dimethyl-1H-pyrazole-1-sulfonamide (i.e. product bromopyrazole Stage A) (57,04 g). The reaction mixture was stirred at room temperature for 30 min and then concentrated under reduced pressure. The residue was absorbed hexane, and the insoluble solids were filtered off and the hexane evaporated to obtain the crude product as oil. The crude product was then purified using chromatography on silica gel, using as eluent ethyl acetate/dichloromethane (10:90) to obtain the oil. The resulting oil was absorbed dichloromethane, neutralized with an aqueous solution of sodium bicarbonate, extracted with dichloromethane (3x), dried over magnesium sulfate and concentrated to obtain specified in the title compounds as white is solid substances (25.9 g), TPL 61-64°C.

1H NMR (CDC13) δ 6,37 (d, 1H), to 7.59 (d, 1H), 12,4 (users, 1H).

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

To a mixture of 2,3-dichloropyridine (27.4 g, 185 mmol) and 3-bromopyrazole (i.e. the product of Stage (B) (25.4 g, 176 mmol) in anhydrous N,N-dimethylformamide (88 ml) was added potassium carbonate (48.6 g, 352 mmol) and the reaction mixture was heated to 125°C for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 ml). There was a formation of sludge. Water the mixture of precipitated solids were stirred for 1.5 hours, filtered and washed with water (2x100 ml). The solid filter cake was consumed dichloromethane and washed successively with water, 1N-hydrochloric acid, saturated aqueous sodium bicarbonate and saturated saline solution. The organic extracts were then dried over magnesium sulfate and concentrated to obtain and 39.9 g of solid hot pink color. The crude solid is suspended in hexane and was intensively stirred for 1 hour. The solid was filtered, washed with hexane and dried to obtain specified in the connection header as not quite white powder (30,4 g), the purity of which, by definition, by NMR, was >94. This substance is used at the Stage D without additionally the cleanup.

1H NMR (CDC13) δ of 6.52 (s, 1H), 7,30 (DD, 1H), 7,92 (d, 1H), with 8.05 (s, 1H), 8,43 (d, 1H).

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

To a solution of 2-(3-bromo-1H-pyrazole-1-yl)-3-chloropyridine (i.e. product pyrazole Stage C) (30,4 g, 118 mmol) in anhydrous tetrahydrofuran (250 ml) at a temperature of -76°C was added dropwise a solution of diisopropylamide lithium (118 mmol) in tetrahydrofuran with such a rate as to maintain the temperature below -71°C. the Reaction mixture was stirred for 15 minutes at a temperature of -76°C, and then through it was barbotirovany carbon dioxide for 10 minutes, causing heating of the mixture to -57°C. the Reaction mixture was heated to -20°C and extinguished with water. The reaction mixture was concentrated and then absorbed water (1 l) and a simple ether (500 ml), then was added 1N aqueous sodium hydroxide solution (20 ml). Water extracts were washed with ether and acidified with hydrochloric acid. The precipitated solid was filtered, washed with water and dried to obtain specified in the title compound as a tan solid (27.7 g). (The product of another cycle, using the same procedure melted at a temperature 200-201°C)

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

Stage E: Obtain 3-Bromo-1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-(3-methyl-1-OK is butil)phenyl]-1H-pyrazole-5-carboxamide

To a solution of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. product pyrazole Stage D) (500 mg, of 1.65 mmol) in dichloromethane (10 ml) was added 1 drop of N,N-dimethylformamide. Added oxalicacid (of 0.43 ml, 5 mmol) and the mixture was stirred at 23°C for 1 hour. The solvent was removed under reduced pressure and the residue was diluted with acetonitrile (20 ml) and the solvent was again removed under reduced pressure. The residue was dissolved in tetrahydrofuran (10 ml) and treated with 1-(2-amino-3-were)-3-methyl-1-butanone obtained in accordance with Chem. Pharm. Bull, 2000, 48, 1-15 (330 mg, 1.6 mmol) and then triethylamine (0.45 ml, 3.2 mmol). The mixture was heated at a temperature of 60°C for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 ml) and water (50 ml). The organic layer was washed with water (2×30 ml) and 1N solution of hydrochloric acid (2×30 ml). The separated organic layer was dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel, using as eluent ethyl acetate/hexane (3:7). The appropriate fractions were combined to give, after removal of the solvents indicated in the title compounds, the compounds according to the invention (210 mg)as a yellow terduga substance, melting at 119-120°C.

1H NMR (CDCl3) δ 0,97 (d, 6N), 2,21 (who, 3H), 2,84 (d, 2H), 7,06 (s, 1H), 7,21 (m, 1H), and 7.4 (m,2H), a 7.62 (d, 1H), 7,81 (d, 1H), 8,42 (d, 1H), 10,6 (user., 1H).

EXAMPLE 4

Getting methylamide 2-amino-3-methylbenzoic acid

A mixture of 8-methyl-1H-benzo[d][1,3]oxazin-2,4-dione (18 g, 0.1 mmol) and acetic acid (1.2 g, 0.02 mmol) in ethyl acetate (200 ml) was heated to 35°and was added dropwise a 40% aqueous solution of methylamine (9.0 g, 0.12 mmol) for 15 minutes at a temperature of 35-37°C. After all matilainen was added, the mixture was additionally stirred for 2.5 hours at 36°C. Then was added water (20 ml), the layers were separated and the organic layer was washed with water, dried over magnesium sulfate and evaporated to obtain 15,45 g (92%) specified in the connection header.

1H NMR (CDCl3) δ 2.14 (s, 3H), 2.94 (d, 3H, J=5 Hz), 5.37 (users, 2H), 6.21 (users, 1H), 6.56 (t, J=7.5 Hz, 1H), 7.10 (DD, J=7.5 Hz, 7.5 Hz, 1H), 7.18 (DD, J=7.5 Hz, 7.5 Hz, 1H).

EXAMPLE 5

Getting methylamide 2-amino-5-chloro-3-methylbenzoic acid

The mixture methylamide 2-amino-3-methylbenzoic acid (product of example 4) (16.6 g, 100 mmol) and N,N-dimethylformamide (15,0) was cooled to 10°and was slowly added concentrated aqueous solution of hydrochloric acid (70 g, 700 mmol). Then the mixture was heated to 30°and was added dropwise a 30% aqueous hydrogen peroxide solution (18.5 g, 160 mmol) for 15 minutes at a temperature of 30-35°C. the mixture is Then stirred at about 35° C for 3 hours, cooled to 10°and added water (200 ml). Was added sodium sulfate (7,56 g, 60 mmol) and brought the pH to 2.2, slowly adding 50% aqueous sodium hydroxide solution (38,1 g). After stirring at 10°C for 15 minutes, the mixture was filtered, the solids washed with water (2×50 ml) and dried in a vacuum oven to obtain 14,61 g of compound (yield 72,7%) specified in the title compound as a pink solid.

EXAMPLE 6

Getting methylamide 2-amino-5-bromo-3-methylbenzoic acid

The mixture methylamide 2-amino-3-methylbenzoic acid (product of example 4) (14 g, 85 mmol), acetic acid (50 ml) and water (50 ml) was cooled to 12°and added a concentrated aqueous solution of Hydrobromic acid (28.5 g, 0.34 mol) for 10 minutes at this temperature. Then was added 30% aqueous hydrogen peroxide solution (9 g, 0.08 mol) over 15 minutes at 10-11°leaving the mixture to warm slowly to room temperature and was stirred for 2.5 hours. Then added more concentrated aqueous solution of Hydrobromic acid (2.9 g), the mixture is stirred over night at room temperature. To the mixture was added water (50 ml) and sodium bisulfate (1.5 g) and then brought the pH to 5-6 by adding 50% aqueous solution of hydoxide sodium (about 15 ml). The mixture was filtered, the solids washed in the Oh and dried in vacuum to obtain 19.5 g (94%) specified in the connection header.

1H NMR (CDCl3) δ 2.14 (s, 3H), 2.95 (d, J=5 Hz, 3H), 5.55 (users, 2H), 6.01 (users, 1H), 7.21 (m, 1H), 7.30 (d, J=2 Hz, 1H).

Using the above techniques together with the known from the prior art methods, it is possible to obtain the following compounds of Tables 1 to 12. In the Tables use the following abbreviations: i means ISO, Me means methyl, Pr means propyl, i-Pr means isopropyl, Ph means phenyl, OMe means methoxy, SMe means methylthio, CN means cyano, and NO2means nitro.

The INDEX TABLE G
ConnectionR3R4AR4bTPL °
G1 (Example 4)CH3CH3N120-122
G2 (Example 5)CH3CH3Cl141-143
G3 (Example 6}CH3CH3Br*
* Cm. the index table H1H NMR
TABLE INDEXES N
Connection # 1H NMR data (CDCl3if not initially identified)
G3δ and 2.14 (s, 3H), 2.95 points (d, J=5 Hz, 3H), 5,55 (ush. s, 2H), 6,01 (ush. s, 1H), 7,21 (m, 1H), 7,30 (d, J=2 Hz, 1H)

Composition/applicability

Compounds of the present invention, as a rule, can be used in the form of formulations or compositions with acceptable agricultural carrier, including at least one of a liquid diluent, a solid diluent or a surfactant. The ingredients of the composition or compositions are chosen so that they match the physical properties of the active ingredient, the method of application and the features of the environment such as soil type, moisture and temperature. Useful formulations include liquids, such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions), etc. which may not necessarily be thickened to a gel. Useful formulations also include solid formulations such as on the texts powders, granules, fine particles, tablets, films, etc. that may be water-dispersible ("wet") or water-soluble. The active ingredient may be (micro)encapsulated and can then be formed suspension or solid composition; alternatively, the entire composition of the active ingredient can be encapsulated (or "coated"). Encapsulating controlled or slow release of the active ingredient. Spray compositions can be diluted in a suitable medium and can be used when the volume of spray from one to several liters per hectare. Highly concentrated compositions are mainly used as intermediate compounds for further formulation.

The compositions typically contain an effective amount of the active ingredient, diluent and surfactant, approximately following the limits of that together make up 100 percent by weight.

Mass percentage
The active ingredientthinnerSurfactant
Water-dispersible and water-soluble granules, tablets and powders5-900-941-15
Suspensions, emulsions, solutions (including emulsifiable concentrates)5-5040-950-15
Dusty1-2570-990-5
Granules and fine particles0,01-995-99,990-15
Highly concentrated compositions90-990-100-2

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

Surfactants include, for example, polyethoxysiloxane alcohols, polyethoxysiloxane alkyl phenols, esters polyethoxylated fatty acids sorbitan, diallylmalonate, alkyl sulphates, alkylbenzenesulfonate, organosilicon compounds, N,N-dialkylamide, ligninsulfonate, condensates of naphthalenesulfonate and formal is degidi, polycarboxylate and block copolymers of polyoxyethylene/polyoxypropylene. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silicon dioxide, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and sodium bicarbonate and sodium sulfate. Liquid diluents include, for example, water, N,N-dimethylformamide, dimethylsulfoxide, N-alkylpyridine, ethylene glycol, polypropyleneglycol, paraffins, alkyl benzenes, alkylnaphthalene, olive, castor, linseed, Tung, sesame, corn, peanut oil, cotton, soybean, rapeseed and coconut oil, esters of fatty acids, ketones, such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols, such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.

Solutions, including emulsifiable concentrates, can be obtained simply by mixing the ingredients. Dusty and powders can be obtained by mixing and grinding, for example, a hammer mill or grinding using liquid. Suspensions are usually obtained by wet grinding; see, for example, U.S. 3,060,084. Granules and fine particles can be obtained by spraying the active substance onto preformed granular carriers or by agglomeration. Cm. Broning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer''s Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and PCT publication WO 91/13546. Fine particles can be obtained, as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be obtained, as described in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be obtained, as described in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Film can be obtained, as described in GB 2,095,558 and U.S. 3,299,566.

Additional information regarding known methods of obtaining compositions, see T. S. Woods, "The Formulator''s Toolbox - Produuct Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. Cm. also U.S. 3,235,361, No. 6, line 16 to No. 7, line 19 and Examples 10-41; U.S. 3,309,192, No. 5, line 43 No. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132,138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, No. 3, line 66 No. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

The following Examples all percentages are based on weight, and all of the compositions obtained in the usual way. The numbers of compounds are compounds in the Reference Table A.

An example of A

Wettable powder

Connection 165,0%
polietilenglikolya ether dodecylphenol 2,0%
Ligninsulfonate sodium4,0%
Silicoaluminate sodium6,0%
Montmorillonite (calcinated)23,0%

Example B

Granules

Connection 110,0%
Attapulgite granules (low-volatile substance, of 0.71/0.30 mm; U.S.S. sieve No. 25-50)90,0%

Example C

Extrudable granules

Connection 125,0%
Anhydrous sodium sulfate10,0%
The crude lignosulfonate calcium5,0%
alkylnaphthalene sodium1,0%
Calcium/magnesium bentonite59,0%

Example D

Emulsifiable concentrate

Connection 120,0%
The mixture is soluble in the oil sulfonates and polyoxyethylene ethers10,0%
isophorone70,0%

Example F

Granules

2,5%
Connection 10,5%
Cellulose
Lactose4,0%
Corn flour93,0%

Compounds of the present invention differ favorable nature of metabolism and/or residual content in the soil and are active to fight with a number of agricultural and non-agricultural invertebrate pests. (In the context of this description, "combating invertebrate pests" means the inhibition of the development of invertebrate pests (including death)that leads to a significant reduction eating or other harm or damage caused by pests; such expressions are defined in a similar way). Used in this description, the term "invertebrate pests" includes arthropods, gastropods and nematodes, which from an economic point of view are problematic pests. The term "arthropods" includes insects, bugs, spiders, Scorpions, centipedes, of, woodlice and Simpel. The term "gastropods" includes snails, slugs and other Stylommatophora. The term "nematode" includes all types of worms, such as roundworms, heartworms and herbivorous nematodes (Nematoda), trematodes (Tematoda), Acanthocephala and tapeworms (Cestoda). The specialist in this area should be clear that not all connections are equal to the effect of the ate against all kinds of pests. Compounds of the present invention show activity against relevant from an economic point of view agricultural and non-agricultural pest. The term "agriculture" refers to the production of field crops, such as used for the production of food and fiber, and includes the cultivation of cereal crops (e.g. wheat, oats, barley, rye, rice, maize), soybeans, vegetable crops (e.g. lettuce, cabbage, tomatoes, beans), potatoes, sweet potatoes, grapes, cotton and fruit trees (e.g. Apple, stone fruit and citrus). The term "non-agricultural" is applicable in respect of other horticultural crops (e.g., forest plants, greenhouse plants, plants, planted to protect other crops, or ornamental plants that do not grow in the field), health and animal health, residential and commercial premises, household and food storage, or in respect of the pests of these crops. In order to combat a wide range of pests and for reasons of economic importance, protection from damage or destruction caused by invertebrate pests) such crops as cotton, corn, soy, rice, vegetables, potatoes, sweet potatoes, grapes and fruit trees, by which ontrol invertebrate pests is a preferred embodiment of the present invention. Agricultural or non-agricultural pests include such pests like caterpillars detachment of butterflies (Lepidoptera)such as "marching worms, podgryzayuschie scoop, the geometrid moths and caterpillars of the family Noctuidae (e.g., autumn "marching worms (Spodoptera fugiperda J. E. Smith), beet "marching worms (Spodoptera exigua Hübner), scoop Upsilon (Agrotis ipsilon Hufnagel), scoop or (Trichoplusia ni Hübner), bollworm tobacco (Heliothis virescens Fabricius)); grinders, czechanski, caterpillars, building spider socket, coneworms, mermaidy and skeletonema leaves pests of the family Pyralidae (e.g., corn borer (Ostrinia nubilalis Hübner), caterpillar pests of citrus (Amyelois transitella Walker), Ognevka (Crambus caliginosellus Clemens), the beet webworm (Herpetogramma licarsisalis Walker)); leafrollers, leafrollers pockety, pests of seeds and fruit worms in the family Tortricidae (e.g., Codling moth (Cydia pomonella Linnaeus), grape moth (Endopiza viteana Clemens), tortrix Oriental peach (Grapholita molesta Busck)); and many other relevant from an economic point of view Lepidoptera (e.g., the cabbage moth (Plutella xylostella Linnaeus), pink boxed worm of cotton (Pectinophora gossypiella Saunders), Gypsy moth (Lymantria dispar Linnaeus)); nymphs and adults of troop Blattodea including cockroaches families Blattellidae and Blattidae (e.g., black cockroach (Blatta orientalis Linnaeus), Asian cockroach (Blatella asahinai Mizukubo), red cockroach (Blattella germanicaLinnaeus), cockroach brown-striped (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunnea Burmeister), Madeira cockroach (Lencophaea maderae Fabricius)); eating the foliage, larvae and adults of the order of Coleoptera including weevils families Anthribidae, Bruchidae, and Curculionidae (e.g., the weevil cotton (Anthonomus grandis Boheman), rice weevil water (Lissorhoptrus oryzophilus Kuschel), granary weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oryzae Linnaeus)); excavation of a flea, beetle blaska potato, leaf, Colorado potato beetles and moths-minelayers number of the family Chrysomelidae (e.g., Colorado potato beetle (Leptinotarsa decemlineata Say), blocka Donousa (Diabrotica virgifera virgifera LeConte)); Khrushchev and other beetles of the family Scaribaeidae (for example, garden chafer Japanese (Popillia japonica Newman) and garden chafer European (Rhizotrogus majalis Razoumowsky)); beetles koreeda family Dermestidae; wireworms family Elateridae; bark beetles of the family Scolytidae and larval small flour of the family Tenebrionidae. In addition, agricultural and non-agricultural pests include: adult and larvae squad Dermaptera, including earwig family Forficulidae (e.g., haverty European (Forficula auriculana Linnaeus), haverty black (Chelisoches morio Fabricius)); adults and nymphs of units Hemiptera and Homoptera such as, bugs-kanaky family Miridae, cicadas family Cicadidae, cycatki (e.g., Empoasca spp.) the family Cicadellidae, Delphi is IDA families Fulgoroidae and Delphacidae, the humpback of the family Membracidae, listblock family Psyllidae, whiteflies family Aleyrodidae, aphids of the family Aphididae, phylloxera family Phylloxeridae, mealybugs of the family Pseudococcidae, scales of the families Coccidae, Diaspididae and Margarodidae, bugs-lace-family Tingidae, bugs-defenders of the family Pentatomidae, white-winged bugs (e.g., Blissus spp.) and other bugs of the family Lygaeidae, pennisi family Cercopidae, squash bugs of the family Coreidae, and krasnolipe family Pyrrhocoridae. This list also includes adult and larvae squad Acari (mites)such as spider mites and red mites in the family Tetranychidae (e.g., the fishing season Klasik (Panonychus ulmi Koch), clasic spider bimaculated (Tetranychus urticae Koch), clasic McDaniel (Tetranychus mcdanieli McGregor)), flat mites in the family Tenuipalpidae (e.g., clasic flat citrus (Brevipalpus lewisi McGregor)), Klasik of Lehengas and clasic Gallic family Eriophyidae and other devouring the foliage of ticks and mites injurious to the health of humans and animals, i.e. dust mites in the family Epidermoptidae, zeleznici family Demodicidae, grain mites in the family Glycyphagidae, ticks squad Ixodidae (e.g., Ixodes tick (Ixodes scapularis Say), Australian prilichnyi tick (Ixodes holocyclus Neumann), Ixodes tick variable (Dermacentor variabilis Say), mite odnozvezdochny (Amblyomma americanum Linnaeus) and mite horse and Sarcoptes scabiei families Psoroptidae, Pyemotidae, and Sarcoptidae; adult and immature specimens of Orthoptera order, including prygun the key and crickets (e.g., locusts (e.g., Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American locust (e.g., Schistocerca americana Drury), desert locust (Schistocerca gregaria Forskal), locust campaign (Locusta migratoria Linnaeus), house cricket (Acheta domesticus Linnaeus), mole crickets (Gryllotalpa spp.)); adults and immature individuals detachment Diptera, including moth-minelayers number, small two-winged insects, fruit flies (Tephritidae), Swedish fly (e.g., Oscinella frit Linnaeus), soil maggots of flies, flies bedroom (e.g., Musca domestica Linnaeus), small house flies (e.g., Fannia canicularis Linnaeus, F.femoralis Stein), gigalo autumn (e.g., Stomoxys calcitrans Linnaeus), face flies, gigalo cow small, patelnie flies (e.g., Chrysomya spp., Phormia spp.), and other mehoopany winged insect pests, horse flies (e.g., Tabanus spp.), botflies (e.g., Gastrophilus spp., Oestrus spp.), larvae bullish Hypoderma (e.g., Hypoderma spp.), deer botflies (e.g., Chrysops spp.), runty sheep (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), midges (e.g., Prosimulium spp., Simulium spp.), biting midges, blackflies, clarity and other Nematocera; adults and immature individuals detachment Thysanoptera, including thrips (Thrips tabaci Lindeman) and other devouring the foliage thrips; insect pests of the order Hymenoptera including ants (e.g., red ant-bark beetles (Camponotus ferrugineus Fabricius), the ant-tree-borer, Pennsylvania (Camponotus pennsylvanicus De Geer), Pharaoh ant (Monomorium pharaonis innaeus), Tasmania (Wasmannia auropunctata Roger), ant Richter (Solenopsis geminata Fabricius), ant Richter (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), paratrechina (Paratrechina longicornis Latreille), ant sod (Tetramorium caespitum Linnaeus), ant field (Lashis alienus Forster), the ant Tapinoma sessile (Tapinoma sessile Say)), bees (including bees-the carpenters), large wasps, these wasps and burrowing wasps; insect pests of the detachment Isoptera, including termite yellow-footed (Reticulitermes flavipes Kollar), termite Reticulitermes hesperus (Reticulitermes hesperus Banks), the termite Coptotermes formosanus (Coptotermes formosanus Shiraki), West Indian wood termite (Incisitermes immigrans Snyder) and other termites of importance from an economic point of view; insect pests of the detachment Thysanura such as Chechulina (Lepisma saccharina Linnaeus) and Chechulina home (Thermobia domestica Packard); insect pests of the detachment Mallophaga and including the head louse (Pediculus humanus capitis De Geer), louse (Pediculus humanus humanus Linnaeus), pakhoed (Menacanthus stramineus Nitszch), flashed dog (Trichodectes canis De Geer), pogoed chicken petrobrazi (Goniocotes gallinae De Geer), sheep louse (Bovicola ovis Schrank), the louse of cattle Korotkova blood-sucking (Haematopinus eurysternus Nitzsch), the louse of cattle golgonooza blood-sucking (Linognathus vituli Linnaeus) and other sucking and chewing lice are parasites that attack man and animals; insect pests of the detachment Siphonoptera including flea Eastern rat (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), nl the dog ha (Ctenocephalides canis Curtis), flea chicken (Ceratophyllus gallinae Schrank), flea suction (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas infecting mammals and birds. Other covered arthropods pests include spider squad Araneae, such as the spider, the brown recluse (Loxosceles reclusa Gertsch &Mulaik) and spider-weaver black (Latrodectus mactans Fabricius), and Gubanova squad Scutigeromorpha, such as Flycatcher common (Scutigera coleoptrata Linnaeus). Compounds of the present invention also show activity against members of the class Nematoda, Cestoda, Trematoda, and Acanthocephala, including relevant from an economic point of view of the members of the groups Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida, such as, but not limited to, relevant from an economic point of view of agricultural pests (i.e. nematodes tuberous crops of the genus Meloidogyne, infecting nematodes of the genus Pratylenchus, nematodes roots of the stump of the genus Trichodorus, etc) and pests harmful to the health of humans and animals (i.e. everything of importance from the economic point of view, flukes, tapeworms and roundworms, such as Strongylus vulgaris in horses, Toxocara canis in dogs, At contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus from ruminant and so on).

Compounds of the present invention show particularly high activity against pests of Lepidoptera (e.g., labama argillacea Hü bner (caterpillar shovels cotton American), Archips argyrospila Walker (fruit-tree tortrix), A. rosana Linnaeus (tortrix European) and other Archips species, Chilo suppressalis Walker (Ognevka rice), Cnaphalocrosis medinalis Guenee (rice moth), Crambus caliginosellus Clemens (Ognevka corn root), Crambus teterrellus Zincken (Ognevka Crambus teterrellus), Cydia pomonella Linnaeus (Codling moth), Earias insulana Boisduval (cotton bollworm prickly), Earias vittella Fabricius (cotton bollworm spotted), Helicoverpa armigera Hübner (cotton bollworm American), Helicoverpa zea Boddie (boxed worm), Heliothis virescens Fabricius (scoop tobacco), Herpetogramma licarsisalis Walker (the beet webworm), Lobesia botrana Denis & Schiffermüller (moth vine), Pectinophora gossypiella Saunders (pink boxed cotton worm), Phyllocnistis citrella Stainton (mol-miner number and citrus), Pieris brassicae Linnaeus (cabbage white butterfly), Pieris rapae Linnaeus (butterfly-replica), Plutella xylostella Linnaeus (cabbage moth), Spodoptera exigua Hübner (beet "marching worms"), Spodoptera litura Fabricius (podgryzayuschie scoop tobacco, caterpillar growing grapes crops), Spodoptera frugiperda J. E. Smith (the fall "marching worms"), Trichoplusia ni Hübner (scoop) and Tuta absoluta Meyrick (mol-miner number and tomato)). Compounds of the present invention also have a commercially significant activity against members of the order Homoptera including: Acyrthisiphon pisum Harris (pea aphid), Aphis craccivora Koch (black aphids alfalfa), Aphis fabae Scopoli (black aphids Bobo the traveler, Aphis gossypii Glover (cotton aphid), Aphis pomi De Geer (aphid Codling), Aphis spiraecola Patch (aphid Tamagawa), Aulacorthum solani Kaltenbach (aphid vonkova), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (wheat aphid), Dysaphis plantaginea Paaserini (aphid pink), Eriosoma lanigerum Hausmann (aphid blood leaf), Hyalopterus pruni Geoffroy (aphids, mealy plum), Lipaphis erysimi Kaltenbach (aphid lookupentry), Metopolophium dirrhodum Walker (aphids cereal crops), Macrosipum euphorbiae Thomas (potato aphid sheet), Myzus persicae Sulzer (peach aphid), Nasonovia ribisnigri Mosley (aphid latalowa), Pemphigus spp. (root aphids and gallarraga aphid), Rhopalosiphum maidis Fitch (aphid corn leaf), Rhopalosiphum padi Linnaeus (cherry aphid-Osawa), Schizaphis graminum Rondani (cereal aphid common), Sitobion avenae Fabricius (cereal aphid), Therioaphis maculata Buckton (aphid spotted alfalfa), Toxoptera aurantii Boyer de Fonscolombe (black aphids citrus) and Toxoptera citricida Kirkaldy (aphids brown citrus); Adelges spp. (heresy); Phylloxera devastatrix Pergande (phylloxera Hickory); Bemisia tabaci Gennadius (tobacco whitefly, sweet potato whitefly), Bemisia argentifolii Bellows &Perring (whiteflies), Dialeurodes citri Ashmead (citrus whitefly) and Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (Cicada potato), Laodelphax triatellus Fallen (small brown delphacidae), Macrolestes quadrilineatus Forbes (Cicada star), Nephotettix cinticeps Uhler (Cicada green), Nephotettix nigropictus Stel (Cicada rice), Nilaparvata lugens Stel (Cicada brown), Peregrinus maidis Ashmead (Cicada corn), ogatella furcifera Horvath (Cicada short-tailed), Sogatodes orizicola Muir (delphacidae rice), Typhlocyba pomaria McAtee (Cicada Apple), Erythroneoura spp. (Cicada grape); Magicidada septendecim Linnaeus (periodical Cicada); Icerya purchasi Maskell (mealybug Australian grooved), Quadraspidiotus perniciosus Comstock (bugs, San Jose); Planococcus citri Risso (mealybug grape powdery); Pseudococcus spp. (another group of scale insects); Cacopsylla pyricola Foerster (medenica pear), Trioza diospyri Ashmead (listblock Jurmala). Compounds according to the invention also show activity against members of the order Hemiptera including: Acrosternum hilare Say (bug-green activist), Anasa tristis De Geer (bug-rombout), Blissus lencopterus lencopterus Say (white-winged bug), Corythuca gossypii Fabricius (cotton bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich-Schäffer (Krasnogo cotton), Euchistus servus Say (bug-activist brown), Euchistus variolarius Palisot de Beauvois (bug-activist adenopathy), Graptosthetus spp. (some kinds of bugs seeds), Leptoglossus corculus Say (bug-crevic pine), Lygus lineolaris Palisot de Beauvois (klopik meadow), Nezara viridula Linnaeus (bug cotton gardening), Oebalus pugnax Fabricius (rice bug), Oncopeltus fasciatus Dallas (bug Euphorbiaceae large), Pseudatomoscelis seriatus Reuter (cotton flea). Other insect orders, kontroliruemykh compounds of the present invention, include Thysanoptera (e.g., Frankliniella occidentalis Pergande (thrips Western flower), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (trips soy) and Thrips tabaci Lindeman (thrips); and the order Coleoptera (e.g the measures Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and nematodes of the genera Agriotes, Athous or Limonius).

Compounds of the present invention can also be mixed with one or more other biologically active compounds or agents including insecticides, fungicides, nematicides, bactericides, acaricides, growth regulators, such as growth promoters roots, chemical sterilizers, polychemical, repellents, attractants, pheromones, stimulants nutrition, other biologically active compounds or entomopathogenic bacteria, virus or fungi, obtaining multi-component pesticide with an even wider range of applications in agriculture. Thus, the compositions of the present invention may also include a biologically effective amount of at least one additional biologically active compound or substance. Examples of such biologically active compounds or substances, with which the compounds of the present invention can be formulated in a single composition, include: insecticides such as abamectin, Arafat, acetamiprid, avermectin, azadirachtin, azinphos-methyl, bifenthrin, benvenist, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyfluthrin, beta-zyflo is Rin, cigalotrin, lambda cigalotrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, giovanola, emamectin, endosulfan, esfenvalerate, ethiprole, fanatical, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flucythrinate, Tau-fluvalinate, flufenoxuron, fonofos, halogenated, hexaflumuron, Imidacloprid, indoxacarb, isofenphos, lufenuron, Malathion, metaldehyde, metamidophos, methidathion, methomyl, methoprene, Methoxychlor, monocrotophos, methoxyfenozide, nithiazine, novaluron, oxamyl, parathion, parathion-methyl, permethrin, Fort, fosalan, phosmet, Poseidon, pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxifen, rotenon, spinosad, sulprofos, tebufenozide, teflubenzuron, tefluthrin, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosulfat-sodium, tralomethrin, trichlorfon and triflumuron; fungicides, such as acibenzolar, AZOXYSTROBIN, benomyl, blasticidin-S, Bordeaux mixture (trehosnovnoy copper sulphate), bromuconazole, napropamide, captafol, Captan, carbendazim, chloroneb, CHLOROTHALONIL, copper oxychloride, copper salt, cyflufenamid, having cymoxanil, tsyprokonazolu, cyprodinil, (S)is 3.5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281), diclocil (S-2900), declomycin, dicloran, difenoconazol, (S) - for 3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imidazol-4-one (RP 47213), dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, Dodin, edifenphos, epoxiconazol, famoxadone, fenamidone, fenarimol, fenbuconazole, paneramic (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, fluazinam, fludyoksonil flamethower (RPA 403397), fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, parallaxis, parameter (S-82658), hexaconazole, ipconazole, iprobenfos, iprodion, isoprothiolane, kasugamycin, kresoxim-methyl, MANCOZEB, MANEB, mefenoxam, mepronil, metalaxyl, metconazole, metamine-strobin/phenominalrose (SSF-126), myclobutanil, neo-atzin (metanational iron), oxadixyl, penconazole, pencycuron, provenzal, prochloraz, propamocarb, propiconazol, pirivenas, pyraclostrobin, Pyrimethanil, pyroxylin, jenoxifen, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazol, teriflunomide, thiophanate-methyl, thiram, tadini, triadimefon, triadimenol, tricyclazole, Trifloxystrobin, triticonazole, validamycin and vinclozolin; nematicides, such as aldicarb, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides, such as amitraz, chinomethionat, Chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological substances, such as the Bacillus thuingiensis, including subspecies aizawai and kurstaki Delta endotoxin of Bacillus thuringiensis, baculovirus, and entomopathogenic bacteria, viruses and fungi. Compounds of the present invention and compositions of these compounds can be used to genetically transformed plants for the expression of proteins toxic to invertebrate pests (such as Bacillus thuringiensis toxin). The effect of exogenously applied compounds for controlling invertebrate pests of the present invention may be synergistic with excessively toxin proteins.

General information about agricultural protectant can be found in The Pesticide Manual, 12th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2000.

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

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

In some cases, for dealing with pests particularly preferred can be combined with other compounds or substances for control of invertebrate pests, with the same spectrum of control but a different mode of action. Thus, the compositions of the present invention may also include a biologically effective amount of at least one additional compound or substance for controlling invertebrate pests, with the same spectrum of control but a different mode of action. Contacting a genetically modified plants for the expression of protecting plant compounds (e.g., protein), or where there is a plant with a biologically effective amount of the compounds according to the invention may also provide a broader range of protection of plants and can be advantageous for the organization of pest control.

Combating invertebrate pests has agricultural and non-agricultural purpose, and it is carried out by applying one or more compounds of the present invention, in an effective amount, to the habitat of pests, including agricultural and neslisah the agricultural site of infection, to the area to be protected, or directly on the pests that are struggling. Thus, the present invention also includes a method of combating invertebrate pests for use in agricultural and/or non-agricultural areas, including contacting bespozvonochnykh pest or its environment with a biologically effective amount of one or more compounds of the present invention, or a composition comprising at least one such compound, or composition comprising at least one such compound and an effective amount of at least one additional biologically active compound or substance. Examples of suitable compositions comprising the compound of the present invention and an effective amount of at least one additional biologically active compounds or substances, include the composition of the granules, where additional biologically active compound or substance is present on the same pellet as the connection of the present invention, or other granules, separate from those containing the compound of the present invention.

Preferred method of contact is by spraying. Alternatively, the composition in pellet form comprising compound present is ademu the invention, can be applied to the foliage of plants or to the soil. Compounds of the present invention can also be easily delivered by absorption of the plant when contacting the plant with a composition comprising the compound of the present invention, which are used for impregnation of the soil in the form of liquid compositions, granular composition, applied to soil for podtachivaniya protective trees or dive grafts. The compounds are also effective for topical application of a composition comprising the compound of the present invention, on the site of infection. Other methods of contact include the application of a compound or composition according to the present invention by direct or residual spraying, atomizing, in the form of a gel, by covering the seeds, microencapsulation, systemic absorption, lures, labels, boles, smoke, fumigants, aerosols, Farrukh Dustov and many other ways. The compounds of the present invention can also be impregnated materials for the manufacture of devices of the control of invertebrate pests (e.g. mosquito nets).

Compounds of the present invention can be included in bait consumed by invertebrate pests, or in devices such as traps, etc. Granules or baits, comprising 0.01 to 5% of the active ingredient, 0.05 to 10% of the substance(s), keep the surrounding moisture, and 40-99% vegetable flour, are effective against soil dwelling insects at very low application rates, in particular, the dose of the active ingredient, which is lethal in the absorption and not by direct contact.

Compounds of the present invention can be applied in their pure form, but most often using a composition comprising one or more compounds with suitable carriers, diluents or surface-active substances and, possibly, in combination with food, depending on end use. The preferred method of application involves spraying water dispersion or purified oil solution of the compounds. Combination with spray oils, concentrates, spray oils, sticky substances for spraying, adjuvants, other solvents and synergists, such as piperonylbutoxide, often increases the efficiency of the connection.

The rate of application required for effective control (i.e. the "biologically effective amount"depends on such factors as type is subject to control bespozvonochnykh pest life cycle of the pest, stage of development, its size, location, season, culture or animal host, a way of eating, a way of mating, ambient moisture, temperature, etc. In normal conditions nor the s of about from 0.01 to 2 kg of active ingredient per hectare are sufficient for pest control in agricultural ecosystems, but may be sufficient for such a small amount as of 0.0001 kg/ha, or can take up to 8 kg/ha For non-agricultural applications, the consumption rate is in the range from about 1.0 to about 50 mg/sq m, but may be sufficient for such a small amount as 0.1 mg/m, or you may have up to 150 mg/sqm person skilled in the art can easily determine the biologically effective amount necessary for the desired level of control of invertebrate pests.

The following TESTS demonstrate the effectiveness of the control for the compounds of the present invention with respect to specific pests. "Effective control" means the inhibition of the development of invertebrate pests (including death), resulting in significantly reduced power. However, the pest control provided by the compounds of the present invention, is not limited to these species. Description of the connections, see the Reference tables a and B. In the Reference tables use the following abbreviations: "Me" means methyl, "i" means ISO, "Pr" means propyl and i-Pr means isopropyl. The abbreviation "Etc." means "Example" and the number of the sample that was received on the connection.

The informational table And

ConnectionR4R3JTPLabout
1IUi-Pr4-Cl-phenyl208-210
2(PR)IUi-Pr1-(3-Cl-2-pyridinyl)-3-CF3-5-pyrazole69-72
The reference table In the

ConnectionR4R3JTPLabout
B1IUi-Pr4-CF3-phenyl139-142
B2(App.1)IUi-Pr4-OCF3-phenyl104-107
B3IUi-Pr1-(3-Cl-2-pyridinyl)-3-CF 3-5-pyrazolyl69-73
Reference chart

ConnectionR4R3JTPLabout
C1IUi-Bu1-(3-Cl-2-pyridinyl)-3-CF3-5-pyrazolyl138-140
C2(PR)IUi-Bu1-(3-Cl-2-pyridinyl)-3-Br-5-pyrazolyl119-120
C3MeEt1-(3-Cl-2-pyridinyl)-3-Br-5-pyrazolyl185-186
C4MeMe1-(3-Cl-2-pyridinyl)-3-Br-5-pyrazolyl133-135
C5MeMe1-(3-Cl-2-pyridinyl)-3-CF3-5-pyrazolyl113-114
C6 Mei-Pr1-(3-Cl-2-pyridinyl)-3-Br-5-pyrazolyl102-104
C7Mei-Pr1-(3-Cl-2-pyridinyl)-3-CF3-5-pyrazolyl124-125
Reference chart D

ConnectionR4R3JTPL °
D1MeEt1-(3-Cl-2-pyridinyl)-3-Br-5-pyrazolyl152-154
D2MeMe1-(3-Cl-2-pyridinyl)-3-Br-5-pyrazolyl181-182
The informational TABLE E

ConnectionR3(R4)nR10R9TPL °

E1-CH2NO22-CH3, 4ClCF3Cl*
E2-CH2C(=O)och2CH32-CH3, 4ClCF3Cl*
EZ-CH(CN)C(=O)och2CH32-CH3, 4ClCF3Cl*
E4-CH(C(=O)CH3)C(=O)och2CH32-CH3, 4ClCF3Cl*
E5-CH2SO2CH32-CH3, 4ClCF3Cl*
E6-CH2SO2CH(CH3)22-CH3, 4CNClCl*
E7-CH2SO2CH(CH3)22-CH3, 4ClCF3Cl*
E8-CH2C(=O)och2CH32-CH3, 4CNBrCl*
E9i-Bu2-CH3, 4ClBrCl165-166
E10i-Pr2-CH3, 4ClClCl168-169
TABLE INDEXES F
Conn. No.Data1H NMR (CDCl solution3if not stated otherwise)a
E1(DMSO-d6) δ 10,70 (s, 1H), to 8.57 (d, 1H), they were 8.22 (d, 1H), 7,82 (d, 1H), 7,75-of 7.60 (m, 3H), from 6.22 (s, 2H), and 2.27 (s, 3H)
E2δ 10,14 (s, 1H), 8,48 (d, 1H), 7,89 (d, 1H), 7,58 (d, 1H), 7,42-7,38 (m, 2H), 7,26 (s, 1H), 4,22 (kV, 2H), 3.96 points (s, 2H), 2,31 (s, 3H), of 1.24 (t, 3H)
E3(Acetone-d6) δ 9,78 (width, <1H), 8,55 (d, 1H), 8,12 (d, 1H), 7,60 (DD, 1H), EUR 7.57 (s, 1H), 7,5 to 7.4 (m, 2H), 4,30-to 4.15 (m, 2H), 3,62 (wide s, 1H), 2,30 (s, 3H), 1,29 (distorted t, 3H).
E4(partial range) δ 7,78 (width d, 1H), 7,58 (width d,

1H), 2,48 (s, 3H), from 0.88 (t, 3H).
E5δ 9,42 (s, 1H), 8,43 (d, 1H), of 7.90 (d, 1H), 7,60 (apparent s, 1H), 7,42-7,38 (m, 2H), 7,28 (s, 1H), 4,50 (s, 2H), 3,11 (s, 3H, 2, 21 (s, 3H).
E6δ 9,87 (s, 1H), 8,42 (d, 1H), 8,07 (s, 1H), 7,87 (d, 1H), of 7.70 (s, 1H), 7,39 (DD, 1H), 6,98 (1N), to 4.52 (s, N), 3,43 (septet, 1H), and 2.27 (s, 3H), 1,45 (d, 6N).
E7δ 9,58 (wide s, 1H), 8,48 (d, 1H), to $ 7.91 (d, 1H), 7,76 (d, 1H), 7,43-7,40 (m, 2H), 7,26 (s, 1H), 4,49 (s, 2H), 3,48 (m, 1H), of 2.23 (s, 3H), of 1.46 (d, 3H), 1, 44 (d, 3H).
E8(mixture of amide rotamers) δ to 11.52 and of 11.29 (s, 1H total), 8,42 (distorted d, 1H), 7,92 and 7.69 (s, 1H total), 7,86 (distorted d, 1H), 7,58 and 7,46 (s, 1H), 7,42 and 7.36 (m, 1H), 7,06 and of 6.99 (s, 1H total), a 4.3-was 4.02 (m, 2H), is 3.08 (AB kV, 2H), 2.26 and and of 2.21 (s, 3H), 1,28-of 1.18 (m, 3H).
aData1H-NMR are given in ppm in the lower field from tetramethylsilane. The peaks of the signals are indicated as follows: with means singlet, d means doublet, t means triplet, kV means Quartet, m means multiplet, DD means doublet of doublets, dt means doublet of triplets, and Shir with means broad singlet.

BIOLOGICAL EXAMPLES of the INVENTION

TEST AND

For evaluating control of cabbage moth (Plutella xylostella) installation for testing consisted of a small open container containing within 12-14-day plant radish. It was pre-infected 10-15 svezhevyrosshimi larvae on the fragment forage for insects, using a sampler for sampling the "tube" from the layer dense food, containing many growing on it, larvae, and transfer tube containing larvae and diet to the test. If the Incas moved on to the test plant as drying tube feed.

The composition of the test compounds was obtained using a solution containing 10% acetone, 90% water and 300 ppm non-ionic surfactant X-77® Spreader Lo-Foam Formula, containing alkalinisation, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.), if not stated otherwise. Formulated in the composition of the compounds were applied in 1 ml of liquid through the spray nozzle SUJ2 housing 1/8 JJ (Sptaying Systems Co.), located at the top, at a height of 1.27 cm (0.5 inch) from each plant for testing. All the tested compounds in this experiment was sprayed at a concentration of 250 ppm (or lower) with three repetitions. After spraying formulated into the composition of the test compound at each installation for testing was left to dry for 1 hour, then top to put black mesh cover. Installation for testing was kept for 6 days in the chamber for cultivation at a temperature of 25°C and relative humidity of 70%. Then visually assessed the damage to plants caused by eating it.

Of the tested compounds the compounds listed below, provided excellent levels of plant protection (20% or less of the damage caused by eating plants): I*, B3*, C2**, C5* C6*, E1**, E3*, E5,**, E7*, e** E10**.

TEST

For evaluating control of autumn "marching worms (Spodoptera frugiperda) is set for trial consisted of a small open container, containing within 4-5-day plant corn. It was pre-infected 10-15 larvae day of age on the fragment of the diet of an insect using the sampler as described in Test A.

Test compounds were formulated in the composition was sprayed at a concentration of 250 ppm (or lower), as described for Test A. the Coating compositions were repeated three times. After spraying installation for testing was kept in the chamber for growing and then visually assessed the damage to the plants as described for Test A.

Of the tested compounds the compounds listed below, provided excellent levels of plant protection (20% or less of the damage caused by grazing plants): C2* C5* E5**.

TEST

For evaluating control of tobacco Cutworm (Heliothis virescens) installation for testing consisted of a small open container containing within 6-7-day plant cotton. It was pre-infected 8 2-day larvae on the fragment of the diet of an insect using the sampler as described in Test A.

Test compounds were formulated in the composition was sprayed at a concentration of 250 ppm (or lower), as described for Test A. the Coating compositions were repeated three times. After spraying installation for testing was kept in the chamber for growing is then visually assessed the damage to the plants, as described for Test A.

Of the tested compounds the compounds listed below, provided excellent levels of plant protection (20% or less of the damage caused by eating plants): C2* C6*.

*Experienced at 50 h/million

**Tested with a 10 h/million

1. Orthotamine arylamide formula I

where J is a phenyl ring or a pyrazol ring, where each ring is substituted by one or two substituents, independently selected from R5;

It represents-NR1C(=A) -, or-NR1SO2-;

L represents-C(=B)NR2-, -SO2NR2- or- (=) -;

A and b represent About;

R1represents N;

R2represents N;

R3represents a C1-C6alkyl, optionally substituted by one or more substituents independently selected from the group comprising CN, NO2With1-C4alkylsulfonyl and C2-C6alkoxycarbonyl;

each R4independently represents a C1-C6alkyl, halogen or CN;

each R5independently represents a C1-C6halogenated, halogen or C1-C4halogenoalkane; or

each R5independently represents p is reinel, optionally substituted by one Deputy, is independently selected from R9;

R9is a halogen; and

n has a value from 1 to 2;

provided that when a represents-NR1C(=A), then L is other than-C(=O)NR2-,

and its salts.

2. The compound according to claim 1, in which It represents-NR1C(=A).

3. The compound according to claim 1, in which L represents-C(=B)NR2-.

4. The compound according to claim 2 or 3, in which R3represents a C1-C6alkyl, optionally substituted by one or more substituents independently selected from the group including CN and C1-C2alkylsulfonyl;

one of the groups R4attached to the rest of the formula I or in position 2 or position 4 of the phenyl ring, and the specified R4represents a C1-C4alkyl, halogen or CN;

each R5independently represents a C1-C4halogenated, halogen or C1-C4halogenoalkane; or

each R5independently represents a pyridinyl optionally substituted by one Deputy, selected from R9; and

n has a value of 1 or 2.

5. The compound according to claim 4,

in which R3represents a C1-C4alkyl, optionally substituted by CN Il is S(O) 2CH3; and

one R5associated with J orthopaedie relatively K.

6. The compound according to claim 5, in which

one R4attached to the rest of the formula I in position 2 of the phenyl ring ortho relative to the K-J fragment, and selected from the group comprising C1-C3alkyl, and, optionally, the second R4attached in position 4 of the phenyl ring, a pair of relatively K-J fragment, and selected from the group comprising halogen.

7. The connection according to claim 6, in which J represents

J-5

R5represents a

V represents N;

each R10represents H, C1-C6halogenated or halogen; and

R9represents a halogen.

8. The connection according to claim 7,

in which R10is a CF3or halogen.

9. The connection of claim 8,

where J represents the J-5;

R9represents Cl; R10represents a halogen or CF3.

10. The compound according to claim 1, which is a

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

11. A method of combating insects comprising contacting insects or surround the her their environment with a biologically effective amount of a compound according to claim 1, or a suitable salt.

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

13. The compound of formula 2

where R3represents isopropyl or methyl;

R4arepresents methyl or Cl; and

R4brepresents H, Cl or Br,

provided that

(a) when R4arepresents methyl and R4brepresents hydrogen, then R3is not isopropyl;

(b) when R4brepresents N, then R4ais not Cl; and

(c) when R4aand R4brepresent Cl, then R3is not isopropyl or its salt.

14. The connection 13, in which R3represents methyl, R4arepresents methyl and R4brepresents hydrogen.

15. The connection 13, in which R3represents methyl, R4arepresents methyl and R4brepresents Cl.



 

Same patents:

FIELD: organic chemistry, pharmaceuticals.

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

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

15 cl, 3 tbl, 109 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

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

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

32 cl, 10 tbl, 129 ex

FIELD: organic chemistry, medicine, pharmacy.

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

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

EFFECT: valuable medicinal properties of compounds and agent.

10 cl, 1 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

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

EFFECT: valuable medicinal properties of compounds.

13 cl, 26 ex

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

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

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

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 5 tbl, 32 ex

FIELD: organic chemistry, medicine, pharmacy.

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

EFFECT: valuable medicinal properties of compounds and composition.

7 cl, 1 tbl, 66 ex

FIELD: organic chemistry, medicine, pharmacy.

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

EFFECT: valuable medicinal properties of agent.

6 cl, 32 ex

FIELD: organic chemistry, pharmacy.

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

and

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

EFFECT: valuable medicinal properties of compounds.

18 cl, 5 tbl, 16 ex

FIELD: organic chemistry, medicine, pharmacology, pharmacy.

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

,

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

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

99 cl, 1 tbl, 414 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

FIELD: pharmaceuticals, organic chemistry.

SUBSTANCE: invention relates to anthranilic acid amides of general formula I , wherein R1 represents or

R2 represents hydrogen or alkyl; R3 represents dialkoxyphenyl; R4, R5, R6, R7 represent hydrogen, halogen alkyl. Pharmaceutical composition based on compounds of formula I and uses thereof in pharmaceutical agent production. Abovementioned compounds are useful as antiarrhythmic biologically active agents in particular for prevention and prophylaxis of arrhythmias.

EFFECT: new agents for prevention and prophylaxis of arrhythmias.

13 cl, 152 ex

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to new compounds of formula

,

wherein A and B are independently CH or CR3; X is C=O or (CR4aR4b)m, (m = 1 or 2); Y is S(O)n-R2 (n = 1 or 2), S(O)n-NR2R2, or S(O)n-OR2; N1 and N2 are nitrogen atoms; Q and R1 are independently 1) optionally substituted C1-C10-alkyl; 2) optionally substituted aralkyl containing C6-C10-aryl, attached to C1-C10-alkyl; 3) optionally substituted aralkenyl containing C5-C10-aryl, attached to C1-C10-alkenyl; 4) optionally substituted C6-C10-aryl; 5) optionally substituted aryl, containing 5-10 ring atoms, selected from carbon and sulfur; each R2 and R3 are hydrogen; R4a, R4b, R5, and R6, are independently hydrogen; R2 and R3 are independently hydrogen or C1-C6-alkyl; as well as acid and base additive salts thereof. Also disclosed are method for production of claimed compounds, pharmaceutical composition inhibiting serine protease enzymes and therapeutic method based thereon.

EFFECT: new compounds and pharmaceutical composition for thrombosis preventing or abnormal thrombosis treatment.

11 cl, 7 tbl, 15 ex

The invention relates to the derivatives of aminophenylamino formula I

< / BR>
where R is phenyl, substituted C1-C6by alkyl; R1represents hydrogen; X represents -(CH2)3-Y, cyclopropyl or tetrahydro-2-oxo-3-furoyl; Y represents chlorine, bromine or hydroxy,

or their acid additive salts

The invention relates to new nitromethylene formula (I)

< / BR>
in which A represents C6-C10aryl, thienyl, benzothiazyl; X denotes halogen, cyano, C1-C7alkyl, trifluoromethyl, C2-C7alkoxy, or cryptometer; p is chosen from 0, 1, 2, 3, 4, or 5; Z represents a bond, -CO-NH-, SO2-NH-, a sulfur atom, sulfinyl group or a C2-C7alkenylamine radical; R1, R2, R3and E indicated in paragraph 1

New ketoenamine // 2190599
The invention relates to new ketoenamine formula (1), where R1means phenyl, naphthyl, hinely, pyridyl, chinadoll, Minoxidil, benzothiazyl, isoquinoline, tetrahydroisoquinoline or tetrahydroquinolin, which may be unsubstituted or substituted, R2means hydrogen or alkyl, R3means alkyl, which may carry phenyl ring, X is a bond, -(CH2)m-, -(CH2)m-O-(CH2)0-, -(CH2)n-S-(CH2)m-, -CH= CH-, -CO-CH=CH-, -(CH2)m-NHCO-(CH2)0-, -(CH2)m-CONH-(CH2)0-, -(CH2)m-NHSO2-(CH2)0-, -(CH2)m-SO2NH-(CH2)0-; R4means group OR6, NR7R8; n is a number from 0 to 2

New benzamidomethyl // 2189973
The invention relates to new derivatives of benzamidomethyl formula (I), where R1- phenyl, naphthalene, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, pyridine, hinzelin, cinoxacin, and aromatic and heteroaromatic ring can be substituted by the radicals R4; R2is hydrogen, chlorine, bromine, fluorine, alkyl, -NHCO-naphthyl, -NHSO2- C1-4-alkyl, -O-C1-4-alkyl, -CO-NH - C1-4-alkyl, NO2; R3is a hydrocarbon residue with 1 to 6 carbon atoms, which may carry cycloalkyl, indolenine, phenyl ring, or a residue group-SCH3-; R4- alkyl, -O-C1-4-alkyl, chlorine, fluorine, bromine, iodine, CF3, pyridine; X is a bond, - (CH2)m-, - (CH2)m-O-(CH2)0-, - (CH2)m-S-(CH2)o-, - (CH2)m-SO- (CH2)o-, - (CH2)m-SO2- (CH2)0-, -CH=CH-, -CC-, -CO-CH=CH-, -CH= CH-CO-, - (CH2)m-CO-(CH2)0-, - (CH2)m-NR5CO-(CH2)0-, (R5=H, C1-4-alkyl), - (CH2)m- CONR5-(CH2)0-, - (CH2)m-NHSO2-(CH2)0-, - (CH2)m-SO2NH-(CH2)0-, -N

The invention relates to alkyl substituted cyclic amines of the formula I, where X and Y are in position 5, 6 or 7, where (i) n = 1, X represents (CH2)mCONR4R5, (CH2)mNR4CONR5, (CH2)mNHSO2R3(where m = 0 or 1, except that when m = 0, then Y cannot be hydrogen and Y is hydrogen or or6; (ii) n = 0 or 1, then X and Y are in the 0-position relative to each other and together form a: a) -C(O)NR10C(O)-, b) -C(O)NR4(CH2)xNR10C(O)- (where x = 0 or 1); (C) -CH2NR10C(O)-; d) -(CH2)NR10C(O) -, (e) -CH2C(O)NR10, g) -N(R3)-C(O)-O-, j) -CH2N(R8)CH2-; (iii) n = 0, and Y represents OR9then X is (CH2)mCONR4R5, (CH2)mNHCOR3(where m = 0 or 1); R1and R2represent, independently, WITH1-C8-alkyl, R3is1-C8-alkyl, aryl; R4and R5represent, independently, H, C1-C8-alkyl, C1-C6-alkylaryl or aryl; R6is1-C8-alkyl, R8is1-C8-alkyl, SO2R4(provided that R4is not hydrogen); R10is H, C is phenyl, possibly replaced by stands, nitro, chlorine, fluorine, bromine, amino, CN, carboxamido, acetyl; or represents thiophenyl, isoxazolyl, imidazolyl

The invention relates to new derivatives of aryl - and heteroarylboronic General formula I, where R1denotes a substituted phenyl or pyridyl, R2denotes a substituted phenyl, R3denotes hydrogen, (lower)alkyl, cyano, carboxy, esterified carboxylate, phenyl, 1H-tetrazolyl or the group,- CONR5R6, R5denotes hydrogen or the radical R7, R6represents -(CH2)mR7or R5and R6together with the nitrogen atom to which they are attached, denote morpholino, 2,6-dimethylmorpholine, piperidino, 4-(lower)alkylpiperazine, 4-(lower)alkoxyimino, 4-(lower)alkoxycarbonylmethyl or 4 formylpiperazine,7denotes phenyl, substituted phenyl, pyridyl, 1H-tetrazolyl, (lower)alkyl, cyano(lower)alkyl, hydroxy(lower)alkyl, di(lower)alkylamino(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl or phenyl(lower)alkoxycarbonyl, Radenotes hydrogen or hydroxy, Rbrepresents hydrogen, Z represents hydroxy or the group-OR8or-OC(O)NR8, R8denotes pyridyl or pyrimidinyl, X represents nitrogen or CH, m is 0, 1 or 2, n is 0, 1 or 2, and

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to compounds of formula I ,

where R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30), and R(31) are disclosed in claims. Compound of present invention are particularly useful as new antiarrythmia bioactive substances, in particular for treatment and prophylaxis of atrial arrhythmia (e.g., atrial fibrillation or auricular flutter).

EFFECT: higher efficiency.

13 cl, 18 ex, 1 tbl

The invention relates to thiosulfonate formulas

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or

< / BR>
< / BR>
< / BR>
where R1represents a radical having a length greater than the saturated chain of four carbon atoms, and shorter than the saturated chain from eighteen carbon atoms, and in rotation around the axis passing through the position 1, associated with the SO2and position 4 6-membered ring or through position 1, associated with the SO2group and associated with the Deputy position 3 or 5 of the 5-membered ring, defines a three-dimensional volume, the largest size in which the width is approximately one phenyl ring up to three phenyl rings in a direction transverse to the axis of rotation; R2means hydrido,1-C6alkyl, phenyl-C1-C4alkyl, heteroaryl-C1-C4alkyl, C2-C4alkyl substituted amino; C2-C4alkyl, substituted monosubstituted amino or disubstituted amino, where-C6) alkyl, C5-C8cycloalkyl and C1-C6alkylsulphonyl, or where two of the substituent and the nitrogen to which they are attached, together form pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, and other pyrimidinyl
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