Pesticidal compositions

FIELD: chemistry.

SUBSTANCE: described are novel heteroaryl-N-aryl-carbamates of general formula , where: Ar1 is phenyl, probably substituted with C1-C6halogenalkyl or C1-C6halogenalkoxy; Het is triazolyl; Ar2 is phenyl; X1 represents O or S; X2 - O; R4 - H or C1-C6alkyl; n=0, 1 or 2; and R1, R2 and R3 are independently selected from H, CN, C1-C6alkyl, C1-C6halogenalkyl, C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkinyl, C(=O)O(C1-C6alkyl), phenyl and Het-1, where Het-1 is a 5-membered unsaturated heterocyclic ring, containing one heteroatom, selected from sulphur or hydrogen, or a 6-membered unsaturated heterocyclic ring, containing one nitrogen atom as a heteroatom, and Het-1 can be substituted with F, Cl, C1-C6alkyl, C1-C6halogenalkyl or C1-C6alkoxy, and a method of fighting pest insects Lepidoptera or Homoptera with the application of the said compounds as insecticides and acaricides.

EFFECT: increased efficiency.

5 cl, 2 tbl, 80 ex

 

The technical FIELD TO WHICH the INVENTION RELATES

This application claims the benefit of provisional application U.S. serial number 61/232142, filed August 7, 2009. The invention disclosed in this document relates to the field of pesticides and their use to control insect pests.

BACKGROUND of INVENTION

Insect pests cause millions of deaths worldwide. In addition, there are more than ten thousand species of insect pests that cause loss of agricultural production. These losses of agricultural products constitute each year billions of dollars. Termites violate the integrity of the (damage) of various structures, such as houses. The losses from those caused by termites losses are every year billions of dollars. As a casting notes, many insect pests that live in the stored food, eat and worsen stored food products. Such losses associated with the loss of stored food products are billions of dollars annually, but more importantly, deprive people of food.

There is an urgent need for new pesticides. Insects develop resistance to pesticides used at the present time. Hundred and insect species are resistant to one or to many pesticides. The development of resistance to some of the older pesticides, such as DDT, carbamates and organophosphorus compounds, is well known. But resistance has developed even to some of the newer pesticides. Thus, there is a need for new pesticides and, in particular, in pesticides, which have new mechanisms of action.

DEPUTIES (INCOMPLETE LIST)

Examples for substituents (except halogen substituents), are incomplete and should not be construed as limiting the invention disclosed in this document.

"Alkenyl" means acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, Deputy consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonanal and decanal.

"Alkenylacyl is alkenyl, optionally containing carbon-oxygen single bond, for example, alliancegroup, butenyloxy, pentyloxy, hexaniacinate, heptyloxy, octenylsuccinate, nonyloxy and decisionsupport.

"Alkoxygroup" means alkyl, optionally containing carbon-oxygen single bond, for example, a methoxy group, ethoxypropan, propoxylate, from which propoxylate, 1-butoxypropyl, 2-butoxypropyl, isobutoxy,tert-butoxypropyl, phenoxypropan, 2-methylbutoxy, 1,1-DIMETHYLPROPANE, hexachrome, epoxypropyl, actorship, nonassignable and deoxyribo.

"Alkyl" represents an acyclic, saturated, branched or unbranched, Deputy containing carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl, isobutyl,tert-butyl, pentyl, 2-methylbutyl, 1,1-dimethylpropyl, hexyl, heptyl, octyl, nonyl and decyl.

"Quinil" means acyclic, unsaturated (having at least one carbon-carbon triple bond, and any number of double bonds), branched or unbranched, Deputy containing carbon and hydrogen, for example, ethinyl, propargyl, butynyl, pentenyl, hexenyl, heptenyl, octenyl, nominal and decenyl.

"Alkyloxy" is a quinil, optionally containing carbon-oxygen single bond, for example, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy and designeronshow.

"Aryl" means a cyclic, aromatic Deputy containing hydrogen and carbon, for example, phenyl, naphthyl and biphenyl.

"Cycloalkenyl" represents a monocyclic or polycyclic, unsaturated (have the tsya, at least one carbon-carbon double bond) Deputy containing carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl. Cyclohexenyl, cycloheptenyl, cyclooctyl, cyclodecyl, norbornyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthalen and octahydronaphthalene.

"Cycloalkanones" means cycloalkenyl, optionally containing carbon-oxygen single bond, for example, cyclobutylamine, cyclopentylamine, cyclohexasiloxane, cycloheptylamine, cyclooctylamine, cyclotetrasiloxane, norbornanamine, and bicyclo[2.2.2]octenylsuccinate.

"Cycloalkyl" represents a monocyclic or polycyclic, saturated Deputy containing carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, norbornyl, bicyclo[2.2.2]octyl and decahydronaphthalene.

"Cycloalkanes" means cycloalkyl, optionally containing carbon-oxygen single bond, for example, cyclopropylamino, cyclobutylamine, cyclopentylamine, cyclohexyloxy, cycloheptylamine, cyclooctylamine, cicadelloidea, norbornylene and bicyclo[2.2.2]aktionsgruppe.

"Halogen" represents fluorine, chlorine, bromine, and iodine.

"Halogen is lcil" means alkyl, optionally containing from one to the maximum possible number of, identical or different, by halogen, for example, vermeil, deformity, trifluoromethyl, 1-foretel, 2-foretel, 2,2,2-triptorelin, chloromethyl, trichloromethyl, and 1,1,2,2-tetraborate.

"Heterocyclyl" represents a cyclic Deputy, which may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where the above-mentioned heteroatom is a nitrogen, sulfur, or oxygen, for example, benzofuranyl, benzothiazolyl, benzisoxazole, benzoxazole, benzothiazyl, benzothiazolyl, cinnoline, furanyl, indazoles, indolyl, imidazolyl, isoindolyl, ethenolysis, isothiazolin, isoxazolyl, 1,3,4-oxadiazolyl, oxazolyl, oxazolyl, phthalazine, pyrazinyl, pyrazolyl, pyrazolyl pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, hintline, chinoline, honokalani, 1,2,3,4-tetrazolyl, thiazolyl, thiazolyl, thienyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl and 1,2,4-triazolyl.

DETAILED description of the INVENTION

The compounds of this invention have the following formula:

where:

(a) Ar1represents a

(1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, Anil, or

(2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl,

where mentioned substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O(C 1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop, substituted phenyl and substituted fenoxaprop,

where such substituted phenyl and substituted fenoxaprop have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop;

(b) Het represents - or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur, or oxygen, and where Ar1and Ar2are not in the ortho-position relative to each other (but may be in the meta or in the para-position, for example, in the case of 5-membered ring they are in the 1,3-position and 6-membered rings of them are located in the 1,3-position or in the 1,4-position), and where the above-mentioned heterocyclic ring may also be substituted by one or more substituents, independently selected from H, F, Cl, Br, I, CN, NO2, the carbonyl group, C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6the CEC is alkyl)and, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop, substituted phenyl and substituted fenoxaprop,

where such substituted phenyl and substituted fenoxaprop have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and ( 1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop;

(C) Ar2represents a

(1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or

(2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl,

where mentioned substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenate is)and, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop, substituted phenyl and substituted fenoxaprop (where such substituted phenyl and substituted fenoxaprop have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)and C(=O)(C 2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl and fenoxaprop;

(d) X1represents O or S;

(e) X2represents O or S;

(f) R4 represents H, C1-C6alkyl, C1-C6halogenated,3-C6cycloalkyl,3-C6halogenosilanes, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated), OSO2(C1-C6alkyl), OSO2(C1-C6halogenated), C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl), C(=O)O(C1-C6alkyl), C(=O)(C1-C6halogenated), C(=O)O(C1-C6halogenated), C(=O)(C3-C6cycloalkyl), C(=O)O(C3-C6cycloalkyl), C(=O)(C2-C6alkenyl), C(=O)O(C2-C6alkenyl), (C1-C6alkyl)O(C1-C6alkyl), (C1-C6alkyl)S(C1-C6alkyl), C(=O)(C1-C6alkyl)C(=)O(C 1-C6alkyl), phenyl, fenoxaprop,

where every traveler alkyl, halogenated, cycloalkyl, halogenosilanes, cycloalkanes, halogenocarboxylic, alkoxygroup, halogenlampe, alkenyl, quinil, phenyl, and fenoxaprop optionally substituted by one or more substituents, independently selected from F, Cl, Br, I, CN, NO2, the carbonyl group, C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6 alkyl)C(=O)O(C1-C6alkyl)and phenyl, and fenoxaprop;

(g) n=0, 1, or 2;

(h) Rxand Ryindependently selected from H, C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl)and phenyl, and fenoxaprop; and

(i) R1, R2 and R3 are independently selected from F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C2-C6alkenyl, C2-C the quinil, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, (C1-C6alkyl)O(C1-C6alkyl)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl)Oh, C(=O)phenyl, phenyl, C1-C6alkylphenyl, C(=O)fenoxaprop, fenoxaprop,1-C6alkylphenoxy, C(=O)Het-1, Het-1, or C1-C6Het-1,

where Het-1 is a 5 - or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen, and

where every traveler alkyl, halogenated, cycloalkyl, halogenosilanes, cycloalkanes, halogenocarboxylic, alkoxygroup, halogenlampe, alkenyl, quinil, phenyl, fenoxaprop, and Het-1, optionally substituted by one or more substituents, independently selected from F, Cl, Br, I, CN, NO2, the carbonyl group, C1-C6of alkyl, C1-C6ha is hogenakkal, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRy, (C1-C6alkenyl)NRxRy, (C1-C6quinil)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop, and Het-1,

where R1 and R2 together may not necessarily form a 3-12-membered saturated or unsaturated cyclic group that may contain one or more heteroatoms selected from nitrogen, sulfur, and oxygen (provided that such cyclic group has the Xia preferably no 1-O-link)where the above-mentioned cyclic group may bear one or more substituents independently selected from F, Cl, Br, I, CN, NO2, the carbonyl group, C1-C6of alkyl, C1-C6halogenoalkane, C3-C6cycloalkyl, C3-C6halogennitroalkane, C3-C6cycloalkanes, C3-C6halogenocarboxylic, C1-C6alkoxygroup, C1-C6halogenlampe, C2-C6alkenyl, C2-C6the quinil, S(=O)n(C1-C6alkyl), S(=O)n(C1-C6halogenated)and OSO2(C1-C6alkyl), OSO2(C1-C6halogenated)a, C(=O)H, C(=O)NRxRy, (C1-C6alkyl)NRxRyC(=O)(C1-C6alkyl)Oh, C(=O)O(C1-C6alkyl)Oh, C(=O)(C1-C6halogenated)Oh, C(=O)O(C1-C6halogenated)Oh, C(=O)(C3-C6cycloalkyl)Oh, C(=O)O(C3-C6cycloalkyl)Oh, C(=O)(C2-C6alkenyl)Oh, C(=O)O(C2-C6alkenyl)and (C1-C6alkyl)O(C1-C6alkyl)Oh, (C1-C6alkyl)S(C1-C6alkyl)Oh, C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), phenyl, fenoxaprop and Het-1.

In another embodiment, Ar1represents a substituted phenyl where the above-mentioned substituted phenyl has one or more C is mustiala, independently selected from C1-C6halogenoalkane and C1-C6halogenlampe.

In another embodiment, Het means triazolyl.

In another embodiment, Ar2represents phenyl.

In yet another embodiment, R4 indicates H or C1-C6alkyl.

In another embodiment, R1, R2 and R3 are independently selected from H, CN, C1-C6of alkyl, C1-C6halogenoalkane,3-C6cycloalkyl,2-C6alkenyl,2-C6the quinil, C(=O)O(C1-C6alkyl), phenyl, and Het-1.

In yet another embodiment, R1, R2 and R3 are independently selected from C1-C6of alkyl, C1-C6halogenoalkane,3-C6cycloalkyl,2-C6alkenyl,2-C6the quinil, C(=O)O(C1-C6alkyl), phenyl, and Het-1, each of which is substituted by one or more substituents, independently selected from F, Cl, Br, I, CN, NO2C1-C6of alkyl, C1-C6halogenoalkane, C1-C6alkoxygroup, S(=O)n(C1-C6alkyl)Oh, (C1-C6alkyl)NRxRy, (C1-C6alkenyl)NRxRy, (C1-C6quinil)NRxRyWith(=O)O(C1-C6alkyl)and phenyl.

In another embodiment, when R1, R2, and R3 before the represent Het-1, their independently selected from pyrimidinyl, pyridyl, chinoline, thiazolyl, teinila, furanyl, isoxazolyl, each of which may be optionally substituted.

In another embodiment, Het and Het-1 in the case when they have a nitrogen ring include a group (N+-O-).

Although these options were presented implementation other implementation options and combinations of these presents of embodiments and other embodiments are possible.

INTERMEDIATE TRAILING COMPOUNDS

The compounds of this invention is obtained by joining X2(C1)R1R2R3 to intermediate triazinone connection, Ar1-Het-Ar2through urethane or thiocarbamates N1(C=X1) (defined above). A wide range of trialling precursors can be used to obtain the compounds of this invention, provided that they contain a suitable functional group on Ar2. Suitable functional groups include an amino group, or a carboxylic acid group. These intermediate Triaryl connection can be obtained by methods previously described in the chemical literature. Several of these methods are described below.

Intermediate compounds, where 'Het' is a disubstituted pyridine, pyrimidine, pyrazin or ridazin, can be done with the use of combination reaction halogen or alkylthio-substituted pyridine, pyrimidine or pyrazine with arylboronic acid or borate ether complex, in terms of arilirovaniya Suzuki. See, for example, the following.

In the case of pyridines: Couve-Bonnaire et al.Tetrahedron2003, 59, 2793 and Puglisi et al.Eur. J. Org. Chem. 2003, 1552.

In the case of pyrazino: Schultheiss and BoschHeterocycles2003, 60, 1891.

In the case of pyrimidines: Qing et al.J. Fluorine Chem. 2003, 120, 21 and Ceide and MontalbanTetrahedron Lett. 2006, 47, 4415.

For 2,4-diaryl-pyrimidines: Schomaker and DeliaJ. Org. Chem. 2001, 66, 7125.

Thus, sequential palladium catalyzed reaction of arilirovaniya, using 4-formylphenyl-Bronevoy acid and 4-trifloromethyl-Bronevoy acid, can give essentially any circuit that is shown in the diagram below:

Just diaryl - pyridine and pyrazine and other dihalogenoalkane heterocyclic aromatic compounds can be obtained from dehalogenating pyridines and pyrazines and other dehalogenating heterocyclic aromatic compounds using a similar Protocol:

Halogen or alkylthio-pyrimidine and pyridine precursors are either commercially available or can be synthesized with the use of the cation ways, described in the literature (Rorig and Wagner U. S. Patent 3149109, 1964; Kreutzberger and TeschArzneim.-Forsch. 1978, 28, 235).

Connection, where 'Het' is a 1,3-diaryl-6-perfluoroalkyl-pyrimidine can be obtained in accordance with the following scheme. 2-Methylthio-substituted pyrimidine was allerban in the modified conditions of the Suzuki reaction (Liebeskind and Srogl Org. Lett. 2002, 4, 979), which gives 2-phenyl-pyrimidine, which were then restored to the corresponding anilines using, for example, palladium catalyst on a carbon carrier (Pd/C) in EtOH in the atmosphere of hydrogen.

Intermediate compounds, where 'Het' is a 1,3-disubstituted 1,2,4-triazole, can be obtained in accordance with one of the following schema.

Path A: 1,3-Diaryl 1,2,4-triazole were obtained from the corresponding-NH 3-aryl-1,2,4-triazoles, following the published route for N-arilirovaniya of imidazoles (Lin et al.J. Org. Chem. 1979, 44, 4160). The reaction mix 1,2,4-triazoles with aryl halides was performed in the heat treatment or, preferably, the microwave field (Antilla et al.J. Org. Chem. 2004, 69, 5578).

Path: Bromination of hydrazones with subsequent processing of bromhidrosis tetrazolo leads to the formation of 1,3-diaryl 1,2,4-triazole (Butler and FitzgeraldJ. Chem. Soc., Perkin Trans. 11988, 1587).

Path: Link is 1,2,4-triazole, in which the 5-position is optionally substituted alkyl or substituted alkyl group, can be obtained in accordance with the following scheme (Paulvannan and HaleTetrahedron2000, 56, 8071):

Connection, where 'Het' is an imidazole, can be obtained in accordance with one of the following ways:

Path A: (stage 1: Lynch et al.J. Am. Chem. Soc. 1994, 116, 11030. Stage 2: Liu et al.J. Org. Chem. 2005, 70, 10135):

Path: In the case of halogen-aryl groups, which also contain an activating group such as the nitro group or cyano group, the replacement of the aryl-halide-imidazole, using a base such as potassium carbonate in a polar aprotic solvent such asN,N-dimethylformamide (DMF) or dimethylsulfoxide (DMSO), can be performed as follows (Bouchet et al.Tetrahedron1979, 35, 1331):

Path: Following the method first described Porretta et al. (Farmaco,Edizione Scientifica1985, 40, 404),N-pencil-aniline is treated with potassium thiocyanate in an acidic medium (HCl), and the resulting 2-mercapto-imidazole then turn in desulfuromonas diaryl-imidazol by treatment with nitric acid in acetic acid.

Path D: N-Atilirovanie 4-bromoimidazo under microwave radiation (Path A, Hundred the Oia 2) provided the intermediate 1-aryl-4-bromoimidazo, which was converted into the intermediate Triaryl connection through processing aryl-baronowie by acid catalyzed by palladium conditions.

Connection, where 'Het' is a 1,4-disubstituted 1,2,3-triazole, can be obtained in accordance with the following scheme (Feldman et al.Org Lett. 2004, 6, 3897):

Connection, where 'Het' is a 3,5-disubstituted 1,2,4-triazole, can be obtained in accordance with the following scheme (Yeung et al.Tetrahedron Lett. 2005, 46, 3429):

Connection, where 'Het' is a 1,3-disubstituted 1,2,4-triazoline-5-it can be obtained in accordance with the following scheme (Pirrung and TepperJ. Org. Chem. 1995, 60, 2461 and LygaSynth. Commun. 1986,16, 163). (DPPA means diphenyl-phosphorylated):

Connection, where 'Het' is a 1,3-diaryl-pyrazolin, can be obtained in accordance with the following scheme. Monohydrazone of terephthalaldehyde handleN-chlorosuccinimide (NCS) in isopropyl alcohol (i-D), and the resulting chlorhydrate intermediate connection handle directly the base and substituted olefin with getting pyrazoline:

Connection, where 'Het' is a 3,5-disubstituted isoxazol, m which may be obtained in accordance with the following scheme:

Connection, where 'Het' is a 1,3-disubstituted pyrazole can be obtained in accordance with the following scheme. The reaction combinations of pyrazole with halogenated aromatic compounds was performed using the conditions of microwave radiation, described by Liu et al., The path And stage 2 above. (DMA is dimethylacetal.)

Connection, where 'Het' is a 2,4-disubstituted thiazole are obtained by condensation reaction thioamide with α-halo-acetophenone in proton solvent such as ethanol (e.g., Potts and MarshallJ. Org. Chem. 1976,41, 129).

Connection, where 'Het' is a 1,4-disubstituted 1,2,4-triazoline-5-he will receive in accordance with the following scheme (Henbach DE 2724819 A1, 1978 with a small change in the two stages):

Connection, where 'Het' is a 2,4-disubstituted oxazoline, get, starting from α-bromoacetophenone, in accordance with the following scheme (Periasamy et al.Synthesis2003, 1965 and Liu et al.J. Am. Chem. Soc. 2007, 129, 5834).

Connection, where 'Het' is a 2,5-disubstituted oxazoline is obtained in accordance with the following scheme (Favretto et al.Tetrahedron Lett. 2002,43, 2581 and Liu et al.J. Am. Chem. Soc. 2007, 129, 5834).

Connection, where 'Het' is a 1,4-disubstituted piperazine is obtained in accordance with the following scheme (Evans et al.Tetrahedron Lett. 1998, 39, 2937):

Connection, where 'Het' is a 1,3-disubstituted of pyrazolin receive the addition of aryl-hydrazine to β-dimethylamino-propiophenone as shown in the following diagram, which is described in the publication Linton et al. Tetrahedron Lett. 2007, 48, 1993, and in the publication of Wheatley et al. J. Am. Chem. Soc. 1954, 76, 4490. In addition to pyrazoline, a small proportion of bis-addition results in a corresponding dimethylaminomethyl-pyrazolin. These substances can be separated by chromatographic methods.

Connection, where 'Het' is a 3,5-disubstituted 1,2,4-triazine is obtained in accordance with the following scheme (Reid et al.Bioorg. Med. Chem. Lett. 2008, 18, 2455 and Saraswathi and SrinivasanTetrahedron Lett. 1971, 2315):

Connection, where 'Het' is a 2-getapiversion or 2,5-diketopiperazine get as in the following diagram. Ester nitrophenyl-glycine may be subjected to acylation using chloroacetyl-chloride, and intermediate N-chloracetophenone ester of glycine, in the processing of aniline undergoes substitution and cyclization at a temperature of from 120 to 180°C with the formation of diketopiperazine. Altern is effective, saturated or unsaturated, monoket-piperazines can be formed from the intermediate acetal connection, shown below, via hydrolysis and cyclization.

OBTAINING COMPOUNDS WITH (thio)URETHANE BOND

Connection with urethane or thio-urethane bond can be obtained from the corresponding aryl-amines by turning either the isocyanate or isothiocyanate or para-nitrophenyl-carbamate, followed by treatment of the corresponding alcohol (ROH) and organic or inorganic base in a suitable solvent, such as tetrahydrofuran (THF), at temperatures from 0 to 100°C. Alternatively, the carbamate can be obtained from chloroformiate formed from the alcohol (ROH) by processing triphosgene in the presence of a base, such as pyridine, followed by reaction with the appropriate amine.

The intermediate isocyanate compound can be obtained from the carboxylic acid by treatment with the use of azide source, such as diphenylphosphoryl-azide (DPPA). Can then be obtained utilised in order to expose his rearrangement of kurzius by heating to 110°C in toluene, and the resulting isocyanate can be treated with the appropriate alcohol and a base, as described above, in order to get the carbs is so Carboxylic acid precursor can be obtained by oxidation of the aldehyde, using conditions described in Example 18, through basic hydrolysis of the nitrile (for example, hydrolysis of 4-(1-(4-trifloromethyl)-1,2,4-triazole-3-yl)-benzonitrile that described in Example 10), or by acid hydrolysis of the nitrile using any of a variety of conditions described in the literature.

Carbamates can also be obtained using nitrophenyl-carbonate as shown below and demonstrated in the publication McClure and SieberHeteroat. Chem. 2000, 11, 192. The reaction of the tertiary carbinol with metallic potassium, followed by the addition of a para-nitrophenyl-chloroformate, provides the desired para-nitrophenylarsonic. Subsequent reaction of the carbonate with an amine in the presence of sodium carbonate in dimethylformamide provides the carbamate.

Alkenylboronic can be further functionalized by deprotonation by a base, such as n-butyl lithium, in a polar aprotic solvent such as tetrahydrofuran (THF), followed by reaction with etelcharge.com ensuring substituted alkyne.

Alkene-containing carbamates can be further option is analiziropany through hydroporinae-oxidation with the use of a complex of borane-dimethyl sulphide, with the subsequent processing of the tetrahydrate sodium perborate.

EXAMPLES

Examples are given for illustrative purposes and should not be construed as limiting disclosed in this document, the invention only variant implementation, the disclosures provided in these examples.

Source materials, reagents and solvents were obtained from commercial sources were used without additional purification. Anhydrous solvents were purchased as solvents Sure/Seal™ from Aldrich and were used not subjected after receiving any treatment. The melting points were obtained on capillary device for measuring the melting temperature Thomas Hoover Unimelt or through an automated system for measuring the melting temperature OptiMelt from Sanford Research Systems and are uncorrected.

Examples 1-55 illustrate additional molecules useful in the manufacture of various embodiments of this invention.

Example 1: Obtain 4-[1-(4-trifloromethyl)-1N-pyrrol-3-yl]-benzaldehyde

Stage 1. 1-(4-Trifloromethyl)-1H-pyrrole. Connection receive in accordance with the publication Colotta et al.J. Med. Chem.2006, 49, 6015. A solution of 4-trifloromethyl-amine (500 milligrams (mg), 2,82 millimoles(mmol), 1.00 equivalent (EQ.)) and 2.5-diethoxy-tetrahydrofuran (452 mg, 2.82 mmol, 1.00 equiv) in glacial acetic acid (20 milliliters (ml) is heated at 90°C for 1 hour (h) before drying on silica gel. Then the residue was transferred into a slurry in hexane, which is refluxed, filtered while hot and concentrated to dryness to provide the desired intermediate compound (519 mg, 81%).

Stage 2. 3-Bromo-1-(4-trifloromethyl)-1N-pyrrole. Connection receive in accordance with the publication Bray et al.J. Org. Chem. 1990, 55, 6317. To a solution of 1-(4-trifloromethyl)-1N-pyrrole (519 mg, to 2.29 mmol, 1.00 equiv.) in tetrahydrofuran (250 ml) at -78°C. add 0.05 M th solutionN-bromosuccinimide (NBS; 408 mg, to 2.29 mmol, 1.00 equiv.) in tetrahydrofuran for 45 minutes (min). The vessel is slowly heated to room temperature to obtain a crude Pomerol, with concentration, which, as shown by method GC-MS (Gas chromatography-Mass spectrometry), 55% of the desired intermediate. Substance use in subsequent reactions without further purification.

Stage 3. 4-[1-(4-Trifloromethyl)-1N-pyrrol-3-yl]-benzaldehyde. A suspension of crude 3-bromo-1-(4-trifloromethyl)-1N-pyrrole (356 mg, of 1.26 mmol, 1.00 equiv.) 4-formylphenylboronic acid (283 mg, 1,89 mmol, 1.50 equiv.) dichloride bis(Trife livostin)palladium(II) (27 mg, 0.04 mmol, 0.03 equiv.) 2 M aqueous solution of Na2CO3(of 1.26 ml, 2,52 mmol, 2.0 equiv.) and 1,4-dioxane (5 ml) and heat at 150°C in the reaction vessel, which is used in a microwave oven for 45 minutes. The cooled solution is then diluted with ethyl acetate (EtOAc) (20 ml), filtered through celite Celite®, concentrated to dryness, and purified by chromatography (2:2:1, hexane:EtOAc:acetone) to provide the desired intermediate compound (79 mg, 21%).

Example 2: Obtain 4-[1-(4-trifloromethyl)-4,5-dihydro-1N-pyrazole-3-yl]-benzaldehyde

Stage 1. 1-(4-Trifloromethyl)-pyrazolidine-3-one. Connection receive in accordance with the publication Rees and TsoiChem. Commun.2000, 415. A suspension of (4-trifloromethyl)-hydrazine-hydrochloride (300 mg, 1,32 mmol, 1.00 equiv.) 3-chloropropionitrile (167 mg, 1,32 mmol, 1.00 equiv.) and diisopropylethylamine on a polymer substrate (PS-DIEA) (1,30 grams (g), 5,28 mmol, 4,00 EQ) in THF (20 ml) was stirred at ambient temperature for 12 hours. Then the solution is filtered, concentrated to dryness and purified via chromatography (hexane:EtOAc:acetone, 2:2:1) to provide the desired intermediate compound (120 mg, 37%).

Stage 2. 3-Chloro-1-(4-trifloromethyl)-4,5-dihydro-1N-pyrazole: a General method is taken from the publication by Wang et al.Tetrahedron Lett. 2005, 46, 2631. To a solution of 1-(4-triptolemos is phenyl)-pyrazolidine-3-one (120 mg, 0.49 mmol, 1.00 equiv.) in toluene (20 ml) slowly add phosphorylchloride (22,5 mg, about 1.47 mmol, 3.00 EQ.). The mixture is then heat at 80°C for 1 hour before cooling to room temperature and decompose water (10 ml). The reaction mixture in the vessel is stirred in an atmosphere of nitrogen (N2within 8 hours before extraction of the product by EtOAc (200 ml), dried (MgSO4), and concentrate under reduced pressure. Method of gas chromatography-Mass spectrometry (GC-MS) confirms 88%formation of the desired intermediate compound, which is used in subsequent reactions without further purification.

Stage 3. 4-[1-(4-Trifloromethyl)-4,5-dihydro-1N-pyrazole-3-yl]-benzaldehyde: a Suspension of 3-chloro-1-(4-trifloromethyl)-4,5-dihydro-1N-pyrazole (114 mg, 0.43 mmol, 1.00 equiv.) 4-formylphenylboronic acid (97 mg, of 0.65 mmol, 1.50 equiv.) dichloride bis(triphenylphosphine)palladium(II) (10 mg, 0.01 mmol, 0.03 equiv.) 2 M aqueous solution of Na2CO3(of 0.43 ml, 0.86 mmol, 2.0 equiv.) and 1,4-dioxane (5 ml) and heat at 150°C in the reaction vessel, which is used in a microwave oven for 45 minutes. The cooled solution is then diluted with ethyl acetate (20 ml), filtered through celite Celite®, concentrated to dryness, and purified by chromatography (hexane: EtOAc:acetone, 2:2:1) to provide the desired intermediate compound (50 mg, 0.15 mmol, 31%).

p> Example 3: Obtaining 4-[1-(5-bromo-2-chlorophenyl)-1N-imidazol-4-yl]-benzonitrile

Connection receive in accordance with the publication of Liu et al.J. Org. Chem. 2005, 70, 10135. 4-(1H-Imidazol-4-yl)-benzonitrile (75 mg, 0.44 mmol; obtained from 4-(2-bromo-acetyl)-benzonitrile using the method of Lynch et al.J. Am. Chem. Soc. 1994,116, 11030), 4-bromo-1-chloro-2-iadanza (169 mg, 0,532 mmol), CsCO3(577 mg, 1.77 mmol), CuI (3 mg, of 0.013 mmol), 8-hydroxyquinoline (2 mg, of 0.013 mmol), and dimethylformamide/water (2 ml; solution 10:1) connect a 10-ml used in a microwave reaction vessel from the company's CEM, equipped with a magnetic stir bar and exposed to microwave radiation at 150°C for 30 minutes. Contents are then filtered and concentrated to dryness to provide intermediate compounds: 5-bromo-2-chlorophenyl-1H-imidazol-4-yl]-benzonitrile (68 mg, 43%).

Example 4: Obtain 4-[5-(4-propylphenyl)-isoxazol-3-yl]-benzonitrile

Stage 1. 4-(Gidroksilaminami)-benzonitrile. Connection receive in accordance with the publication Biasotti et al.Bioorg. Med. Chem. 2003,11, 2247. A suspension of 4-formylbenzoate (500 mg, 3,81 mmol, 1.00 equiv.) hydroxylamine-hydrochloride (290 mg, 4,19 mmol, 1,10 equiv.) and sodium acetate (1.56 g, 19,05 mmol, 5.00 equiv.) in methyl alcohol (50 ml) and heat at 70°C for 4 hours the first, than concentrating to dryness. The residue is then transferred to the suspension in diethyl ether (Et2O), filtered, and concentrated to provide the desired intermediate compound (496 mg, 3,39 mmol, 89%).

Stage 2. 4-(Hydroxyimino-methyl bromide)-benzonitrile. Connection receive in accordance with the publication Tanaka et al.Bull. Chem. Soc. Jpn. 1984,57, 2184. 0.05 M Solution of NBS (724 mg, 4.07 mmol, 1.20 EQ.) in dichloromethane is added dropwise at 0°C. to a solution of 4-(gidroksilaminami)-benzonitrile (496 mg, 3,39 mmol, 1.00 equiv.) in dichloromethane (50 ml). The solution is heated to room temperature to volumetric distribution for two different reaction to the vials. The contents of each ampoule is then concentrated and the crude residues used without further purification.

Stage 3. 4-[5-(4-Propylphenyl)-isoxazol-3-yl]-benzonitrile. A solution of 4-(hydroxyimino-methyl bromide)-benzonitrile (381 mg, 1.70 mmol), triethylamine (of 0.71 ml, 5,10 mmol, 3.0 equiv.) 1-ethinyl-4-propylbenzene (1,23 g, 8.50 mmol, 5.0 equiv.) in toluene (20 ml) and heat at 100°C for 1 hour before concentrating to dryness. Purification via normal phase chromatography provides the desired intermediate compound (108 mg, 22%).

Example 5: Receiving 4-{1-[4-(1-hydroxypropyl)phenyl]-1N-pyrazole-3-yl}-benzonitrile

Stage 1. 3-(4-Cyanophenyl)pyrazole. In cropton the Yu flask, equipped with stirrer and reflux condenser, add pair-cyanoacetate (5 g, 34,44 mmol) and dimethylformamide-dimethylacetal (DMF-DMA; 40 ml). The mixture is stirred at the boil under reflux for 5 hours prior to concentrating under reduced pressure providing crude dimethylamino-acryloylmorpholine intermediate compounds. Then the residue is suspended in a minimal volume of ethanol (~20 ml), load it hydrazine-monohydrate (1,67 ml, to 34.4 mmol)and heat at 80°C for 30 minutes before concentration. Crude 3-(4-cyanophenyl)pyrazol substance (5,59 g, 33 mmol, 96%), which emit has a purity sufficient for use in subsequent reactions.

Stage 2. 4-[1-(4-Propionyl phenyl)-1N-pyrazole-3-yl]-benzonitrile. 4-(1N-Pyrazole-3-yl)-benzonitrile (100 mg, 0,591 mmol), 1-(4-bromophenyl)-propane-1-he (126 mg, 0,591 mmol), Cs2CO3(770 mg, 2,364 mmol), CuI (4 mg, 0.018 mmol), 8-hydroxyquinoline (3 mg, 0.018 mmol)and a solution of dimethylformamide/water (2 ml; solution 10:1) connect a 10 mm used in a microwave reaction vessel from the company's CEM, equipped with a magnetic stirrer, and is exposed to microwave radiation at 150°C for 30 minutes. Contents are then filtered and concentrated to dryness to provide nitrile (158 mg, 0.508 mmol, 86%).

Example 6: Obtaining complex diethyl ether 5-(4-formylphenyl)-2-(4-trifloromethyl)-3,4-dihydro-2 N-pyrazole-3,4-dicarboxylic acid

Stage 1. Getting 4-[(4-trifloromethyl)-hydrazinophenyl]-benzaldehyde. Connection receive in accordance with the publication Paulvannan et al.Tetrahedron. 2000, 56, 8071. To a mixed solution of benzene-1,4-dicarbollide (1.50 g, and 11.2 mmol, 1.00 equiv.) isopropyl alcohol (250 ml) is added 4-triptoreline)phenylhydrazine hydrochloride (2.55 g, and 11.2 mmol, 1.00 equiv.) portions over 5 minutes. The solution was stirred at ambient temperature for 1 hour prior to concentration to dryness and purification using chromatography (hexane: EtOAc:acetone, 2:2:1), which gives an intermediate connection (2,48 g, 72%).

Stage 2. Synthesis of chloridazon. The intermediate connection receive in accordance with the publication Lokanatha Rai and HassnerSynth. Commun. 1989,19, 2799. A solution of 4-[(4-trifloromethyl)-hydrazinophenyl]-benzaldehyde (2,48 g, with 8.05 mmol, 1.00 equiv.) andNchlorosuccinimide (1,61 g, 12,08 mmol, 1.5 EQ.) isopropyl alcohol (100 ml) and heat at 80°C for 1 hour. Then the solution is cooled and volumetric distributed equally between the six different reaction vessels according to 1.34 mmol of intermediate compounds in each vessel.

Stage 3. Synthesis of pyrazoline. Obtain the connection according to the publication Paulvannan et al.Tetrahedron2000,56, 8071. In each reaction OSD add triethylamine (of 0.56 ml, 4.02 mmol, 3.00 EQ.) and the corresponding acrylates (6,70 mmol, 5.00 EQ.). Then the reaction mixture is warm at 70°C for 90 minutes prior to concentration to dryness and purification using chromatography (hexane:ethyl acetate:acetone, 2:2:1).

Example 7: Getting 4-{1-[4-(2,2,2-triptoreline)-phenyl]-1N-imidazol-4-yl}-benzonitrile

4-(2-Bromoacetyl)-benzonitrile (58 mg, 0.21 mmol) and 4-(2,2,2-triptoreline)-phenylamine (50 mg, 0.21 mmol) are combined in 100-ml Erlenmeyer flask with a magnetic stir bar. The contents dissolved in ethanol (1 ml) and stirred at ambient temperature for 2 hours. Then the crude intermediate compound is transferred into a 100-ml round bottom flask containing KSCN (21 mg, 0.21 mmol) and conc. HCl (18 μl, 0.21 mmol). The vessel warm at 80°C for 1 hour before pouring its contents into 5 ml of a solution of H2O/NH4OH (1:1). The solution is allowed to stand for 24 hours and then the solid is filtered off and washed with simple ether to provide intermediate imidazolyl (32 mg, 0,086 mmol, 33%). An aqueous solution of HNO3(1.35 ml, 0,387 mmol) and KNO3(1 mg, of 0.003 mmol) is then added dropwise during 10 minutes to a suspension imidazolidine in acetic acid (2 ml). After stirring for 2 hours at ambient temperature the Reda solution was poured into crushed ice and neutralized (pH=7) of 0.1 N-s ' solution of sodium hydroxide (NaOH, water). Nitrile allocate vacuum filtration and dried at 45°With Noah vacuum oven for 12 hours (23 mg, 78%), melting point 179°C.

Example 8: Obtain 4-[1-(4-propylphenyl)-1N-imidazol-4-yl]-benzonitrile

4-Propylaniline (2.70 g, 20 mmol) is added dropwise to a solution of 4-cyanobenzyl-bromide (2.20 g, 10 mmol) in dimethylformamide (5 ml). This solution is then added to a hot (180°C) formamide (20 ml) for 5 minutes, and the combined solution is kept mixed at 180°C for 2 hours. The cooled solution is then poured into ice (100 ml), and extracted with simple ether (2×75 ml). After drying and concentrating, the resulting dark oil is purified by chromatography (hexane:ethyl acetate:dichloromethane, 3:1:2). The first product (510 mg) identified as 4-(5-propyl-1N-indol-3-yl)-benzonitrile, melting point 140°C. the Second fraction (275 mg) identify as desired imidazole: melting point 133°C;

1H NMR (400 MHz, CDCl3) δ of 7.95 (d, J=6 Hz, 2H), of 7.90 (s, 1H), of 7.70 (d, J=6 Hz, 2H), 7,68 (s, 1H), 7,38 (d, J=4 Hz, 2H), 7,31 (d, J=4 Hz, 2H), 2,69 (t, J=8,9 Hz, 2H), by 1.68 (m, 2H), and 0.98 (t, J=7.5 Hz, 3H);

ESIMS m/z grass 288,1 (M+H); ESIMS (Mass spectrometry by ionization method elektrorazpredelenie)m/zGRASS 288,1 (M+H).

Example 9: Obtain 4-[1-(4-trifloromethyl)-1N-imidazol-4-yl]-benzonitrile

4-Cryptomaterial (2.20 g, 12.4 mmol) is added dropwise to a solution of 4-cyanobenzyl-bromide (1.50 g, 6.7 mmol) in dimethylformamide (5 ml). This solution is then added to a hot (180°C) formamide (20 ml) for 5 minutes, and the combined solution is kept mixed at 180°C for 2 hours. The cooled solution is then poured on ice (100 ml), and extracted with simple ether (2×75 ml). After drying and concentrating, the resulting semi-solid substance is recrystallized from MeOH/H2O. a Second recrystallization from MeOH/H2O removes trace amounts formanilide impurities and provides clean product (200 mg): melting point 155°C. Analysis: Calculated for C17H10F3N3O: C, 62,01; H, A 3.06; N, OF 12.76. Found: C, 61,53; N, 3,13; N, 12,55.

Example 10: Obtain 4-[1-(4-trifloromethyl)-1N-imidazol-4-yl]-benzoic acid

A solution of nitrile (1.1 g, 3.3 mmol) in ethanol (5 ml) and water (2 ml) is treated with sodium hydroxide (1 g, 20 mmol)and the solution warm to boiling under reflux for 6 hours. Then it is cooled and acidified with 1N-s ' solution of HCl, and the resulting white solid is filtered and dried in air, giving acid (1.1 g) as a light gray solid: melting point 230°C;

1 H NMR (400 MHz, CDCl3) δ of 11.4 (s, 1H), of 7.90 (d, J=6,4 Hz, 2H), 7,89 (s, 1H), 7,80 (d, J=8.6 Hz, 2H), 7,63 (d, J=1.3 Hz, 1H), 7,49 (d, J=9,3 Hz, 2H), 7,38 (d, J=8,9 Hz, 2H).

Example 11: Obtain 4-[4-(4-triptoreline)-1N-imidazol-1-yl]-benzonitrile

4-Triptoreline-imidazole (4.0 g, 19 mmol), 4-perbenzoate (1.2 g, 8.5 mmol) and potassium carbonate (1.5 g, 10.9 mmol) are combined in dimethyl sulfoxide (15 ml) and heat at 100°C for 6 hours. The cooled solution is then poured into water (100 ml)and the resulting solid filtered and dried in air, giving imidazol-nitrile (4,65 g) as a white solid: melting point 252°C;

1H NMR (300 MHz, CDCl3) δ 8,05 s, 1H), 7,95 (d, J=8 Hz, 2H), a 7.85 (d, 2 H), 7,72 (s, 1H), 7,72 (d, J=8 Hz, 2 H), a 7.62 (d, J=8 Hz, 2H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z314,1 (M+H). Analysis: Calculated for C16H10F3N3O2: C, 65,18; H, UP 3.22; N, 13,41. Found: C, 64,49; N, 3,23; N, 13,08.

Example 12: Obtain 4-bromo-1-(4-trifloromethyl)-1N-imidazole

In a round bottom flask is charged with 4-bromoimidazo (1,15 g, 7,81 mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol), cesium carbonate (3,39 g, 10.4 mmol) and 4-triftormetilfullerenov (1.50 g, to 5.21 mmol). The mixture (10:1) of dimethylformamide (15 ml) and water (1.5 ml) are added to the reaction mixture, and the solution heated the Ute up to 130°C for 4 hours. The reaction mixture was then diluted with ethyl acetate and washed successively with water, ammonium chloride (saturated solution), water and sodium bicarbonate. Organic compounds dried over MgSO4, filtered and purified on a column of reversed phase that gives the imidazole (820 mg) as a white solid: melting point 139-141°C.; ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z308,0 (M+H).

Example 13: Obtain 4-methoxy-2-[1-(4-trifloromethyl)-1N-imidazol-4-yl]-benzaldehyde

4-Bromo-1-(4-trifloromethyl)-1N-imidazole (100 mg, 0,326 mmol), 2-formyl-5-methoxyflavanone acid (73 mg, 0.41 mmol), dichloride, bis(triphenylphosphine)palladium (2 mg, of 0.003 mmol), sodium bicarbonate (49 mg, 0.59 mmol) and a solution of DME/H2O, 1:1 (8:8 ml) are combined and added to the vessel, which is used in a microwave oven. The reaction mixture warm in a microwave oven with stirring at 100°C for 12 minutes. To achieve 100°C in a microwave oven requires 5 minutes, then microwave support at 100°C for 12 minutes, and then cooled. Analysis by thin layer chromatography (TLC) (ethyl acetate:cyclohexane, 1:1) shows the presence of the original substance, therefore the sample is heated to 100°C for an additional 8 minutes. When cooling is formed sieges is to; it is filtered off and washed with water, giving a grey solid (86 mg): ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z363,0 (M+H).

The following intermediate substance is also obtained using this technique:

Example 14: Getting 2-fluoro-4-[1-(4-trifloromethyl)-1N-imidazol-4-yl]-benzaldehyde

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z351,0 (M+H).

Example 15: Obtain 4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzonitrile

Stage 1. 4-(1N-[1,2,4]Triazole-3-yl)-benzonitrile. Uses a common methodology outlined by the author: Lin et al. J. Org. Chem. 1979, 44, 4163, to obtain 3-(4-nitrophenyl)-1N-[1,2,4]triazole. 4-Cyanobenzene (21,63 g, 0,148 mol) is dissolved in a mixture of DMF-DMA (100 ml) and stirred at boiling under reflux in nitrogen atmosphere for 8 hours. The mixture is concentrated to dryness and suspended in acetic acid (AcOH, 50 ml). Then in a vessel load of hydrazine-monohydrate (7,18 ml, 0,148 mmol) and stirred at the boil under reflux for 1 h before concentration. Get the desired 4-(1H-[1,2,4]triazole-3-yl)-benzonitrile with a purity of 98% by grinding into powder with diethyl ether followed by filtration (12,17 g, 0,072 mol, 48%).

Stage 2. 4-[1-(4-Trift methoxyphenyl)-1 N-[1,2,4]triazole-3-yl]-benzonitrile. Triazole (70 mg, 0.41 mmol), 1-iodine-4-cryptomaterial (142 mg, 0,493 mmol), CsCO3(535 mg, 1,644 mmol), CuI (3 mg, 0.012 mmol), 8-hydroxyquinoline (2 mg, 0.012 mmol)and a solution of DMF/H2O (2 ml), a solution of 10:1) are combined into 10-ml used in a microwave reaction vessel from the company's CEM, equipped with a magnetic stirrer, and is exposed to microwave radiation at 150°C for 30 minutes. Then, the contents filtered and concentrical dry with the provision of the intermediate 1,3-diphenyl-triazole compound (18 mg, 13%).

Example 16: Obtain 4-[1-(4-pentafluoroethanesulfonyl)-1N-[1,2,4]triazole-3-yl]-benzonitrile

Stage 1. 1-Bromo-4-pentafluoroethanesulfonyl. The connection specified in the title, is obtained using conditions perftoruglerodnye, originally described in the publication: Popov et al.J. Fluorine Chem. 1982, 21, 365. To a solution of 4-bromobenzoyl (500 mg, of 2.64 mmol, 1.00 equiv.) and chloride of triethylenediamine (60 mg, 0.26 mmol, 0.10 EQ.) in 10 ml of an aqueous solution of a mixture of Et2O/NaOH 1:1 (25%aqueous solution) at 0°C bubbled gas, 1,1,1,2,2-pendaftar-2-Iodate within 30 minutes (>5 EQ.). During this period of time the UV lamp is directed to the reaction vessel, while the temperature is maintained below 10°C. by use the of intermittent ice bath. The contents are then heated to room temperature, extracted with diethyl ether (300 ml), dried (MgSO4), and concentrate under reduced pressure. Part of this crude material is used in subsequent reactions without further purification (remainder 200 mg: product 120 mg, 0,39 mmol, 1.2 EQ.).

Stage 2. 4-[1-(4-Pentafluoroethanesulfonyl)-1N-[1,2,4]triazole-3-yl]-benzonitrile. The reaction mix with 4-(1N)-[1,2,4]triazole-3-yl)-benzonitrile described above, gives 4-[1-(4-pentafluoroethanesulfonyl)-1N-[1,2,4]triazole-3-yl]-benzonitrile (70 mg, 46%).

Example 17: Obtain 4-[1-(4-panafcortelone-phenyl)-1N-[1,2,4]triazole-3-yl]-benzaldehyde

Stage 1. A solution of 3-para-tolyl-1N-[1,2,4]triazole (4,85 g of 30.5 mmol), 4-bromophenyl-panafcortelone ether (10.0 g, to 34.4 mmol), Cs2CO3(25 g, 77 mmol), CuI (1.25 g, 6.5 mmol) and 8-hydroxyquinoline solution (0.35 g, 2.4 mmol) in a mixture of DMF/H2O 9:1 (50 ml) was vigorously stirred and heated to 130°C. (internal temperature) for 20 hours. Then the solution is cooled, poured into water, and acidified with 2N-s ' solution of HCl to pH 2. Then add ether (250 ml)and the solution shaken and filtered before separating layers. The organic layer is dried and concentrated, and the resulting kameneobrobnij solid warm with a mixture of hexanol (100 ml). Layer with hot hexane CTD is collected by decanting from the insoluble residue, the resulting solution is cooled to 0°C and the precipitated solid is filtered off and air-dried to provide 1-(4-panafcortelone-phenyl)-3-para-tolyl-1N-[1,2,4]triazole (7.0 g, 61%, based on the original triazole) in a solid off-white color: melting point 130-132°C.; ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z370,8 (M+H).

Stage 2. The product of Stage 1 (7.0 g, to 18.7 mmol) dissolved in acetonitrile (200 ml) and stirred at ambient temperature, while the nitrate of cerium ammonium (32 g, 58 mmol) in water (60 ml) is added in portions during 10 minutes. Then the solution is heated to boiling point, which is carried out under reflux for 4 hours, cooled, and diluted with water (200 ml). The solution is extracted with simple ether (2×200 ml)and the combined organic layer is dried and concentrated, giving an orange oil. This substance is dissolved in dioxane (40 ml) and treated with a solution of KOH (5 g, 90 mmol) in water (20 ml). The solution is heated to boiling point, which is carried out under reflux for 2 hours, then cooled and diluted with water (100 ml). Aldehyde precipitates, and it is collected by filtration. Recrystallization from a mixture of MeOH/H2O give pure aldehyde in the form of a solid white color (2.2 g, 30%): the temperature is and melting 137-144°C.

1H NMR (300 MHz, CDCl3) δ a 10.1 (s, 1H), 8,65 (s, 1H), 8,40 (d, J=8,4 Hz, 2H), and 8.0 (d, J=8,4 Hz, 2H), a 7.85 (d, J=9 Hz, 2H), 7,45 (d, J=9 Hz, 2H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z384,2 (M+H).

Example 18: Obtain 4-[1-(4-panafcortelone-phenyl)-1N-[1,2,4]triazole-3-yl]-benzoic acid

A solution of 4-[1-(4-panafcortelone-phenyl)-1N-[1,2,4]triazole-3-yl]benzaldehyde (1.7 g, 4.4 mmol), sodium bromate (2.1 g, a 13.9 mmol) and sodium bisulfate (of 0.53 g, 4.5 mmol) in acetonitrile (50 ml) is heated to the boiling point, which is carried out under reflux for 5 hours, during which formed a voluminous precipitate. Then the solution is cooled and poured into water (100 ml), filtered, and dried to provide the acid (1,67 g) as a white solid: melting point 225°C;

1H NMR (300 MHz, CDCl3) δ a 10.1 (s, 1H), 8,63 (s, 1H), 8,35 (d, J=8,4 Hz, 2H), 8,5 (d, J=8,4 Hz, 2H), a 7.85 (d, J=9 Hz, 2H), 7,43 (d, J=9 Hz, 2H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z399,2 (M+H).

Example 19: Obtaining 4-[1-(4-panafcortelone-phenyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide

A solution of 4-[1-(4-panafcortelone-phenyl)-1N-[1,2,4]triazole-3-yl]benzoic acid (1,67 g, 4.2 mmol), diphenylphosphinite (1.26 g, 4,58 mmol) and triethylamine (0.5 g, 5 mmol) in anhydroustert-b is tilava alcohol (10 ml) is heated to 75°C for 90 minutes, which leads to the dissolution of the original acid and subsequent precipitation of the azide. The cooled solution is then poured on ice (10 g), and the resulting mixture is filtered and dried to provide azide (0,80 g) as a white solid: melting point 112-115°C With decomposition;

1H NMR (300 MHz, CDCl3) δ to 8.62 (s, 1H), with 8.33 (d, J=8,4 Hz, 2H), 8,16 (d, J=8,4 Hz, 2H), a 7.85 (d, J=9 Hz, 2H), 7,42 (d, J=9 Hz, 2H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z425 (M+H).

Example 20: Obtaining 4-[1-(4-butylphenyl)-1N-[1,2,4]triazole-3-yl]-benzonitrile

A solution of 4-n-butyl-phenyl hydrazine (1.0 g, 5 mmol) and 4-cyanobenzaldehyde (0.8 g, 6.0 mmol) infrom-propyl alcohol (15 ml) is heated on a steam bath for 2 hours and then cooled and diluted with water (5 ml). The resulting solid orange color is filtered off and dried in the air, which gives the hydrazone (1.30 grams) in a solid yellow color, with a melting point of 107°C. a Solution of the hydrazone (1.1 g, 4.0 mmol) and NCS (of 0.67 g, 5 mmol) infrom-propyl alcohol (20 ml) is stirred under nitrogen atmosphere at ambient temperature for 2 hours, during which the initial solid is dissolved, and a new solid formed. The resulting orange solution then is srabatyvayut tetrazole (0.45 g, 6.4 mmol) and triethylamine (960 μl, 7.0 mmol). The solution is orange-brown color warm while boiling under reflux for 2 hours. Then the solution is cooled, diluted with water (25 ml), extracted with ethyl acetate, dried, concentrated, and purified by chromatography (Biotage, hexane:ethyl acetate 4:1), which gives triazole (0,42 g, 35%) as a solid off-white color: melting point 124°C;

1H NMR (300 MHz, CDCl3) δ 8,58 (s, 1H), with 8.33 (d, J=8 Hz, 2H), 7,78 (d, J=8 Hz, 2H), to 7.64 (d, J=8,2 Hz, 2H), 7,33 (d, J=8,2 Hz, 2H), 2,70 (t, J=7.8 Hz, 2H), and 1.63 (m, 2H), 1,38 (m, 2H), of 0.95 (t, J=7.5 Hz, 3H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z303,1 (M+H).

Example 21: Obtain 4-[1-(4-pentafluoroethyl-phenyl)-1N-[1,2,4]triazole-3-yl]-benzaldehyde

Stage 1. 1-(4-Pentafluoroethyl-phenyl)-3-para-tolyl-1N-[1,2,4]triazole. Pentafluoroethyl-iodide (521 mg, 2,12 mmol) condense in a vial containing 1-bromo-4-iadanza (300 mg, 1.06 mmol), copper powder(0) (135 mg, 2,12 mmol), and dimethylsulfoxide (5 ml). Then the ampoule is sealed (sealed) and exposed to microwave radiation at 150°C for 60 minutes. Analysis by gas chromatography-mass spectrometry showed the expenditure of the original substance, which gives 1-bromo-4-pentabromoethylbenzene and 1-iodine-4-pentabromoethylbenzene intermediate compounds. CME is ü (1.06 mmol) is transferred into a 250-ml round bottom flask and add 3- pair-tolyl-1N-[1,2,4]triazole (169 mg, 1.06 mmol), Cs2CO3(1,38 g, 4,24 mmol), CuI (202 mg, 1.06 mmol), 8-hydroxyquinoline (2 mg, to 0.011 mmol)and a solution of DMF/H2O (12 ml; solution 10:1). The solution is stirred at the boil under reflux at 160°C for 6 hours. Upon completion, the cooled contents poured into water and allowed to settle for 1 hour. The precipitate is collected by vacuum filtration and dried overnight in a vacuum oven at 45°C. the Crude intermediate 1-(4-pentafluorophenyl)-3-pair-tolyl-1N-[1,2,4]triazole compound used in step 2 without further purification.

Stage 2. Oxidation to the aldehyde. Nitrate of ammonium cerium(IV) (3,32 g, 4,24 mmol) and intermediate compound from step 1 are combined in round bottom flask with acetonitrile and water (20 ml; 1:1). The solution is stirred at the boil under reflux at 110°C for 4 hours, which provides a mixture of 3-(4-nitroxymethyl-phenyl)-1-(4-pentafluoroethyl-phenyl)-1N-[1,2,4]triazole and 4-[1-(4-pentafluoroethyl-phenyl)-1N-[1,2,4]triazole-3-yl]-benzaldehyde intermediates. The acetonitrile removed in vacuo, and precipitation of the crude intermediate compounds collected by filtration. The substance is then combined with the powder KOH (178 mg, 3,18 mmol) in dioxane and water (10 ml; 1:1) and stirred at boiling under reflux at 105°C for 90 minutes before UDA is Aut dioxane in vacuo, that gives the precipitation of the intermediate compounds from the water. 4-[1-(4-Pentafluoroethyl-phenyl)-1N-[1,2,4]triazole-3-yl]-benzaldehyde intermediate compound collected by filtration (35 mg, 0,095 mmol, 9% of 4-tolyl-triazole).

Example 22: Obtain 4-[3-(4-formyl-phenyl)-[1,2,4]triazole-1-yl]-phenyl ether complex of triftoratsetata.

Stage 1. 1-(4-Methoxyphenyl)-3-pair-tolyl-1N-[1,2,4]triazole obtained by reaction mix 3-pair-tolyl-1N-[1,2,4]-triazole (4-yoganidra under the conditions described for Stage 1 of the previous example. This substance is then Demetriou using the conditions described in the publication: Hitchcock et al.Synlett2006, 2625. To a solution of 1-(4-methoxyphenyl)-3-pair-tolyl-1N-[1,2,4]triazole (300 mg, 1.28 mmol) in dichloromethane (10 ml) at 0°C under nitrogen atmosphere is added dropwise tribromide boron (1 M th solution in hexane; 1,67 ml, a rate of 1.67 mmol). Upon completion of the addition, the vessel is heated to ambient temperature, then refluxed at 40°C for 6 hours. The cooled contents are then degraded water before removing dichloromethane and distribution between ethyl acetate and water. The organic layer is collected, washed with brine, dried (MgSO4), concentrated, and purified by chromatography (hexane:ethyl acetate:acetone 3:1:1) providing premiato the nogo 4-(3- pair-tolyl-[1,2,4]triazole-1-yl)-phenol compound (219 mg, 0,872 mmol, 68%). The anhydride of triftoratsetata (0.16 ml, 0.96 mmol) is added dropwise to a solution of phenol and 4-tert-butyl-2,6-dimethylpyridine (142 mg, 0,872 mmol) in dichloromethane (10 ml) at 0°C under nitrogen atmosphere. The vessel is heated to ambient temperature before removing the solvent under reduced pressure and purification of the residue by chromatography (hexane:ethyl acetate:acetone, 2:2:1) to provide intermediate compound, 4-(3-pair-tolyl-[1,2,4]triazole-1-yl]-phenyl ether complex of triftoratsetata (304 mg, 0,794 mmol, 91%).

Stage 2. Oxidation of the above intermediate 4-methyl compounds to the corresponding aldehyde is carried out using ammonium nitrate cerium(IV) in the conditions described for step 2 in the previous example.

Example 23: Obtain 4-[5-(4-triptoreline)-1N-[1,2,4]triazole-3-yl]-benzonitrile

Terephthalonitrile (115 mg, 0.90 mmol), hydrazide 4-triftorperasin acid (92 mg, 0,450 mmol), K2CO3(31 mg, 0,225 mmol), andn-butyl alcohol (~2 ml) connect a 10-ml used in a microwave reaction vial from CEM, equipped with a magnetic stirrer, and is exposed to microwave radiation at 150°C for 30 minutes. Then the content is imoe filtered and concentrated to dryness. Chromatography (hexane:ethyl acetate, 3:1) provides 1,2,4-triazole-nitrile (72 mg, 0,230 mmol, 51%).

Example 24: Obtain 4-[1-(3,4-dichlorophenyl)-5-oxo-4,5-dihydro-1N-[1,2,4]triazole-3-yl]-benzonitrile

Stage 1. 4-Cyanophenyl-oxo-acetic acid. In a round bottom flask, equipped with a mechanical stirrer and reflux condenser loadpair-cyanoacetate (5 g, 34,44 mol), SeO2(of 9.55 g,86,1 mmol), and pyridine (~100 ml). The mixture is stirred while boiling under reflux for 6 hours, then remove the air filter and loaded into the filtrate with 10%aqueous HCl solution (20 ml). The filtrate is extracted into ethyl acetate (3×50 ml)and the combined organic layers are additionally extracted in an almost saturated solution of NaHCO3. The aqueous layer was then carefully acidified (pH 1) with concentrated hydrochloric acid, which gives a small amount of the desired product. The remaining oxo-acetic acid is removed by extraction into ethyl acetate, drying (MgSO4), and concentration (1,69 g, 28%).

Stage 2. 4-[1-(3,4-Dichlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]-triazole-3-yl]-benzonitrile. A suspension of 4-cyanophenyl-oxo-acetic acid (100 mg, 0,571 mmol), hydrochloride (3,4-dichlorophenyl)hydrazine (122 mg, 0,571 mmol), 12,1 N-th HCl solution (5 μl, 0,057 mmol), and water (~10 ml) in 25-ml reaction tube energidepartementet at ambient temperature for 24 hours. Get hydrazone vacuum filtration and placed in a 100-ml round bottom flask with a magnetic stirrer. Then the flask was added triethylamine (0,08 ml, 0,571 mmol), diphenylphosphoryl (157 mg, 0,571 mmol), and toluene (20 ml), then heated at 110°C for 1 hour. After cooling, the contents decompose 10%aqueous NaOH solution and acidified (pH 1) with concentrated hydrochloric acid. The precipitate allowed to settle for 15 minutes before getting intermediate connection vacuum filtration and dried overnight in a vacuum oven at 45°C (16 mg, 8%).

Example 25: Obtain 4-[1-(4-Chlorophenyl)-1N-[1,2,3]triazole-4-yl]-benzonitrile

Following the method published by Feldman et al. (Org Lett. 2004,6, 3897), suspension 4-ethynylbenzoate (50 mg, 0,393 mmol), 1-chloro-4-yogashala (94 mg, 0.393 mmol), L-Proline (9 mg, 0,079 mmol), ascorbic acid (7 mg, 0,039 mmol), NaN3(31 mg, 0,472 mmol), CuSO4(3 mg, at 0.020 mmol), and Na2SO4(11 mg, 0,079 mmol) in dimethyl sulfoxide (1.5 ml) and heat at 65°C for 24 hours. After cooling, the mixture is diluted with water and stirred for 30 minutes at ambient temperature. Then the intermediate 4-[1-(4-chlorophenyl)-1N-[1,2,3]-triazole-4-yl]-benzonitrile (54 mg, 48%) receive vacuum filtration after washing with excess amounts of water and a 20%solution of NH4 OH (~20 ml).

Example 26: Obtain 4-[5-(4-triptoreline)-tetrazol-2-yl]-benzaldehyde

This aldehyde is obtained from 4-triftormetilfullerenov, following the path described in the publication: Roppe et al.J. Med. Chem. 2004, 47, 4645.

Example 27: Obtain 4-[5-(4-trifloromethyl)-pyridine-3-yl]-benzaldehyde

Stage 1. 3,5-Dibromopyridine (4.4 mmol), 4-trifloromethyl-Bronevoy acid (5.1 mmol), tetrakis(triphenylphosphine)palladium(0) (0.04 mmol), 2 M-s ' solution of potassium carbonate (8,44 mmol) and dioxane (21 ml) are combined in a test tube and warm by means of microwave radiation for 10 minutes at 150°C. the Reaction mixture was washed away by a simple ether and washed with brine. Layer with simple ether is dried over magnesium sulfate, filtered, and removed solventin the vacuum. The crude mixture is purified by chromatography on silica gel, which gives 3-bromo-5-(4-trifloromethyl)-pyridine (130 mg) as a yellow solid:

1H NMR (400 MHz, CDCl3) δ 8,71 (m, 2H), 8,00 (t, J=2.1 Hz, 1H), 7,58 (d, J=8,8 Hz, 2H), 7,34 (d, J=8.0 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact) m/z 317 (M+).

Stage 2. The connection is obtained by catalyzed by palladium arilirovaniya product of stage 1 through 4-formylphenyl-Bronevoy acid.

Example 28: Obtain 4-[4-(4-triptime is oxiranyl)-pyridine-2-yl]-benzaldehyde

Stage 1. The connection is obtained by catalyzed by palladium arilirovaniya 2-chloro-4-iopidine through 4-trifloromethyl-Bronevoy acid.

Stage 2. 2-Chloro-4-(4-trifloromethyl)-pyridine (0.55 mmol), obtained from 2-chloro-4-iopidine, 4-formylphenyl-Bronevoy acid (0.82 mmol), tetrakis(triphenylphosphine)palladium(0) (for example, 0.005 mmol), 2 M-s ' solution of potassium carbonate (0,55 ml) and dioxane (3 ml) are combined in a test tube and irradiated with microwaves for 15 minutes at 150°C. the Reaction mixture was washed with ethyl acetate and washed with brine. The organic layer is dried over magnesium sulfate, filtered, and removed solventin the vacuum. Purification by chromatography on silica gel (ethyl acetate/hexane) gives the product (120 mg) as a solid off-white colors:

1H NMR (400 MHz, CDCl3) δ 10,11 (s, 1H), 8,81 (d, J=4,8 Hz, 1H), 8,24 (d, J=8.7 Hz, 2H), 8,03 (d, J=8,4 Hz, 2H), of 7.96 (m, 1H), 7,73 (d, J=9.0 Hz, 2H), 7,49 (DD, J=5,3, 1.8 Hz, 1H), 7,37 (d, J=8.1 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z343 (M+).

Example 29: Obtain 4-[6-(4-trifloromethyl)-pyridine-2-yl]-benzaldehyde

Stage 1. 4-(6-Bromopyridin-2-yl)-benzaldehyde (0.31 mmol) are obtained as shown in the publication: Puglisi et al.Eur. J. Org. Chem. 2003,8, 1552 - 1558.

Stage 2. 4-[6-(4-Trifloromethyl)-pyridine-2-yl]-be soldered. 4-(6-Bromo-pyridine-2-yl)-benzaldehyde (0.31 mmol), 4-trifloromethyl-Bronevoy acid (0.46 mmol), tetrakis(triphenylphosphine)palladium(0) (0,003 mmol), 2M potassium carbonate solution (0,31 ml) and dioxane (2 ml) are combined in a test tube and irradiated with microwaves for 10 minutes at 150°C. the Reaction mixture was washed away by a simple ether and washed with brine. The organic layer is dried over magnesium sulfate, filtered, and removed solventin the vacuum. Purification by chromatography on silica gel (ethyl acetate/hexane) gives the product (80 mg) as a solid off-white color: melting point 109-112°C;

1H NMR (400 MHz, CDCl3) δ 10,11 (s, 1H), 8,32 (d, J=8.5 Hz, 2H), 8,19 (d, J=8.1 Hz, 2H), 8,03 (d, J=8,4 Hz, 2H), 7,89 (t, J=7.9 Hz, 1H), 7,79 (d, J=7.7 Hz, 1H), 7,74 (d, J=8.0 Hz, 1H), 7,35 (d, J=8,3 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z343 (M+).

Example 30: Obtain 4-[6-(4-trifloromethyl)-pyrimidine-4-yl]-benzaldehyde

Stage 1. 4-Chloro-6-(4-trifloromethyl)-pyrimidine is obtained by catalyzed by palladium arilirovaniya 4,6-dichloropyrimidine through 4-trifloromethyl-Bronevoy acid:

1H NMR (400 MHz, CDCl3) δ 9,05 (s, 1H), 8,14 (d, J=9.8 Hz, 2H), 7,74 (m, 1H), was 7.36 (d, J=8,4 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z274 (M+).

Stage 2. The connection is produced by ka is elizaryeva the palladium arilirovaniya product of stage 1 through 4-formylphenyl-Bronevoy acid:

1H NMR (400 MHz, CDCl3) δ 10,15 (s, 1H), 9,38 (d, J=0.9 Hz, 1H), with 8.33 (d, J=8,4 Hz, 2H), 8,23 (d, J=8.5 Hz, 2H), 8,16 (d, J=0.8 Hz, 1H), 8,08 (d, J=8,8 Hz, 2H), 7,40 (d, J=8.1 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z344 (M+).

Example 31: Obtain 4-[2-(4-trifloromethyl)-pyrimidine-4-yl]-benzaldehyde

Stage 1. 4-Chloro-2-(4-trifloromethyl)-pyrimidine. Specified in the title compound is obtained by catalyzed by palladium arilirovaniya 2,4-dichloropyrimidine through 4-trifloromethyl-Bronevoy acid: melting point 70-73°C;

1H NMR (400 MHz, CDCl3) δ 8,68 (d, J=5.6 Hz, 1H), 8,16 (d, J=9.1 Hz, 2H), 7,65 (d, J=5.3 Hz, 1H), was 7.36 (DD, J=9,2, 0.9 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z274 (M+).

Stage 2. The connection is obtained by catalyzed by palladium arilirovaniya product of stage 1 through 4-formylphenyl-Bronevoy acid:

1H NMR (400 MHz, CDCl3) δ 10,13 (s, 1H), 8,91 (d, J=4,8 Hz, 1H), total of 8.74 (d, J=8.5 Hz, 2H), 8,28 (d, J=8,4 Hz, 2H), 8,03 (d, J=8,4 Hz, 2H), 7,65 (d, J=5.3 Hz, 1H), 7,39 (d, J=8.6 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z344 (M+).

Example 32: Obtain 4-[4-(4-trifloromethyl)-pyrimidine-2-yl]-benzaldehyde

Stage 1. 4-(4-Chloropyrimidine-2-yl)-benzaldehyde. The connection is produced by kata is isirimah the palladium arilirovaniya 2,4-dichloropyrimidine through 4-formylphenyl-Bronevoy acid:

1H NMR NMR (400 MHz, CDCl3) δ 10,13 (s, 1H), total of 8.74 (d, J=5.0 Hz, 1H), 8,27 (d, J=7.8 Hz, 2H), 8,04 (d, J=7.9 Hz, 2H), 7,74 (m, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z218 (M+).

Stage 2. The connection is obtained by catalyzed by palladium arilirovaniya product of Stage 1 through 4-trifloromethyl-Bronevoy acid:

1H NMR (400 MHz, CDCl3) δ 10,14 (s, 1H), 8,91 (d, J=4,2 Hz, 1H), 8,63 (d, J=8.5 Hz, 2H), of 8.37 (d, J=8,4 Hz, 2H), of 8.06 (d, J=8,8 Hz, 2H), to 7.67 (d, J=5.4 Hz, 1H), 7,35 (d, J=8.7 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z344 (M+).

Example 33: Obtain 4-[6-(4-trifloromethyl)-pyrazin-2-yl]-benzaldehyde

Stage 1. 2-Chloro-6-(4-trifloromethyl)-pyrazin. The connection is obtained by catalyzed by palladium arilirovaniya 2,6-dichloropyrazine through 4-trifloromethyl-Bronevoy acid: melting point 58-60°C;

1H NMR (400 MHz, CDCl3) δ to 8.94 (s, 1H), to 8.57 (s, 1H), 8,10 (d, J=9.0 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z274 (M+).

Stage 2. The connection is obtained by catalyzed by palladium arilirovaniya product of Stage 1 through 4-formylphenyl-Bronevoy acid:

1H NMR (400 MHz, CDCl3) δ 10,13 s, 1H), 9,07 (s, 1H), 9,03 (s, 1H), with 8.33 (d, J=8.1 Hz, 2H), 8,21 (d, J=8.7 Hz, 2H), 8,07 (d, J=7,6 Hz, 2H), 7,40 (d, J=8,3 Hz, 2H);

p> EIMS (Mass spectrometry with ionization by electron impact)m/z344 (M+).

Example 34: Obtain 4-[2-(4-trifloromethyl)-pyrimidine-5-yl]-benzaldehyde

Stage 1. 4-(2-Chloropyrimidine-5-yl)-benzaldehyde. The connection is obtained by catalyzed by palladium arilirovaniya 2,5-dichloropyrimidineby4-formylphenyl-Bronevoy acid.

Stage 2. 4-(2-Chloropyrimidine-5-yl)-benzaldehyde (to 0.92 mmol), 4-trifloromethyl-Bronevoy acid (1.10 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.01 mmol), 2M potassium carbonate solution (0,92 ml) and dioxane (5 ml) are combined in a test tube and irradiated with microwaves for 10 minutes at 150°C. the Organic layer from the reaction mixture injected directly on silicon dioxide and dryin the vacuum. Purification by chromatography on silica gel (ethyl acetate/hexane) gives the product (140 mg) as a solid white color:

1H NMR (400 MHz, CDCl3) δ 10,11 (s, 1H), 9,07 (s, 2H), to 8.57 (d, J=9.0 Hz, 2H), 8,07 (d, J=8.5 Hz, 2H), 7,82 (d, J=8,3 Hz, 2H), 7,35 (d, J=8,3 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z344 (M+).

Example 35: Obtain 4-[5-(4-trifloromethyl)-pyrimidine-2-yl]-benzaldehyde

Stage 1. 2-Chloro-5-(4-trifloromethyl)-pyrimidine. The connection is obtained by catalyzed by palladium, allerban the 2,5-dichloropyrimidine by4-trifloromethyl-Bronevoy acid.

Stage 2. 2-Chloro-5-(4-trifloromethyl)-pyrimidine (4,22 mmol), 4-formylphenyl-Bronevoy acid (5.1 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.05 mmol), 2M potassium carbonate solution (4,2 ml) and dioxane (21 ml) are combined in a test tube and irradiated with microwave for 20 minutes at 150°C. the Organic layer from the reaction mixture injected directly into silicon dioxide and dryin the vacuum. Purification by chromatography on silica gel (ethyl acetate/hexane) gives the product (75 mg) as a solid white color:

1H NMR (400 MHz, CDCl3) δ 10,13 (s, 1H), 9,06 (s, 2H), 8,68 (d, J=8,8 Hz, 2H), 8,03 (d, J=8,3 Hz, 2H), 7,68 (d, J=8,8 Hz, 2H), 7,40 (d, J=8.7 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z344 (M+).

Example 36: Obtain 4-heptafluoropropyl-6-(4-nitrophenyl)-2-(4-triptoreline)-pyrimidine

Stage 1. 4-Heptafluoropropyl-6-(4-nitrophenyl)-2-(4-triptoreline)-pyrimidine. A solution of 4-heptafluoropropyl-2-methylsulfanyl-6-(4-nitrophenyl)-pyrimidine (1.20 g, 2,90 mmol; obtained from 1-(4-nitrophenyl)-4,4,5,5,6,6,6-heptapteridae-1,3-dione in accordance with the publication of Green et al. WO 200138311 A2), 4-triptoreline-Bronevoy acid (0,608 g, 3.2 mmol), triphenylphosphine (114 mg, 0.49 mmol)and 2-thiophencarboxylic copper (II) (750 mg, 3.9 mmol) are combined in anhydrous THF (15 ml) and n is grebaut to 50°C. Then for 3 hours add three portions adduct catalyst, Tris(dibenzylideneacetone)diplegia(0), and chloroform (60 mg, cat.), and then the mixed solution is kept at 50°C during the night. Concentration and chromatography (Biotage, hexane/dichloromethane, 5:1) provide specified in the title compound (0,60 g, 40%) as a solid light yellow colour: melting point 191°C; EIMS (Mass spectrometry with ionization by electron impact)m/z514 (M+H).

Stage 2. 4-Heptafluoropropyl-6-(4-AMINOPHENYL)-2-(4-triptoreline)-pyrimidine. A solution of 4-heptafluoropropyl-2-(4-triptoreline)-6-(4-nitrophenyl)-pyrimidine (0.18 g, 0.35 mmol), iron powder (0.20 g, 3.5 mmol), ammonium sulphate, iron(II) (0.15 g, 0.3 mmol) in a mixture of ethanol/water (3:1) warm on a steam bath for 3 hours. Then it is cooled, diluted with diethyl ether (50 ml), filtered through celite Celite®, and concentrate, which gives aniline in the form of a solid yellow:

1H NMR (300 MHz, CDCl3) δ is 8.75 (d, J=8 Hz, 2H), 8,18 (d, J=8 Hz, 2H), of 7.90 (s, 1H), 7,80 (d, J=8 Hz, 2H), PC 6.82 (d, J=8 Hz, 2 H), 4,20 (s, 2H).

Example 37: Obtain 4-trifluoromethyl-6-(4-AMINOPHENYL)-2-(4-triptoreline)-pyrimidine

Stage 1. 4-Trifluoromethyl-6-(4-nitrophenyl)-2-(4-triptoreline)-pyrimidine. A solution of 4-trifluoromethyl-2-methylsulphonyl-6-(4-nitrophenyl)-pyrimidine (1.25 g, 4 mmol; obtained from 1-(4-nitrophenyl)-4,4,4-triptorelin-1,3-dione in accordance with the publication of Green et al. WO 200138311 A2), 4-triptoreline-Bronevoy acid (0.95 g, 5.0 mmol), triphenylphosphine (140 mg, of 0.60 mmol)and 2-thiophencarboxylic copper (II) (1,05 g, 5.0 mmol) are combined in anhydrous THF (25 ml) and heated to 52°C. and Then for 3 hours add three portions adduct catalyst, Tris(dibenzylideneacetone)diplegia(0), and chloroform (100 mg), and then the mixed solution is kept at 50°C for 12 hours. Concentration and chromatography (Biotage, hexane/dichloromethane, 4:1) provide specified in the title compound (0,67 g, 41%) as a solid light yellow colour: melting point 162°C;

1H NMR (300 MHz, CDCl3) δ is 8.75 (d, J=8 Hz, 2H), to 8.41 (s, 4H), 8,03 (s, 1H), 7,80 (d, J=8 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z414 (M+H).

Stage 2. 4-Trifluoromethyl-6-(4-AMINOPHENYL)-2-(4-triptoreline)-pyrimidine. A solution of 4-trifluoromethyl-2-(4-triptoreline)-6-(4-nitrophenyl)-pyrimidine (0.50 g, 1.2 mmol), iron powder (0.50 g, 9 mmol), ammonium sulphate, iron(II) (0.5 g, 1.0 mmol) in a mixture(3:1) ethanol/water (30 ml) by warming on the steam bath for 3 hours. Then it is cooled, diluted with diethyl ether (50 ml), filtered through celite Celite®, and concentrate. The crude amine purified on Biotage column (hexane/ethyl acetate/dichloromethane, 4:1:1), th is gives pure aniline (0,22 g). This substance is used directly in the formation of the corresponding carbamate:

1H NMR (300 MHz, CDCl3) δ is 8.75 (d, J=8 Hz, 2H), 8,16 (d, J=8 Hz, 2H), 7,81 (s, 1H), to 7.77 (d, J=8 Hz, 2H), PC 6.82 (d, J=8 Hz, 2H), 4,15 (s, 2H).

Example 38: Obtain 4-[2-(4-triptoreline)-pyrimidine-4-yl]-phenylamine

Stage 1. 4-(4-Nitrophenyl)-2-(4-triptoreline)-pyrimidine. The metal sodium (82,7 mg of 3.60 mmol), dissolved in absolute ethanol (3 ml) is added dehydrate 4-triftorperasin-hydrochloride (938 mg, of 3.60 mmol), then add ethanol (4 ml). After 30 minutes, add 3-dimethylamino-1-(4-nitrophenyl)-propane (498 mg, and 2.26 mmol)and the mixture heated to boiling under reflux for approximately 66 hours, and then allowed to cool. The mixture is concentrated to obtain a solid reddish-brown color, which is ground to powder with a saturated solution of sodium bicarbonate. The solid is collected and dried in air, giving 937 mg Then dissolved in a mixture of chloroform/ethyl acetate and passed through silica gel with elution with a mixture of chloroform/ethyl acetate, giving specified in the title compound (710 mg, 91%): melting point 175-176,5°C;

1H NMR δ 9,01 (d, J=5.3 Hz, 1H), 8,73 (d, J=8,2 Hz, 2H), 8,43 (s, 4H), of 7.82 (d, J=8.1 Hz, 2H), 7,76 (d, J=5,2 Hz, 1H);

EIMS (Mass spectrometry with what onsala electron impact) m/z345 (M+, 100), 299 (57). Analysis: Calculated for C17H10F3N3O2: C $ 59.13 USD; H, 2,92; N, 12,17. Found: C, 58,82; N, 2,63; N, 11,98.

Stage 2. 4-[2-(4-Triptoreline)-pyrimidine-4-yl]-phenylamine. A mixture of 4-(4-nitrophenyl)-2-(4-trifluoromethyl-phenyl)-pyrimidine (670 mg, 1.94 mmol) and 10% palladium catalyst on a carbon carrier (Pd/C) (75 mg) in ethanol (30 ml) was placed on a Parr shaker under hydrogen pressure of 40 pounds per square inch at room temperature. After 7 hours the mixture is filtered through celite Celite®, and remove ethyl alcoholin the vacuum. The residue is distributed between ethyl acetate and a saturated solution of NaHCO3and the organic phase is dried (MgSO4). Concentration gives a solid which is dissolved in ethyl acetate and filtered through a plug of silica gel. Concentration gives specified in the title compound (500 mg, 82%): melting point 166-167°C;

1H NMR δ is 8.75 (d, J=and 5.30 Hz, 1H), 8,67 (d, J=8,3 Hz, 2H), 8,10 (d, J=8,9 Hz, 2H), of 7.75 (d, J=7.9 Hz, 2H), 7,54 (d, J=5.3 Hz, 1H), 6,80 (d, J=8.6 Hz, 2H), 4,03 (Shir.s, 2H);

MS (API-ES+) (Mass spectrometry with chemical ionization at atmospheric pressure and ionization elektrorazpredelenie) 316 (M+H)+, 100). Analysis: Calculated for C17H12F3N3: C, 64,76; H, A-3.84; N, 13,33. Found: C, 64,37; N, 3,71; N, 13,08.

Example 39: Obtain 2-chloro-4-[3-(4-triptoreline)-[1,2,4]triazole-1-yl]-Fenelon is on

Stage 1. 1-(3-Chloro-4-nitrophenyl)-3-(4-trifluoromethyl-phenyl)-1N-[1,2,4]triazole. A solution of NBS (180 mg, 1 mmol) in dichloromethane (4 ml) is stirred under nitrogen atmosphere at 0°C, and at the same time, the syringe add dimethyldisulfide (110 mg, 1.8 mmol). The solution, which takes the form of a solid white color, then cooled to -20°C, and add (N-(3-chloro-4-nitrophenyl)-N'-(4-trifluoromethyl-benzylidene)-hydrazine (200 mg, of 0.58 mmol) in dichloromethane (4 ml). The solution is allowed to warm to ambient temperature and stirred for additional 2 hours. Then the resulting orange solution was diluted with dichloromethane (25 ml) and washed with water and brine before drying and concentrating. The resulting orange solid hydrazone-bromide (150 mg) is then treated directly by tetrazolium (25 mg, 0.35 mmol) and triethylamine (50 μl, 0.35 mmol) in absolute ethanol (5 ml). The resulting solution is orange-brown color warm while boiling under reflux for 2 hours. Analysis by thin layer chromatography (TLC) shows that the initial bromide is first converted into two intermediate yellow, which then disappear and are replaced by a single, colorless spot. The solution is orange then rasb the keys water (10 ml), obtaining solid reddish-brown-yellow color, which is filtered, air-dried, and recrystallized from toluene, giving a solid yellow-reddish-brown (60 mg): melting point 185°C;

1H NMR (300 MHz, CDCl3) δ at 8.60 (s, 1H), to 8.41 (d, J=8.7 Hz, 1H), with 8.33 (d, J=7.5 Hz, 2H), of 7.90 (d, J=2 Hz, 1H), of 7.70 (d, J=7.5 Hz, 2H), 7,65 (DD, J=8,7, 2 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z368,9. Analysis: Calculated for C15H8ClF3N4O2: C, 48,86; H, 2,19; N, 15,20. Found: C, 48,39; N, 2,61; N, 14,91.

Stage 2. 2-Chloro-4-[3-(4-triptoreline)-[1,2,4]triazole-1-yl]-phenylamine. The solution nitroaniline derived (0.75 g, 2.0 mmol) in methyl alcohol (7 ml) and water (3 ml) is treated with iron powder (0.7 g, 12.5 mmol) and ammonium sulfate iron(III) (uranyl; 0.7 g, 1.8 mmol). The solution is heated on the steam bath for 3 hours, after which analysis by thin layer chromatography indicates complete transformation into more polar, fluorescent product. The solution is cooled and filtered, and the filtrate concentratedin the vacuum. Purification by chromatography using a short tube of silica gel (hexane/ethyl acetate/dichloromethane, 7:2:1) gives the amine (0.55 g) as a solid light-reddish-brown colour: melting point 148°C;

1H NMR (300 MHz, CDCl3) δ of 8.40 (s, 1H), 8,31 (d, J=8,4 Hz, 1H), 7,72 (d, J=8,4 Hz, 2H), 7,69 (d, J=2 Hz, 1H), 7,42 (DD, J=8,5, 2 Hz, 1H), 6,9 (d, J=8,4 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z340,4, 342,3 (M+H). Analysis: Calculated for C15H10ClF3N4: C, 53,19; H, 2,98; N, EQUAL TO 16.83. Found: C, 52,90; N, 3,10; N, Equal To 16.83.

Example 40: Obtain 4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenylamine

Stage 1. 1-(4-Trifloromethyl)-3-(4-nitrophenyl)-1N-[1,2,4]triazole. A solution of NBS (0,70 g, 3.9 mmol) in dichloromethane (25 ml) is stirred under nitrogen atmosphere at 0°C, and at the same time, the syringe add dimethyldisulfide (0.40 g, 6.5 mmol). The solution, which takes the form of a solid white color, then cooled to -20°C, and addN-(4-nitrobenzylidene)-N'-(4-trifloromethyl)-hydrazine (0,70 g of 2.15 mmol) in dichloromethane (10 ml). The solution is allowed to warm to ambient temperature and stirred for additional 2 hours. Then the resulting orange solution was diluted with dichloromethane (25 ml) and washed with water and brine before drying and concentrating. The resulting orange solid hydrazone-bromide (0.9 g) is then treated directly by tetrazolium (154 mg, 2.2 mmol) and triethylamine (280 μl, 0.23 mmol) in absolute ethanol (5 ml). The resulting solution is orange-brown CEE is as warm boiling under reflux for 2 hours. Analysis by thin layer chromatography (TLC) indicates that the source of bromide is first converted into two intermediate yellow, which are substituted with one, colorless spot. The orange solution is then concentrated and purified by chromatography (hexane/ethyl acetate/dichloromethane, 2:1:2), with the specified title compound (0,30 g) as a solid light yellow colour: melting point 147°C;

1H NMR (300 MHz, CDCl3) δ 8,68 (s, 1H), 8,40 (d, J=5 Hz, 2H), 8,35 (d, J=5 Hz, 2H), a 7.85 (d, J=8 Hz, 2H), 7,42 (d, J=8 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z350 (M+, 100), 299 (57).

Stage 2. 4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenylamine. Catalytic reduction using a palladium catalyst on a carbon carrier (Pd/C) in ethanol in an atmosphere of hydrogen to give the corresponding aniline in the form of a solid light gray: melting point 160°C;

1H NMR (300 MHz, CDCl3) δ and 8.50 (s, 1H), 8,00 (d, J=8,4 Hz, 2H), 7,78 (d, J=8.7 Hz, 2H), 7,35 (d, J=8 Hz, 2H), 6,76 (d, J=8.7 Hz, 2H), 3,9 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z321.

Example 41: Obtain 4-[1-(4-pentafluorophenyl)-1N-[1,2,4]triazole-3-yl]-phenylamine

Stage 1. 1-(4-Pentafluorophenyl)-3-(4-nitrophenyl)-1N[1,2,4]triazole. A suspension of 3-(4-nitrophenyl)triazole (11.4 g, 60 mmol), 1-iodine-4-pentafluorobenzoyl (20 g, 60 mmol), cesium carbonate (39,0 g, 120 mmol), CuI (3.5 g, 18 mmol), 8-hydroxyquinoline solution (2.0 g, of 13.8 mmol) and a mixture of DMF-H2O (9:1, 155 ml) and heat at 150°C for 5 hours and then cooled. The contents of the round bottom flask was poured into water (150 ml) and extracted with diethyl ether (2×100 ml). The organic layer is dried and concentrated, and the solid residue is recrystallized from methyl alcohol and water, which gives nitrotriazole (11.8 g, 49%) as a solid reddish-brown: the melting temperature of 170-175°C;

1H NMR (300 MHz, CDCl3) δ 8,68 (s, 1H), 8,40 (d, J=5 Hz, 2H), 8,35 (d, J=5 Hz, 2H), a 7.85 (d, J=8 Hz, 2H), 7,42 (d, J=5,2 Hz, 8 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z400 (M+).

Stage 2. 4-[1-(4-Pentafluorophenyl)-1N-[1,2,4]triazole-3-yl]-phenylamine. Catalytic reduction using a palladium catalyst on a carbon carrier (Pd/C) in ethanol in an atmosphere of hydrogen to give the corresponding aniline in the form of a solid light-reddish-brown colour: melting point 160°C;

1H NMR (300 MHz, CDCl3) δ 8,55 (s, 1H), 8,00 (d, J=1 Hz, 2H), 7,78 (d, J=8 Hz, 2H), 7,35 (d, J=8 Hz, 2H), 6,78 (d, J=8 Hz, 2H), 3,9 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z371.

Example 42: Obtain 4-[1-(4-gepruft profilometer)-1 N-[1,2,4]triazole-3-yl]-phenylamine

Stage 1. 1-(4-Heptachlorobiphenyl)-3-(4-nitrophenyl)-1N-[1,2,4]triazole. A suspension of 3-(4-nitrophenyl)triazole (1.0 g, 5.2 mmol), 1-iodine-4-heptachlorodibenzo (6,1 g, 15.8 mmol), cesium carbonate (10.0 g, 30.7 mmol), CuI (900 mg, 4.7 mmol)and 8-hydroxyquinoline solution (500 mg, 3.4 mmol) in a mixture of DMF-H2O (9:1, 40 ml) and heat at 150°C for 12 hours, then cooled, and the contents of the round bottom flask was poured into water (50 ml) and concentrated solution of NH4OH (50 ml). The blue solution is extracted with diethyl ether (100 ml)and the organic layer is separated and filtered to remove some portion of insoluble matter, then dried and concentrated to dryness. The solid residue is recrystallized from a mixture of methyl alcohol/water, providing nitrophenyl-triazole (4,69 g) as a solid light-reddish-brown colour: melting point 114-116°C;

1H NMR (300 MHz, CDCl3) δ 8,66 (s, 1H), 8,40 (m, 4H), a 7.85 (d, J=8 Hz, 2H), 7,42 (d, J=8 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/zof 450.1 (M+).

Stage 2. 4-[1-(4-Heptachlorobiphenyl)-1N-[1,2,4]triazole-3-yl]-phenylamine. Catalytic reduction under the conditions described above, gives the corresponding aniline in the form of a solid light-reddish-brown: temperature PL is the exercise 181-183°C;

1H NMR (300 MHz, CDCl3) δ 8,54 (s, 1H), 8,00 (d, J=8 Hz, 2H), 7,80 (d, J=8 Hz, 2H), 7,40 (d, J=8 Hz, 2H), 6,78 (d, J=8 Hz, 2H), 3,9 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z421,3 (M+1).

Example 43: Obtain 4-[4-(4-triptoreline)-imidazol-1-yl]-phenylamine

Stage 1. 4-[4-(4-Triptoreline)-1N-imidazol-1-yl]-nitrobenzene. 4-Triptoreline-imidazole (1,43 g, 6.7 mmol), 4-fluoro-nitrobenzene (1.2 g, 8.5 mmol) and potassium carbonate (1.5 g, 10.9 mmol) are combined in dimethylformamide (15 ml) and heat at 100°C for 6 hours. The cooled solution is then poured onto water (100 ml)and the resulting solid is filtered off and dried in air, giving specified in the title of the imidazole (1.0 g) as a solid light yellow colour: melting point 197°C. Analysis: Calculated for C16H10F3N3O2: C, 57,66; H, TO 3.02; N, 12,61. Found: C, 57,69; N, A 3.01; N, 12,48.

Stage 2. 4-[4-(4-Triptoreline)-imidazol-1-yl]-phenylamine. Catalytic reduction using a palladium catalyst on a carbon carrier (Pd/C) in ethanol in an atmosphere of hydrogen to give the corresponding aniline in the form of a solid light gray: melting point 142-143°C;

1H NMR (400 MHz, CDCl3) δ of 7.90 (d, J=1 Hz, 2H), of 7.75 (s, 1H), 7,65 (d, J=1 Hz, 2H), 7,52 (s, 1H), 7,19 (d, J=8 Hz, 2H), 6.75 in (l, 8 is C, 2H), 3,8 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z302,0.

Example 44: Obtain 4-[1-(4-triptoreline)-1N-imidazol-4-yl]-phenylamine

Stage 1. 4-[4-(4-Triptoreline)-1N-imidazol-1-yl]-nitrobenzene. Get the same as in stage 1 of the previous example.

Stage 2. 4-[1-(4-Triptoreline)-1N-imidazol-4-yl]-phenylamine. Catalytic reduction using a palladium catalyst on a carbon carrier (Pd/C) in ethanol in an atmosphere of hydrogen to give the corresponding aniline in the form of a solid light gray: melting point 191°C;

1H NMR (400 MHz, CDCl3) δ a 7.92 (s, 1H), 7,76 (d, J=8 Hz, 2H), 7,66 (d, J=4.5 Hz, 2H), 7,55 (s, 1H), 6.75 in (d, J=4.5 Hz, 2H), 3,8 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z304,0. Analysis: Calculated for C16H12F3N3: C, 63,36; H, 3,99; N, 13,85. Found: C, 63,14; N, 4,07; N, 13,52.

Example 45. Getting 4-[1-(4-trifloromethyl)-1N-imidazol-4-yl]-phenylamine

Stage 1. 4-(4-Nitrophenyl)-1-[4-trifloromethyl)-1N-imidazole. The conditions described in the publication: Porretta et al.Farmaco, Edizione Scientifica1985, 40, 404, is used to convert 4-triphtalocyaninine (5.3 g, 30 mmol) and α-bromo-4-nitroacetophenone (3.7 g, 15 mmol) imidazole (2.1 g, 41%).

Stud is I 2. 4-[1-(4-Trifloromethyl)-1N-imidazol-4-yl]-phenylamine. Catalytic reduction using a palladium catalyst on a carbon carrier (Pd/C) in ethanol in an atmosphere of hydrogen to give the corresponding aniline in the form of a solid light gray: melting point 167°C;

1H NMR (300 MHz, CDCl3) δ 7,83 (s, 1H), to 7.64 (d, J=4,8 Hz, 2H), 7,47 (d, J=4.4 Hz, 2H), 7,40 (s, 1H), was 7.36 (d, J=4,8 Hz, 2H), 6.75 in (d, J=4.4 Hz, 2H), 3,5 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z320. Analysis: Calculated for C16H12F3N3O: C, 60,19; H, WITH 3.79; N, 13,16. Found: C, 59,91; N, To 3.67; N, 13,03.

Example 46. Getting 4-(4-AMINOPHENYL)-2-[4-trifloromethyl)-2,4-dihydro-[1,2,4]triazole-3-one

Stage 1. 4-(4-Nitrophenyl)-2-(4-trifloromethyl)-2,4-dihydro-[1,2,4]triazole-3-one. Specified in the title compound receive in accordance with the method of publication: Henbach, DE 2724891 A1, 1978, with modifications relating to the carrying out in three stages: In addition to aniline, 4-nitroaniline is used instead of 3,5-dichloraniline, and dehydrated THF is used as solvent instead of toluene. In education triazolinones rings, use triphosgene (0,65 EQ.) instead of phosgene: melting point 136-140°C;

1H NMR (300 MHz, CDCl3) δ of 8.40 (d, J=8,8 Hz, 2H), with 8.05 (d, J=8,8 Hz, 2H), to 7.99 (s, 1H), 7,89 (d, J=9,3 Hz, 2H), 7,32 (d, J=9,3 is C, 2H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z367 (M+H).

Stage 2. 4-(4-AMINOPHENYL)-2-(4-trifloromethyl)-2,4-dihydro-[1,2,4]triazole-3-one. Nitrophenyl-triazolinone (0.037 g, 0.10 mmol) was dissolved in absolute ethanol (1 ml) under nitrogen atmosphere. To this add the chloride dihydrate tin(II) (0,114 g, 0.51 mmol)and the mixture is stirred at the boil under reflux for 2 hours. The mixture is cooled to 25°C., poured into a mixture of ice-H2O (25 ml)and the aqueous mixture was adjusted to pH 9-10 by 1N NaOH solution. The mixture is extracted with diethyl ether (3×25 ml)and the combined organic extracts dried (MgSO4), filtered and concentrated to dryness, giving a solid dark brown color (0,0297 g, 87%), which is used without further purification: the melting temperature of 115-120°C;

1H NMR (300 MHz, CDCl3) δ 8,07 (d, J=9.7 Hz, 2H), 7,73 (s, 1H), 7,32-of 7.23 (m, 4H), 6,77 (d, J=8.5 Hz, 2H), 3,85 (width, 2H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z336 (M+).

Example 47: Obtain 4-[5-(4-triptoreline)-4,5-dihydro-isoxazol-3-yl]-phenylamine

Stage 1.Tert-butyl ester {4-[5-(4-triptoreline)-4,5-dihydro-isoxazol-3-yl]-phenyl}-carbamino acid. To a stirred solution of NCS (57 mg, 0,424 mmol) and pyridine (3 ml) in chloroform (1.7 ml) hydroxy add the 4- N-tert-butoxycarbonyl-aminobenzaldehyde (100 mg, 0,424 mmol). The reaction mixture was stirred at room temperature for 10 minutes. Then add 4-trifloromethyl (78 μl, of 0.53 mmol), and the temperature was raised to 45°C. To this solution is added dropwise a triethylamine (62 μl, 0,445 mmol)dissolved in chloroform (0.5 ml). The reaction mixture was stirred at 45°C for 5 hours. The cooled solution was diluted with chloroform (10 ml) and washed with water (2×5 ml). The organic phase is then dried over MgSO4, filtered and concentrated, giving isoxazole (100 mg, 58%):

1H NMR (400 MHz, CDCl3) δ 7,40-7,83 (m, 8H), 6,60 (Shir.s, 1H), USD 5.76 (DD, J=11,0, 7.7 Hz, 1H), 3,81 (DD, J=16.5, and of 11.0 Hz, 1H), 3,29 (DD, J=16.5, and 7.7 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z406 (M+).

Stage 2. 4-[5-(4-Triptoreline)-4,5-dihydro-isoxazol-3-yl]-phenylamine. To a stirred solutionNbutoxycarbonyl-isoxazoline (obtained in stage 1) in dichloromethane (2.5 ml) is added triperoxonane acid (6,16 ml)and the reaction mixture stirred at room temperature for 3 hours. The solution is concentrated, and the residue washed with saturated solution of KHCO3(5 ml) and stirred for 30 minutes. The mixture is then extracted with dichloromethane (3×10 ml). The organic phase is dried over MgSO4filter and concentrate to provide a preference for aguinaga aniline (68 mg, 90%):

1H NMR (400 MHz, CDCl3) δ 7,45-7,63 (m, 6H), to 6.67 (d, J=8.6 Hz, 2H), 5,72 (DD, J=10,9, and 7.6 Hz, 1H), 3,92 (Shir.s, 2H), 3,78 (DD, J=16,7, up 10.9 Hz, 1H), 3,25 (DD, J=16,7, 7,6 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z306 (M+).

Example 48: Obtain 4-[3-(4-trifloromethyl)-4,5-dihydro-isoxazol-5-yl]-phenylamine

To a stirred solution of NCS (85 μl, 0,634 mmol) and pyridine (4 ml) in chloroform (2.5 ml) is added to the oximepair-triphtalocyaninine (130 mg, 0,634 mmol). The reaction mixture is warm at 50°C for 3 hours. Then add 4-aminosterol (93 μl, 0,793 mmol), then added dropwise a solution of triethylamine (93 μl, 0,666 mmol)dissolved in chloroform (0.5 ml). The reaction mixture was stirred at 50°C for 3 hours. The cooled solution was diluted with chloroform (15 ml) and washed with water (2×10 ml). Then the organic phase is dried over MgSO4filter and concentrate. The residue is purified by radial chromatography using a solution of hexane/ethyl acetate (2:1) as eluent (Rf=0,18) with 4-[3-(4-trifloromethyl)-4,5-dihydro-isoxazol-5-yl]-phenylamine (125 mg; 61%):

1H NMR (400 MHz, CDCl3) δ 7,73 (d, J=8,2 Hz, 2H), 7,25 (d, J=8,2 Hz, 2H), 7,17 (d, J=8,2 Hz, 2H), of 6.68 (d, J=8,2 Hz, 2H), 5,65 (DD, J=10,9, and 8.9 Hz, 1H), 3,55-3,75 (Shir.s, 2H), to 3.67 (DD, J=16,8, up 10.9 Hz, 1H), 3,30 (DD, J=16,8, a 8.9 Hz, 1H);

EIMS (Mass spectrometer is I with ionization by electron impact) m/z322 (M+).

Example 49: Obtain 1-(4-AMINOPHENYL)-3-(4-trifloromethyl)-1,3-dihydroimidazole-2-it

These connections receive in accordance with the method described in the publication: Bromidge et al. WO 2003057220 A1, with minor modifications.

Stage 1. (2.2-Dimethoxymethyl)-(4-trifloromethyl)amine. To a stirred solution of 4-triphtalocyaninine (1 ml, 7,46 mmol) and dimethylacetal of glyoxalase (60% (volume/volume) in water; of 8.95 mmol, 1.6 ml) in ethanol (37 ml) is added 10% palladium catalyst on a carbon carrier (Pd/C (300 mg). The mixture is vacuum and rinsed with nitrogen three times. Then in the device in the form of a cylinder injected hydrogen, and the mixture is stirred under hydrogen pressure of 1 atmosphere for 31 hours. The mixture is filtered through a layer of celite Celite®, and the layer was washed with ethanol (25 ml). The ethanol is removed under reduced pressure, and the residue was diluted with dichloromethane (30 ml). The layers separated, and the organic phase is dried over MgSO4filter and concentrate, which gives (2.2-dimethoxymethyl)-(4-trifloromethyl)amine (1.7 g, 86%):

1H NMR (400 MHz, CDCl3) δ? 7.04 baby mortality (d, J=8,9 Hz, 2H), 6,59 (d, J=8,9 Hz, 2H), 4,56 (t, J=5.4 Hz, 1H), 3,92 (Shir.s, 1H), 3,51 (d, J=5.4 Hz, 2H), 3,42 (s, 6H);

EIMS (Mass spectrometry with ionization by electron impact)m/z265 (M+).

Stage 2. 1-(2,2-Dimethoxymethyl)-3-(4-nitrophenyl)-1-(4-triptoreline the Nile)-urea. To a stirred solution of (2,2-dimethoxymethyl)-(4-trifloromethyl)amine (0,85 g, 3.2 mmol)dissolved in dichloromethane (32 ml), addpair-nitrophenyl-isocyanate (0,58 g of 3.53 mmol)and the reaction mixture stirred at room temperature overnight. The mixture is diluted with dichloromethane (50 ml) and washed successively with a solution of NaHCO3(30 ml) and brine (30 ml). Then the organic phase is dried over MgSO4filter and concentrate. The residue is purified via radial chromatography using a solution of hexane/ethyl acetate (2:1) as eluent (Rf=0,32) to provide 1-(2,2-dimethoxymethyl)-3-(4-nitrophenyl)-1-(4-trifloromethyl)-urea (0.87 g, 63%):

1H NMR (400 MHz, CDCl3) δ of 8.15 (d, J=9,2 Hz, 2H), 7,50-7,30 (m, 6H), 7,02 (Shir.s, 1H)and 4.65 (t, J=5.4 Hz, 1H), 3,82 (d, J=5.4 Hz, 2H), 3,41 (s, 6H);

EIMS (Mass spectrometry with ionization by electron impact)m/z429 (M+).

Stage 3. 1-(4-Nitrophenyl)-3-(4-trifloromethyl)-1,3-dihydroimidazole-2-it. To a stirred solution of 1-(2,2-dimethoxymethyl)-3-(4-nitrophenyl)-1-(4-trifloromethyl)-urea (0,23 g of 0.53 mmol)dissolved in toluene (28 ml), add concentrated hydrochloric acid (2 drops). The reaction mixture is stirred at the boil under reflux for 3 hours. The cooled solution is diluted with ethyl acetate (75 ml) and washed with saturated dissolve the om NaHCO 3(25 ml) and brine (25 ml). Then the organic phase is dried over MgSO4filter and concentrate. The residue is purified via radial chromatography using a solution of hexane/ethyl acetate (2:1) as eluent (Rf=0,28) to provide 1-(4-nitrophenyl)-3-(4-trifloromethyl)-1,3-dihydroimidazole-2-she (134 mg, 71%):

1H NMR (400 MHz, CDCl3) δ 8,35 (d, J=9,2 Hz, 2H), to 7.93 (d, J=9,2 Hz, 2H), to 7.67 (d, J=9,2 Hz, 2H), 7,34 (d, J=9,2 Hz, 2H), 6.87 in (d, J=3.3 Hz, 1H), for 6.81 (d, J=3.3 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z365 (M+).

Stage 4. 1-(4-AMINOPHENYL)-3-(4-trifloromethyl)-1,3-dihydro-imidazol-2-it. To a stirred solution of 1-(4-nitrophenyl)-3-(4-trifloromethyl)-1,3-dihydroimidazole-2-she (120 mg, 0.33 mmol) in ethyl acetate (3.5 ml) is added tin dichloride (371 mg, of 1.64 mmol)and the reaction mixture is stirred at the boil under reflux for 3 hours. The cooled solution was poured on ice (15 ml)and the pH adjusted to bring to pH 7-8 by adding a 10%solution of NaHCO3. The mixture is extracted with ethyl acetate (3×10 ml) and washed with brine (10 ml). Then the organic phase is dried over MgSO4, filtered and concentrated to obtain 1-(4-AMINOPHENYL)-3-(4-trifloromethyl)-1,3-dihydroimidazole-2-she (102 mg, 92%):

1H NMR(400 MHz, CDCl3) δ 7,72 (d, J=8,8 Hz, 2H), 7,37 (d, J=8,8 Hz, 2H), 7,32 (d, J=8.8 G is, 2H), 6,76 (d, J=8,8 Hz, 2H), 6,69 (d, J=3.3 Hz, 1H), 6,65 (d, J=3.3 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z335 (M+).

Example 50: Obtain 1-(4-AMINOPHENYL)-3-(4-trifloromethyl)-imidazolidin-2-it

To a solution of 1-(4-nitrophenyl)-3-(4-trifloromethyl)-1,3-dihydroimidazole-2-she (144 mg, 0,395 mmol) in ethanol (40 ml) is added 10%palladium catalyst on a carbon carrier (Pd/C, 100 mg). The mixture is vacuum and rinsed with nitrogen three times. In the vessel Parra create a hydrogen pressure of 45 psi and shaken for 5 hours. After reducing the pressure in the vessel solution is filtered through a layer of celite Celite®, and the layer was washed with ethanol (25 ml). The ethanol is removed under reduced pressure with the provision specified in the title of the product (114 mg, 95%):

1H NMR (400 MHz, CDCl3) δ to 7.61 (d, J=9,2 Hz, 2H), 7,33 (d, J=9,2 Hz, 2H), 7,21 (d, J=8.6 Hz, 2H), of 6.71 (d, J=9,2 Hz, 2H), 3,92 (s, 4H), 3,61 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z307 (M+).

Example 51: Obtain 4-[6-(4-trifloromethyl)-pyridazin-3-yl]-phenylamine

Stage 1. 3-Chloro-6-(4-trifloromethyl)-pyridazin. To a solution containing 3,6-dichloropyridazin (0.3 g, a 2.01 mmol), 4-trifloromethyl-Bronevoy acid (0.50 g, 2,42 mmol) and 2 M K2CO3(2 ml, a 4.03 mmol), the solution is installed in anhydrous 1,4-dioxane (11 ml), add dichlorobis(triphenylphosphine)palladium(II) (14 mg, 0.02 mmol). The mixture is subjected to microwave irradiation using Discover firms CEM at 190°C for 30 minutes. The mixture is diluted with diethyl ether (100 ml) and washed with brine (30 ml). Then the organic phase is dried over MgSO4filter and concentrate. The residue is purified via radial chromatography using a solution of hexane/ethyl acetate (3:1) as eluent. There are two factions. The first fraction (Rf=0,63), as has been shown, is the product of a double Suzuki reaction (95 mg, 12%). Selected second fraction (Rf=0,34) identify as 3-chloro-6-(4-trifloromethyl)-pyridazin (174 mg, 32%):

1H NMR (400 MHz, CDCl3) δ 8,10 (d, J=9,2 Hz, 2H), 7,83 (d, J=8,9 Hz, 2H), 7,60 (d, J=8,9 Hz, 2H), 7,37 (d, J=9,2 Hz, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z274 (M+).

Stage 2. 4-[6-(4-Trifloromethyl)-pyridazin-3-yl]-phenylamine. To a solution containing 3-chloro-6-(4-trifloromethyl)-pyridazin (157 mg, or 0.57 mmol), 4-aminophenylarsonic acid (118 mg, 0.86 mmol) and 2 M2CO3(or 0.57 ml, to 1.14 mmol)dissolved in anhydrous 1,4-dioxane (3.5 ml), add dichlorobis(triphenylphosphine)palladium(II) (4 mg, 0,006 mmol). The mixture is subjected to microwave irradiation using Discover firms CEM at 190°C for 30 minutes. A mixture of razbam Aut diethyl ether (100 ml) and washed with brine (30 ml). Then the organic phase is dried over MgSO4filter and concentrate. The residue is purified via radial chromatography using a solution trichlormethane/methyl alcohol (97:3) as eluent (Rf= 0,26) with the provision specified in the title compound (105 mg, 56%):

1H NMR (400 MHz, CDCl3) δ 8,18 (d, J=8.6 Hz, 2H), 8,01 (d, J=8.6 Hz, 2H), 7,30 was 7.45 (m, 4H), PC 6.82 (d, J=8.6 Hz, 2H), 3.96 points (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z331 (M+).

Example 52: Obtain 4-[3-(4-trifloromethyl)-4,5-dihydro-[1,2,4]oxadiazol-5-yl]-benzaldehyde

Connection receive in accordance with the General method of publication: Srivastava et al.J. Heterocycl. Chem. 1987, 24, 101, with minor modifications. To a stirred solution of 4-(triptoreline)benzamidoxime (Acros) (300 mg, about 1.36 mmol), dissolved in acetic acid (1.4 ml), add 1,4-terephthalaldehyde (1.1 g, 8,18 mmol)and the reaction mixture was stirred at room temperature for 4 days. The mixture is then dissolved in trichloromethane (20 ml) followed by addition of heptane (10 ml). This solution is concentrated under reduced pressure. This technique is performed again, twice. The residue is purified via radial chromatography using a solution trichlormethane/methyl alcohol (99:1) as eluent. delayt two factions. The first selected fraction (Rf=0,30), as has been shown, is the starting material (20 mg). The second selected fraction (Rf=0,17), as shown, is indicated in the title compound (23 mg, 5%):

1H NMR (400 MHz, CDCl3) δ 10,02 (s, 1H), to $ 7.91 (d, J=8,2 Hz, 2H), to 7.77 (d, J=9,2 Hz, 2H), of 7.70 (d, J=8,2 Hz, 2H), 7,27 (d, J=8,2 Hz, 2H), only 6.64 (d, J=4.3 Hz, 1H), 5,18 (d, J=4.3 Hz, 1H);

EIMS (Mass spectrometry with ionization by electron impact)m/z336 (M+).

Example 53: Obtain 4-[5-(4-trifloromethyl)-[1,2,4]oxadiazol-3-yl]-phenylamine

Stage 1.Tert-butyl ester {4-[5-(4-trifloromethyl)-[1,2,4]oxadiazol-3-yl]-phenyl}-carbamino acid. To a stirred solution of tert-butyl 4-(N-hydroxycarbamoyl)-phenylcarbamate (Ace Synthesis) (500 mg, 1,99 mmol)dissolved in acetic acid (2.5 ml), add 4-triphtalocyaninine (1.7 ml, 11,94 mmol)and the reaction mixture was stirred at room temperature for 4 days. The mixture is diluted with trichloromethane (20 ml) and filtered through a layer of celite Celite®. This layer washed with trichloromethane (20 ml). Then to the solution was added heptane (20 ml)and the solution concentrated under reduced pressure. This technique was repeated twice. The residue is purified via radial chromatography using a solution of hexane/ethyl acetate, alcohol (3:1) as eluent. delayt two factions. The first selected fraction (Rf=0,42), as shown, is indicated in the title compound (127 mg, 15%):

1H NMR (300 MHz, CDCl3) δ compared to 8.26 (d, J=8,9 Hz, 2H), of 8.09 (d, J=8,9 Hz, 2H), 7,52 (d, J=8.6 Hz, 2H), 7,39 (d, J=8,3 Hz, 2H), 6,70 (s, 1H), and 1.54 (s, 9H);

EIMS (Mass spectrometry with ionization by electron impact)m/z421 (M+).

The second selected fraction (Rf=0,11), as shown, includes 4,5-dihydro-1,2,4-oxadiazol (96 mg, 11%):

1H NMR (300 MHz, CDCl3) δ of 8.40 (d, J=8,9 Hz, 2H), 8,00 (d, J=8,9 Hz, 2H), 7,51 (d, J=8,9 Hz, 2H), 7,22-7,31 (m, 3H), 6.87 in (s, 1H), and 1.54 (s, 9H);

EIMS (Mass spectrometry with ionization by electron impact)m/z423 (M+).

Stage 2. 4-[5-(4-Trifloromethyl)-[1,2,4]oxadiazol-3-yl]-phenylamine. To a stirred solutiontert-butyl ether complex {4-[5-(4-Trifloromethyl)-[1,2,4]oxadiazol-3-yl]-phenyl}-carbamino acid (198 mg, 0.47 mmol) in dichloromethane (4,7 ml) add triperoxonane acid (11,76 mmol, of 0.87 ml)and the reaction mixture stirred at room temperature for 3 hours. The solution is concentrated, and the residue washed with saturated solution of KHCO3(10 ml) and stirred for 30 minutes. The mixture is then extracted with dichloromethane (3×10 ml). The organic phase is dried over MgSO4, filtered and concentrated to provide 4-[5-(4-trifloromethyl)-[1,2,4]oxadiazol-3-yl]-phenylamine (127 mg; 84%):

1H NMR (300 M is C, CDCl3) δ compared to 8.26 (d, J=8,9 Hz, 2H), of 7.97 (d, J=8,9 Hz, 2H), 7,39 (d, J=8.6 Hz, 2H), 6,77 (d, J=8.6 Hz, 2H), 3,40-3,80 (Shir.s, 2H);

EIMS (Mass spectrometry with ionization by electron impact)m/z321 (M+).

Example 54: Obtain 1-(4-AMINOPHENYL)-4-(4-trifloromethyl)-piperazine-2,5-dione

Stage 1. Methyl ester of 4-nitrophenylamino-acetic acid. To a solution of ethyl-bromoacetate (60 g, 0.36 mol) and 4-nitroaniline (5 g, being 0.036 mol) in dimethylformamide (100 ml) is added NaHCO3(60 g, 0.71 mol) and potassium iodideTetra-nbutylamine (500 mg, cat.). The solution is heated to 90°C for 16 hours, and then cooled and poured into water (300 ml). The resulting solid yellow filtered and dried in air. Recrystallization from methanol gives methyl ester (5 g) as a solid light yellow colour: melting point 179-182°C;

1H NMR (400 MHz, CDCl3) δ 8,13 (d, J=8,4 Hz, 2H), to 6.57 (d, J=8,4 Hz, 2H), 5,10 (s, 1H), was 4.02 (s, 2H), 3,85 (s, 3H).

Stage 2. Methyl ester [(2-chloroacetyl)-(4-trifloromethyl)-amino]-acetic acid. To a suspension of ester methyl 4-nitrophenylamino-acetic acid (3.0 g, of 14.2 mmol) in toluene (30 ml) add chlorocatechol (3 ml, excess). The solution is heated to 80°C for 1 hour, the resulting solid is dissolved. Then RA the solution is cooled and concentrated, and then the residual solid is recrystallized from methyl alcohol, which gives the ester (3.5 g) as a solid light yellow colour: melting point 106-109°C;

1H NMR (400 MHz, CDCl3) δ at 8.36 (d, J=8,4 Hz, 2H), 7,65 (d, J=8,4 Hz, 2H), 4,42 (s, 2H), 3,93 (s, 2H), 3,79 (s, 3H);

MS (Mass spectrometry)m/z286 (M+).

Stage 3. 1-(4-AMINOPHENYL)-4-(4-trifloromethyl)-piperazine-2,5-dione. The product of stage 2 (0.6 g, 2.3 mmol) is combined with 4-cryptomaterial (0,81 g, 4.6 mmol), and the substance is heated to 140°C for 90 minutes. The residual solid was stirred with dichloromethane (50 ml) and filtered to remove cleaners containing hydrochloride salt of aniline, and then the remainder of the concentrate and purify. Chromatography (elution with a mixture of ethyl acetate-hexanol) provides nitrophenyl-piperazinone (0,44 g) as a solid white color, melting point p.223-224°C. Recovery of the nitro group using a palladium catalyst on a carbon carrier (Pd/C) under the conditions described above, the network specified in the title amine in the form of a solid white color: melting point 250°C with decomposition;

1H NMR (400 MHz, CDCl3) δ 7,4 (d, J=8.5 Hz, 2H), 7,33 (d, J=8.6 Hz, 2H), 7,12 (d, J=8.7 Hz, 2H), 6.75 in (d, J=8.7 Hz, 2H), and 4.5 (s, 2H), of 4.45 (s, 2H);

MS (Mass spectrometry)m/z366,2 (M+N+).

Example 55: Obtain 5-(4-AMINOPHENYL)-3-(4-trifloromethyl the Il)-3 N-[1,3,4]oxadiazol-2-it

5-(4-Nitrophenyl)-3-(4-triptoreline)-3N-[1,3,4]oxadiazol-2-it is produced by processing the correspondingN'-(4-triptoreline)-hydrazide of 4-nitrobenzoic acid with phosgene, using the conditions described in the publication: Reimlinger et al.Chem. Ber. 1970, 103, 1934. The nitro-group is then reduced to amine by treatment with hydrogen in the presence of palladium catalyst on a carbon carrier (Pd/C) in ethanol: melting point 160-163°C;

1H NMR (400 MHz, CDCl3) δ 8,1 (d, J=8,4 Hz, 2H), to 7.75 (m, 4H), to 6.75 (d, J=8,4 Hz, 2H), 4,1 (Shir.s, 2H);

MS (Mass spectrometry)m/z322,6 (M+N+).

Example 56: Receivingtert-butyl ether complex {4-[1-(4-pentafluorophenyl)-1H-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 1)

A solution of 4-[1-(4-pentafluorophenyl)-1N-[1,2,4]triazole-3-yl]-phenylamine (1.0 g, 2.7 mmol) in anhydrous tetrahydrofuran (8 ml) is stirred, and at the same time, one portion addpair-nitrophenyl-chloroformate (0,60 g, 3 mmol)and the solution left to mix for 3 hours. The resulting solid is filtered off and dried in air. A smaller part of thepair-nitrophenylacetate (152 mg, 0.28 mmol) suspended in anhydrous tetrahydrofuran (3 ml). To this is added 2-methyl-2-propanol (41 mg, 0.32 mmol) in anhydrous tetrahydrofuran (1 ml), then add one portion of NaH (60%dispersion in mineral oil, 26 mg, 0.67 mmol). Additional dehydrated tetrahydrofuran (1 ml) used for wiping sections, and so on. The solution is heated to 60°C (outdoor) for 1.5 hours, at which point analysis by thin layer chromatography (TLC) (ethyl acetate/hexane/dichloromethane/acetone, 3:3:3:1) shows no starting material. The mixture is cooled and allowed to mix at 25°C for 20 hours. The mixture is cooled, poured into a mixture of ice-water (50 ml), and extracted with ethyl acetate (3×50 ml). The combined extracts washed with saturated aqueous NaCl (75 ml), dried (Na2SO4), filtered and concentrated. Obremenitve - high performance liquid chromatography (RP-HPLC) (gradient elution with a mixture of water-acetonitrile in an environment free acid) provides specified in the title compound (31 mg, 23%) as a solid off-white color: melting point 205-209°C;

1H NMR (400 MHz, CDCl3) δ 8,55 (s, 1H), 8,12 (d, J=9.0 Hz, 2H), 7,80 (d, J=9,3 Hz, 2H), of 7.48 (d, J=8,8 Hz, 2H), 7,38 (d, J=9.0 Hz, 2H), return of 6.58 (s, 1H), and 1.54 (s, 9H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z471 (M+H), 469 (M-N).

Compound 2 in Table 1 are synthesized as in Example 56.

Example 57: Obtain 1-(5-ethoxy-pyrimidine-2-yl)-1-mutilative of ester {4-[1-(4-trifloromethyl)-1 N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 3)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]benzoyl-azide (204 mg, 0.55 mmol) wash dehydrated toluene (2 ml)and the mixture heated to 110°C and stirred at that temperature for 1.5 hours. During heating of the observed gas. The mixture is cooled, and then add the alcohol (106 mg, 0.59 mmol) and NaH (60% dispersion in mineral oil; 76 mg, 1.9 mmol). The mixture is stirred at 25°C for 18 hours. The mixture is then poured into H2About (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organic extracts dried over Na2SO4, filtered and concentrated, giving a residue of a light reddish-brown color. Column chromatography on silica gel (cyclohexane:ethyl acetate:dichloromethane:acetone, 3:3:3:1) gives specified in the title compound (97 mg, 34%) as a solid light-reddish-brown colour: melting point 168-171°C;

1H NMR (400 MHz, CDCl3) δ charged 8.52 (s, 1H), of 8.37 (s, 2H), 8,08 (d, J=9.0 Hz, 2H), to 7.77 (d, J=8,9 Hz, 2H), 7,42 (d, J=8.7 Hz, 2H), was 7.36 (d, J=9.0 Hz, 2H), 6,91 (s, 1H), 4,12 (kV, J=7,0 Hz, 2H), 1,87 (s, 6H), of 1.44 (t, J=6.9 Hz, 3H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z529 (M+H), 527 (M-H); HRMS-ESI (Mass spectrometry high-resolution ionization elektrorazpredelenie) (m/z): [M]+calculated for C25H23F N6O4, 528,1727; found, 528,1730.

Compounds 4-8 in Table 1 are synthesized as in Example 57.

Example 58: Obtain 1-methyl-pentalofos of ester {4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 9)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (131 mg, 0,350 mmol) suspended in anhydrous toluene (1.0 ml). To the resulting suspension is added 2-hexanol (221 μl, of 1.75 mmol) in one portion. The suspension off-white color then heated to 100°C (outside). After the analysis UPLC (ultra-Efficient liquid chromatography) shows total expenditure original substances, the solution is light yellow cooled to 23°C and concentrated. Chromatography on silica gel (Column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 20%-40%-75%) provides specified in the title compound (134 mg, 85%) as a solid white color: melting point 111-113°C;

1H NMR (300 MHz, CDCl3) δ 8,54 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), 7,37 (DD, J=9,0, 0.8 Hz, 2H), 6,76 (s, 1H), 5,00 of 4.83 (m, 1H), 1,76-of 1.44 (m, 2H), 1,44 to 1.31 (m, 4H), of 1.29 (d, J=6,3 Hz, 3H), of 0.91 (t, J=7.0 Hz, 3H); ESIMS m/z 449 (M+H), 447 (M-H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z449 (M+H), 447 (M-H); HRMS-ESI (Mass spectrometry high p is resheniya with ionization elektrorazpredelenie) ( m/z): [M]+calculated for C22H23F3N4O3, 448,172; found, 448,173.

Compound 10 in Table 1 are synthesized as in Example 58.

Example 59: Obtaining 1,1-dimethyl-2-phenyl-ethyl ether complex {4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 11)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (93 mg, 0,248 mmol) suspended in anhydrous toluene (0,71 ml). To the resulting suspension is added 2-methyl-1-phenyl-2-propanol (191 μl, of 1.24 mmol) in one portion. The suspension off-white color then heated to 100°C (outside). After the analysis UPLC (ultra-Efficient liquid chromatography) shows total expenditure original substances, the yellow suspension is cooled to 23°C, filtered through a Frit of medium porosity, and concentrate. Chromatography on silica gel (Column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 10%-40%-75%) provides specified in the title compound (71 mg, 58%) as a solid white color: melting point 153 to 155°C;

1H NMR (300 MHz, CDCl3) δ 8,54 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.5 Hz, 2H), 7,38 (d, J=8.6 Hz, 2H), 7,34-7,17 (m, 5H), is 6.61 (s, 1H), 3,19 (s, 2H), 1,53 (s, 6H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie m/z497 (M+H), 495 (M-H); HRMS-ESI (Mass spectrometry high-resolution ionization elektrorazpredelenie) (m/z): [M]+calculated for C26H23F3N4O3, 496,172; found, 496,172.

Example 60: Obtaining 1,1-dimethyl-prop-2-innovage of ester {4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 12)

2-Methyl-3-butyn-2-ol (48 μl, 0.44 mmol) are added to a solution of triphosgene (42 mg, 0.14 mmol) and pyridine (38 μl, 0.47 mmol) in dichloromethane (1.0 ml) at 23°C. During the addition of alcohol see greenhouse gas emissions, and observe the formation of sludge. The resulting suspension was stirred at 23°C for 1 hour. Stirring is stopped, the solid substance is allowed to settle to the bottom of the flask, and the supernatant added via cannula to a suspension of 4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenylamine (100 mg, 0,312 mmol) and pyridine (38 μl, 0.47 mmol) in dichloromethane (1.0 ml) at 23°C. Observe the formation of a thick precipitate. At this point in time analysis by thin layer chromatography (TLC) shows the presence of some remaining original substance, therefore, is equivalent to the number of triphosgene/pyridine/ethanol connect the same way as above, and the resulting supernatant re-add to Ani the in-containing mixture. After stirring for an additional 3 hours at 23°C, the reaction mixture was diluted by 30% ethyl acetate in hexane (10 ml), and fine white precipitate is filtered by the coarse Frit. The filtrate is light yellow concentrated, and the resulting yellow oil purified by chromatography on silica gel (column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 10%-25%-50%) with the provision specified in the title compound (55 mg, 41%) as a solid white color: melting point 164-165°C;

1H NMR (400 MHz, CDCl3) δ 8,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,53 (d, J=8.5 Hz, 2H), 7,38 (d, J=8,8 Hz, 2H), 6.73 x (s, 1H), 2,61 (s, 1H), 1.77 in (s, 6H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z431 (M+H); HRMS-ESI (Mass spectrometry high-resolution ionization elektrorazpredelenie) (m/z): [M]+calculated for C21H17F3N4O3, 430,125; found, 430,126.

Example 61: Obtaining 1,1-dimethyl-prop-2-innovage of ester {4-[1-(4-triptoreline)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 13)

4-[1-(4-Triptoreline)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (137 mg, 0,383 mmol) suspended in anhydrous toluene (1.5 ml). To the resulting suspension is added 2-ethyl-3-butyn-2-ol (187 μl, at 1.91 mmol), then triethylamine (264 μl, at 1.91 mmol). The suspension off-white color then heated to 100°C (outside). After the analysis UPLC (ultra-Efficient liquid chromatography) shows total expenditure original substances, the yellow suspension is cooled to 23°C. and poured into 50%ethyl acetate in hexano. The suspension off-white color then filtered through a Frit of medium porosity, and concentrate. Chromatography on silica gel (Column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 10%-40%-75%) provides specified in the title compound (20 mg, 13%) as a solid white color: melting point 187-189°C;

1H NMR (400 MHz, CDCl3) δ 8,64 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), of 7.90 (d, J=8,4 Hz, 2H), 7,79 (d, J=8.6 Hz, 2H), 7,53 (d, J=8.6 Hz, 2H), 6,76 (s, 1H), 2,61 (s, 1H), 1.77 in (s, 6H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z415 (M+H), 413 (M-H); HRMS-ESI (Mass spectrometry high-resolution ionization elektrorazpredelenie) (m/z): [M]+calculated for C21H17F3N4O2, 414,130; found, 414,131.

Example 62: Receiving cyano-dimethyl-methyl complex ester {4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 14)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (107 is g, 0,286 mmol) suspended in anhydrous toluene (1.0 ml). To the resulting suspension is added 2-cyano-2-propanol (78 μl, 0,858 mmol). The suspension off-white color then heated to 90°C (outside). Within 10 seconds at this temperature, the suspension becomes homogeneous, and there is a vigorous evolution of gas. After an additional 10 minutes at this temperature, observe the formation of sludge. After the analysis UPLC (ultra-Efficient liquid chromatography) shows total expenditure original substances, the yellow suspension is cooled to 23°C and poured into hexane. The suspension off-white color then filtered through a Frit of medium porosity, and concentrate. Chromatography on silica gel (Column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 20%-40%-75%) provides specified in the title compound (7 mg, 6%) as a solid light yellow colour: melting point 172-175°C;

1H NMR (300 MHz, CDCl3) δ 8,55 (s, 1H), 8,16 (d, J=8.6 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,52 (d, J=8,4 Hz, 2H), 7,38 (d, J=8.7 Hz, 2H), 6,79 (s, 1H), of 1.84 (s, 6H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z432 (M+H), 430 (M-H).

Example 63: Receive 1-cyclopropyl-ethyl ether complex 4-{4-[1-(4-trifloromethyl)-1N-[1,2,4]-triazole-3-yl]-phenyl}-carbamino acid (Compound 15)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (84 mg, 0,225 mmol) suspended in anhydrous toluene (0,65 ml). To the resulting suspension was added 1-cyclopropylethyl alcohol (109 μl, 1.12 mmol). The suspension off-white color then heated to 90°C (outside). Within 10 seconds at this temperature, the suspension becomes homogeneous, and there is a vigorous evolution of gas. After 1 hour, slightly turbid yellow solution is cooled to 23°C and concentrated. Chromatography on silica gel (column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 10%-25%-50%) provides the extracted starting material (20 mg, 24%) as a solid white color along with the specified title compound (67 mg, 69%) as a solid white color: melting point 123-124°C;

1H NMR (400 MHz, CDCl3) δ 8,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.6 Hz, 2H), 7,37 (d, J=8.6 Hz, 2H), 6,85 (s, 1H), 4,34 (doctor kV, J=12,7, 6.3 Hz, 1H), 1,38 (d, J=6.3 Hz, 3H), 1,14-of 0.95 (m, 1H), 0,67 at 0.42 (m, 3H), 0,29 (DDD, J=7,6, 6,5, 3.8 Hz, 1H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z433 (M+H), 431 (M-H).

Example 64: Obtain 1-cyclohexyl-ethyl ether complex 4-{4-[1-(4-trifloromethyl)-1N-[1,2,4]-triazole-3-yl]-phenyl}-carbamino acid (Compound 16)

4-[1-(4-Trifloromethyl)-1H/i> -[1,2,4]triazole-3-yl]-benzoyl-azide (90 mg, 0,241 mmol) suspended in anhydrous toluene (0,70 ml). To the resulting suspension type (1-cyclohexyl)ethyl alcohol (166 μl, 1.20 mmol). The suspension off-white color then heated to 90°C (outside). Within 10 seconds at this temperature, the suspension becomes homogeneous, and there is a vigorous evolution of gas. After an additional 10 minutes at this temperature, observe the formation of a certain amount of sediment. After the analysis UPLC (ultra-Efficient liquid chromatography) shows total expenditure original substances, the yellow suspension is cooled to 23°C. and poured into a mixture, representing 25% ethyl acetate in hexane. The suspension off-white color then filtered through a Frit of medium porosity, and concentrate. Chromatography on silica gel (Column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 15%-30%-50%) provides specified in the title compound (98 mg, 86%) as a solid white color: melting point 146-148°C;

1H NMR (400 MHz, CDCl3) δ 8,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,52 (d, J=8.5 Hz, 2H), was 7.36 (d, J=8,4 Hz, 2H), 6.89 in (s, 1H), amounts to 4.76 (t, J=6.3 Hz, 1H), 2,13-to 1.61 (m, 4H), 1,49 (TDD, J=11,8, 6,1, 3.1 Hz, 1H), 1,24 (d, J=6.4 Hz, 3H), 1,22-to 0.96 (m, 6H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z475 (M+H), 473 (M-N).

Compounds 17-22 in Table 1 are synthesized as in Example 64.

Example 65: Receipt of ester ethyl 4-methyl-4-{4-[1-(4-trifloromethyl)-1N-[1,2,4]-triazole-3-yl]-phenylcarbamoyloxy}-Penta-2-invoi acid (Compound 23)

1,1-Dimethyl-prop-2-injuly ester 4-[1-(4-triptoreline)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 13; 11981077; 88 mg, 0.20 mmol) dissolved in anhydrous tetrahydrofuran (2.0 ml) and cooled to -78°C. and Then added dropwise n-utility (164 μl of 2.5 M solution in hexane, 0,410 mmol). The mixture is stirred for additional 20 minutes at -78°C, and then add one portion of ethylchloride (24 μl, 0.25 mmol). The mixture is stirred for a further 30 minutes at -78°C and then warmed to 23°C. the Mixture decompose polysystem aqueous solution of NH4Cl and extracted with a mixture representing 50% ethyl acetate in hexane. The combined organic layers are then washed with brine, dried over Na2SO4and concentrate. Chromatography on silica gel (column SNAP 10 g Biotage; gradient elution with a mixture of ethyl acetate/hexane, 15%-30%-50%-75%) followed by recrystallization from a mixture of diethyl ether/hexane provide specified in the title compound (10 mg, 10%) as a solid yellow color: melting point 183-188°C;

H NMR (300 MHz, CDCl3) δ to 8.57 (s, 1H), 8,27 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.1 Hz, 2H), 7,40 (pseudo d, J=8.7 Hz, 4H), 4,99 (s, 1H), 3,66 (kV, J=7,1 Hz, 2H), 1.70 to (s, 6H), and 0.98 (t, J=7,1 Hz, 3H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z503 (M+H).

Example 66: Getting 2,2,3,3,3-pendaftar-1-methyl-propyl ether complex {4-[1-(trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 24)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (77 mg, 0,206 mmol) suspended in anhydrous toluene (0,60 ml). To the resulting suspension add 3,3,4,4,4-pendaftar-2-butanol (120 μl, of 1.03 mmol). The suspension off-white color then heated to 90°C (outside). Within 10 seconds at this temperature, the suspension becomes homogeneous, and there is a vigorous evolution of gas. After an additional 10 minutes at this temperature, there is the formation of a small amount of sediment. After the analysis UPLC (ultra-Efficient liquid chromatography) shows total expenditure original substances, the yellow suspension is cooled to 23°C. and poured into a mixture, representing 25% ethyl acetate in hexane. The suspension off-white color is filtered through a Frit of medium porosity, and concentrate with the provision specified in the title compound (80 mg, 76%) in VI is e solid off-white color: melting point 171-173°C;

1H NMR (400 MHz, DMSO-d6) δ 10,33 (s, 1H), 9,38 (s, 1H), 8,10-to 7.99 (m, 4H), to 7.67-7,58 (m, 4H), 5,81-5,23 (m, 1H), 1,47 (d, J=6.3 Hz, 3H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z511 (M+H), 509 (M-H); HRMS-ESI (Mass spectrometry high-resolution ionization elektrorazpredelenie) (m/z): [M]+calculated for C20H14F8N4O3, 510,0933; found, 510,0998.

Compound 25 in Table 1 are synthesized as in Example 66.

Example 67: Getting ethyl ether complex 2-{4-[1-(4-trifloromethyl)-1N-[1,2,4]-triazole-3-yl]-phenylcarbamoyloxy}-hexanoic acid (Compound 26)

4-[1-(4-Trifloromethyl)-1N-[1,2,4]triazole-3-yl]-benzoyl-azide (90 mg, 0,241 mmol) suspended in anhydrous toluene (0,70 ml). The suspension off-white color then heated to 90°C (external) and stirred for 30 minutes. Within 10 seconds at this temperature, the suspension becomes homogeneous, and there is a vigorous evolution of gas. Slightly cloudy yellow solution is cooled to 23°C, and add ethyl-2-gidroksicarbonat (52 μl, 1.20 mmol). The mixture was stirred at 23°C for 15 hours, and then poured into a mixture, representing 25% ethyl acetate in hexane. The suspension off-white color is filtered through a Frit of medium porosity, and concentrate. Chromatography on silica gel (SNAP 10 g Biotage, gradient elution with a mixture of ethyl acetate/hexane, 15%-30%-50%-75%) provides specified in the title compound (10 mg, 8%) as a solid white color: melting point 135-139°C;

1H NMR (300 MHz, CDCl3) δ 8,55 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,51 (d, J=8,8 Hz, 2H), 7,38 (DD, J=9,0, 0.8 Hz, 2H), 6,97 (s, 1H), 5,08 (DD, J=7,2, 5.4 Hz, 1H), 4,25 (kV, J=7,1 Hz, 2H), 1,95-of 1.80 (m, 2H), 1,52 is 1.34 (m, 4H), of 1.30 (t, J=7,1 Hz, 3H), of 0.93 (t, J=7.2 Hz, 3H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z507 (M+H), 505 (M-H).

Example 68: Obtain 1-(4-(trifluoromethyl)phenyl)ethyl 4-(1-(4-(trifluoromethyl)phenyl)-1N-1,2,4-triazole-3-yl)-phenylcarbamate (Compound 27)

4-[1-(4-Trifluoromethyl)phenyl)-1N-1,2,4-triazole-3-yl)-benzoyl-azide (62.5 mg, 0,174 mmol) suspended in anhydrous toluene (0,498 ml). To the resulting suspension was added 1-(4-(trifluoromethyl)phenyl)ethanol (to 36.5 mg, 0,192 mmol). The suspension off-white color then heated to 100°C. (external) for 18 hours and then cooled to ambient temperature. The reaction mixture was applied directly to a column of silica gel, gradient elution with a mixture of ethyl acetate/hexane (10%-50%-100%) provides specified in the title compound (57.6 mg, 63%) as a solid white color: melting point 155,5-158,5°C;

1H NMR (400 MHz, CDCl3) δ to 8.62 (s, 1H), 8,15 (d, J=8,8 Hz, 2), of 7.90 (d, J=8.5 Hz, 2H), 7,79 (d, J=8.5 Hz, 2H), to 7.64 (d, J=8,2 Hz, 2H), 7,51 (pseudo t, J=8,4 Hz, 4H), 6,79 (s, 1H), 5,95 (kV, J=6,6 Hz, 1H), and 1.63 (d, J=6,7 Hz, 3H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z521 (M+H), 519 (M-H).

Example 69: Getting carbamates - a Common Way And

Acylated suspended in anhydrous toluene (0.35 M). To the resulting suspension add the corresponding alcohol (1.20 equiv.). The suspension is heated to 100°C. (external) for 4-24 hours and then cooled to ambient temperature. The product emit vacuum filtered or purified column chromatography on silica gel (after application of the substance directly on the column) using a gradient elution with a mixture of ethyl acetate/hexane. In some cases, require additional purification by recrystallization. Commonly used solvents include chloroform-d, a mixture of diethyl ether/hexane, and diethyl ether/dichloromethane/hexane.

Connection 28-121 in Table 1 are synthesized as in Example 69.

Example 70: Getting carbamates - a Common Method In

Acylated suspended in anhydrous toluene (0.35 M). To the resulting suspension add the corresponding alcohol (1.20 equiv.). The suspension is heated to 100°C. (external) for 4-24 hours and then cooled to ambient temperature. Add triethylamine (1.50 equiv.)and the reaction mixture stirred at ambient temperature for an additional 1 hour. The product emit vacuum filtered or purified column chromatography on silica gel (after application of the substance directly on the column) using a gradient elution with a mixture of ethyl acetate/hexane.

Connection 122-129 synthesized as in Example 70.

Example 71: Obtain 1-(6-(trifluoromethyl)pyridin-3-yl)ethyl ethyl(4-(1-(4-(triptoreline)phenyl)-1H-1,2,4-triazole-3-yl)phenyl)carbamate (Compound 130)

1-(6-(Trifluoromethyl)pyridin-3-yl)ethyl 4-(1-(4-triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)phenylcarbamate (54 mg 0.10 mmol) dissolved in anhydrous dimethylformamide (0.5 ml) under nitrogen atmosphere and cooled to 0°C. Add NaH (60%suspension in mineral oil; 4.4 mg, 0.11 mmol)and the mixture stirred for 10 minutes at 0°C. Add Iodate (9 μl, 0.11 mmol), and the mixture is heated to ambient temperature and stirred for 1 hour. When the ambient temperature is added NaH (4 mg) and Iodate (5 ál) to facilitate the full withdrawal of the original substance. The mixture is decomposed with an aqueous solution of NH4Cl and extracted with a mixture comprising 80% ethyl acetate in hexane (×3). The combined organic layers washed with brine, dried over Na2SO4and concentrate. The crude product is applied onto a column of silica gel, gradient elution with a mixture of 8% ethyl acetate in hexane (15%-40%-80%) provides specified in the title compound (52.1 mg, 91%) as a oil light yellow:

IR-spectroscopy 3111, 2983, 2936, 1707, 1519, 1340, 1268, 1155 cm-1;

1H NMR (300 MHz, CDCl3) δ to 8.62 (s, J=a 10.6 Hz, 1H), 8,58 (s, 1H), 8,21 (d, J=8.5 Hz, 2H), 7,81 (d, J=9.0 Hz, 2H), 7,73-7,58 (m, 2H), 7,40 (d, J=8.5 Hz, 2H), 7,30 (d, J=8.5 Hz, 2H), 5,95 (kV, J=6,6 Hz, 1H), 3,84-3,70 (m, 2H), 1,53 (d, J=6.2 Hz, 3H), 1,19 (t, J=7,1 Hz, 3H);

HRMS-FAB (Mass spectrometry high-resolution bombardment of accelerated atoms)m/z[M+H]+calculated for C26H21F6N5O3, 565,1549; found, 565,1568.

Example 72: Receivetert-butyl methyl(4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)phenyl)carbamate (Compound 131)

tert-Butyl(4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)phenyl)carbamate (120 mg, 0,286 mmol) dissolved in anhydrous dimethylformamide (2.0 ml) under nitrogen atmosphere and cooled to 0°C. Add NaH (60%suspension in mineral oil, 15 mg, 0,372 mmol)and the mixture stirred for 10 minutes at 0°C. Add logmean (23 μl, 0,372 mmol), and the mixture is heated to ambient temperature and stirred for 1 hour. The mixture is decomposed with an aqueous solution of NH4Cl and extracted with a mixture comprising 80% ethyl acetate in hexane (×3). The combined organic layers washed with brine, dried over Na2SO4and concentrate. The crude product is applied onto a column of silica gel, and Gracie is the things elution with a mixture of ethyl acetate in hexane (15%-40%-80%) provides specified in the title compound (108,0 mg, 87%) as a solid white color: melting point 125-128°C;

1H NMR (400 MHz, CDCl3) δ 8,55 (s, 1H), 8,14 (d, J=8.6 Hz, 2H), 7,79 (d, J=8,9 Hz, 2H), 7,38 (d, J=9.8 Hz, 2H), 7,35 (d, J=8,8 Hz, 2H), and 3.31 (s, 3H), of 1.47 (s, 9H);

HRMS-FAB (Mass spectrometry high-resolution bombardment of accelerated atoms)m/z[M+H]+calculated for C21H21F3N4O3, 434,156; found, 434,157.

Example 73: ReceiveOmethyl 4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)phenylcarbamate (Compound 132)

Stage 1. 4-(1-(4-(Triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)aniline was dissolved in tetrahydrofuran (2.5 ml) to obtain the solution is reddish-brown color. Then add phenyl-chlorothionoformate (0,205 mg, 1,19 mmol). Instantly precipitated solid, and stirring becomes difficult. To facilitate mixing add additional tetrahydrofuran (2.5 ml). Add additional portion phenyl-chlorothionoformate (0,205 mg, 1,19 mmol), then triethylamine (0,38 ml, 2,80 mmol). The reaction mixture is decomposed with a saturated aqueous solution of NaHCO3and extracted with a mixture of 50% ethyl acetate in hexane. The organic layer was washed with aqueous solution of NaHCO3and brine, dried over Na2SO4and concentrate. Purification by chromatography on silica the Le (gradient elution with a mixture of ethyl acetate in hexane, 15%-30%-50%-80%) provides N,N-bis(typenex)-4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)aniline (0,472 g, 80%) as a solid yellow color: melting point 142-144°C;

1H NMR (400 MHz, CDCl3) δ 8,58 (s, 1H), 8.34 per (d, J=8.6 Hz, 2H), 7,80 (d, J=9.0 Hz, 2H), 7,66 (d, J=8.6 Hz, 2H), 7,49-7,34 (m, 6H), 7,34-7,28 (m, 2H), 7,26-7,13 (m, 4H);

HRMS-FAB (Mass spectrometry high-resolution bombardment of accelerated atoms)m/z[M+H]+calculated for C29H19F3N4O3S2, 592,085; found, 592,0861.

Stage 2. To a solution of the product of stage 1 in methyl alcohol (2.5 ml) and tetrahydrofuran (2.5 ml) is added NaOH (2.5 ml 1M aqueous solution). Instantly formed a thick yellow precipitate. Add additional tetrahydrofuran, methyl alcohol, and 1M NaOH solution (2.5 ml each), and get a clear solution yellow. The mixture is then poured into an aqueous solution of NaHCO3and extracted with a mixture of 50% ethyl acetate in hexane (×3). The combined organic layers washed with brine, dried over Na2SO4and concentrated to obtain solid yellow color. The solid is ground to powder with a mixture of 20% ethyl acetate in hexane, giving specified in the title compound (137 mg, 51%) as a solid white color. The filtrate is concentrated and purified by chromatography on silica gel (gradient elution see what sue ethyl acetate/hexane, 15%-40%-80%), with additional product (57.6 mg, 0,126 mmol, 22%): melting point 192-194°C;

1H NMR (300 MHz, DMSO-d6) δ made 11.32 (s, 1H), 9,39 (s, 1H), 8,14-to 7.95 (m, 4H), of 7.90-7,65 (width, 1H), 7.62mm (pseudo DD, J=9,0, 0.7 Hz, 2H), 7,60-7,40 (width, 1H), 4,01 (Shir.s, 3H);

HRMS-FAB (Mass spectrometry high-resolution bombardment of accelerated atoms)m/z[M+H]+calculated for C17H13F3N4O2S, 394,071; found, 394,0712.

Example 74: ReceiveO1-(6-(trifluoromethyl)pyridin-3-yl)ethyl 4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)phenylcarbamate (Compound 133)

In nitrogen atmosphere, to a cold dichloromethane, cooled in an ice bath, is added dropwise thiophosgene (0,56 mmol). To this solution is added a cold 0.2 mm solution of K2CO3(0.13 mmol). The reaction mixture is stirred for 10 minutes. 4-(1-(4-(Triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)aniline (0,56 mmol) is dissolved in dichloromethane and added dropwise to the above mixture. The reaction mixture was allowed to mix for an additional 10 minutes. Then add cold 0.6 mm solution of KOH (to 0.92 mmol). After 30 minutes, the reaction mixture is diluted with dichloromethane and washed with water and brine. The organic layer is dried over MgSO4and concentrate. Crude isothiocyanate use without on the further purification in the next stage.

To a suspension of NaH (9,2 mg of 60%suspension in mineral oil, 0,229 mmol) in tetrahydrofuran (1 ml) at 0°C was added 1-(6-(trifluoromethyl)pyridin-3-yl)ethanol (43,7 mg, 0,229 mmol) in phenylmethane (0.4 ml). The mixture is heated to ambient temperature and stirred for 15 minutes, and then added via cannula mentioned above isothiocyanate (75,6 mg, 0,209 mmol) in tetrahydrofuran (1 ml). After stirring for 20 minutes, the mixture is decomposed by adding an aqueous solution of NH4Cl and extracted with ethyl acetate (×3). The combined organic extracts washed with brine, dried over Na2SO4and concentrate. The crude product is applied onto a column of silica gel, gradient elution with a mixture of ethyl acetate/hexane (15%-40%-65%) provides specified in the title compound (88,2 mg, 77%) as a solid off-white color: melting point 186,5-188°C;

1H NMR (300 MHz, CDCl3) δ 8,76 (s, 1H), 8,58 (s, 1H), and 8.50 (s, 1H), 8,19 (d, J=8.7 Hz, 2H), to $ 7.91-7,83 (m, 1H), 7,80 (d, J=9.1 Hz, 2H), 7,69 (d, J=8,1 Hz, 1H), 7,49-7,29 (m, 4H), 6,68 (kV, J=6,7 Hz, 1H), 1,76 (d, J=6.6 Hz, 3H);

HRMS-FAB (Mass spectrometry high-resolution bombardment of accelerated atoms)m/z[M+H]+calculated for C24H17F6N5O2S, 553,101; found, 553,1006.

Example 75: ReceiveO4-forfinal 4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)phenylcarbamate (With the Association 134)

A 25-ml round bottom flask add 4-(1-(4-(triptoreline)phenyl)-1N-1,2,4-triazole-3-yl)aniline (200 mg, 0,624 mmol),About-4-forfinal acid chloride-Topolino acid (238 mg, 1,249 mmol), and triethylamine (0,348 ml, 2,498 mmol) in tetrahydrofuran (5 ml). The solution is stirred at ambient conditions for 2 hours before removing the solvent under reduced pressure. The crude product is introduced into a column of silica gel and spend gradient elution with a mixture of ethyl acetate/hexane with the provision specified in the title compound (50 mg, 0,105 mmol, 17%) as a solid yellow color: melting point 164-169°C;

1H NMR (400 MHz, DMSO-d6) δ 9,42 (s, 1H), 8,19-of 8.04 (m, 6H), 7,97 (Shir.s, 1H), 7,66-EUR 7.57 (d, J=8,24 Hz, 2H), 7,33-7,19 (m, 4H);

ESIMS (Mass spectrometry with ionization by elektrorazpredelenie)m/z475 (M+1).

Example 76: Obtain methyl 4-(1-(4-(perforators)phenyl)-1N-1,2,4-triazole-3-yl)phenylcarbamate (Compound 135)

4-Nitrophenyl 4-(1-(4-(perforators)phenyl)-1N-1,2,4-triazole-3-yl)phenylcarbamate (1.90 g, 3,55 mmol) is suspended in methyl alcohol (15 ml) and cooled in a bath of dry ice in acetone at -10°C. for 10 minutes is added dropwise sodium methoxide (1,33 ml of 30% wt. solution in methyl alcohol, 7,10 mmol). The resulting suspension is bright W is logo color heated to ambient temperature and poured into ice water (150 ml). After vigorous stirring for 10 minutes, the mixture is filtered on a Buechner funnel. Solid reddish-brown color, rinsed with water and dried in air. Recrystallization from a mixture of methyl alcohol/water provides specified in the title compound (0,989 g, 65%) as a solid reddish-brown colour: melting point 183-184,5°C;

1H NMR (300 MHz, CDCl3) δ 8,55 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.6 Hz, 2H), 7,38 (d, J=8,9 Hz, 2H), 6,79 (s, 1H), 3,80 (s, 3H);

HRMS-FAB (Mass spectrometry high-resolution bombardment of accelerated atoms)m/z[M+H]+calculated for C18H13F5N4O3, 428,0908; found, 428,0903.

Example 77: Obtain 4-nitrophenylamino of ester methyl-{4-(1-(4-(trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-carbamino acid (Compound 136)

A suspension of 4-[1-(4-triftormetilfosfinov)-1N-[1,2,4]triazole-3-yl]-phenylamine (1.2 g, 3.7 mmol) in ethanol (4 ml) is treated with 1N-benzotriazole (of 0.48 g, 4.0 mmol) and formaldehyde (0.5 ml 37%aqueous solution, 6 mmol)and the solution heated to 40°C for 10 minutes. After cooling, forms a solid, which is collected by filtration. Get 1,33 g triazole adduct in the form of a solid of light yellow color, melting point 185-87°C. This substance (1.2 g, of 2.66 mmol) was dissolved in tetrahydrofuran (20 ml) and treated by NaBH4(0.11 g, 2.9 mmol). The solution was stirred at ambient temperature for 30 minutes, then heated to the boiling point, which is carried out under reflux for 1 hour. After cooling, the solution was poured into water (30 ml) and extracted with diethyl ether. Drying and concentration, followed by chromatography on silica gel (hexane:ethyl acetate, 75:25) to give methyl-{4-[1-(4-trifloromethyl)-1N-[1,2,4]triazole-3-yl]-phenyl}-amine (0,76 g, 86%) as a solid white color, melting point 121-123°C;

1H NMR (300 MHz, CDCl3) δ 8,51 (s, 1H), 8,02 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,37 (d, J=8,3 Hz, 2H), of 6.68 (d, J=8,8 Hz, 2H), 3.96 points (s, 1H), 2.91 in (s, 3H);

EIMS (Mass spectrometry with ionization by electron impact)m/z499 (M+).

Part of this amine (0.11 g, 0.33 mmol) dissolved in anhydrous tetrahydrofuran (2 ml) and treated with 4-nitrophenyl-chloroformate (0,069 g, 0.34 mmol). The solid that is formed within 10 minutes, collected by filtration and dried in air, giving a solid off-white color (0.10 g): melting point 145-147°C;

1H NMR (300 MHz, CDCl3) δ 8,59 (s, 1H), 8,28 (d, J=8 Hz, 4H), 7,8 (d, J=8 Hz, 2H), 7,50 of 7.3 (m, 6 H) 3,55 (s, 3H);

EIMS (Mass spectrometry with ionization by electron impact)m/z/i> 499 (M+).

Compounds of experience in the fight against small scoops and scoops of cotton using the techniques described in the following examples and reflected in Table 2.

In each case, are presented in Table 2, the rating scale is as follows:

%The struggle (or Death)Score
50-100A
Less than 50B
Not testedC

Example 78: Insecticidal test against small scoops (Spodoptera exigua)

Bioassays on small scoop (BAW;Spodoptera exigua: Lepidoptera) is conducted using a test using 128-hole tablet with a nutrient medium. Three to five BAW larvae of the second age are placed in each well (3 ml) tablet with a nutrient medium that was pre-filled artificial nutrient medium (1 ml per well), which has been applied (in each of the eight holes) 50 µg/cm2the test compound (dissolved in 50 μl of a mixture of acetone-water, 90:10), and then leave to dry. The tablet cover with a transparent adhesive layer, and incubated at 25°C for six days in the regime of light-dark 14:10. The percentage of death R gastronaut for larvae in each well; the intensity of the action in eight holes then average. The results for both bioassays are shown in Table 2.

Example 79: Insecticidal test against cotton Cutworm (Helicoverpa zea)

Bioassays on cotton scoop (CEW;Helicoverpa zea: Lepidoptera) is conducted using a test using 128-hole tablet with a nutrient medium. Three to five CEW larvae of the second age are placed in each well (3 ml) tablet with a nutrient medium that was pre-filled artificial nutrient medium (1 ml per well), which has been applied (in each of the eight holes) 50 µg/cm2the test compound (dissolved in 50 μl of a mixture of acetone-water, 90:10), and then leave to dry. The tablet cover with a transparent adhesive layer, and incubated at 25°C for six days in the regime of light-dark 14:10. The percentage of deaths recorded for larvae in each well; the intensity of the action in eight holes then average. The results for both bioassays are shown in Table 2.

Connections are also facing in relation to aphid green peach using the techniques described in the following example, which is also reflected in Table 2.

In each case, are presented in Table 2, the rating scale is as follows:

%The struggle (or Gibel the) Score
80-100A
Less than 80B
Not testedC

Example 80: Insecticidal test against aphid green peach (Myzus persicaein the analysis of spray deciduous system of plants

As the test substrate using cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves. Seedlings infect 20-50 individuals aphid green peach (apterous adult insect and larva species with incomplete metamorphosis) one day before applying chemicals. Four pot of individual seedlings used for each treatment. Compound (2 mg) dissolved in 2 ml of solvent acetone/methanol (1:1), with basic solutions containing 1000 ppm.. Basic solutions were diluted in 5 times of 0.025%solution of Tween 20 in water to obtain a solution containing 200 ppm.. Portable Devilbiss atomizer is used to atomize the solution on both sides of cabbage leaves until runoff. Control plants (check processing solvent) are sprayed with only diluent. Before you make a selection, the treated plants are kept in a storage room during the three days at approximately 25°C and at a relative humidity (RH) of 40%. The evaluation is made by counting the number of live aphids per plant under a microscope. Insecticidal activity, calculated using the correction formula of Abbott presented in Table 2:

Corrector. %Control insect pests = 100*(X-Y)/X

where X = the number of live aphids on the plants processed for validation solvent

Y = the number of live aphids on treated compounds plants

DERIVED ON the BASIS of ACIDS AND SALTS AND SOLVATE

The compounds disclosed in this invention can be in the form pesticide acceptable salts accession acid.

As a non-limiting example, the functional amino group can form salts with hydrochloric, Hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzosulfimide, methansulfonate, econsultancy, hydroxyethanesulfonic, and hydroxyethanesulfonic acids.

In addition, as a non-limiting example, the functional group of the acid, may form salts, including salts derived from alkali or alkaline earth metals, and salts derived from ammonia and amines. Examples of preferable to the thiones include sodium, potassium, magnesium, and aminiya cations.

Salt is prepared by conducting contact “freely” main form with a sufficient amount of the desired acid, which gives the salt. “Free” basic forms may be regenerated by treatment of the salt with a suitable dilute aqueous solution of a base, such as dilute aqueous NaOH solution, diluted with aqueous potassium carbonate solution, dilute aqueous ammonia solution, and dilute aqueous sodium bicarbonate solution. As an example, in many cases, pesticide modify from turning into more water-soluble form, for example, dimethylamine salt and 2,4-dichlorophenoxy-acetic acid is more soluble form of 2,4-dichlorophenoxy-acetic acid, a well-known herbicide.

The compounds disclosed in this invention can also form stable complexes with solvent molecules, which remain intact after removal of the compounds is not related to the complex molecules of the solvent. These complexes often referred to as a "solvate".

STEREOISOMERS

Some compounds disclosed in this document can exist in the form of one or more stereoisomers. Different stereoisomers include geometric isomers, diastereomers, and enantiomers. Thus, the compounds disclosed in E. the second invention, include racemic mixtures, individual stereoisomers and optically active mixtures. Specialists in this field will be clear that one stereoisomer may be more active than others. Individual stereoisomers and optically active compounds can be obtained according to the methods of selective synthesis according to the methods commonly used synthesis using dedicated/separated source substances, or by commonly used methods of separation.

INSECT PESTS

In yet another embodiment, the invention disclosed in this document can be used to control insect pests.

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsPhylum Nematoda(class Nematoda).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsPhylum Arthropoda(type arthropods).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsSubphylum Chelicerata(subtype Chelicerata).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsClass Arachnida(class of PAH is obraznye).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsSubphylum Myriapoda(subtype millipedes).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsClass Symphyla(Class Of Simpily).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsSubphylum Hexapoda(subtype shestyorki).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsClass Insecta(Class Insecta).

In yet another embodiment, the invention disclosed in this document can be used to control insect pestsColoptera(the order of beetles). A non-exhaustive list of these pests includesAcanthoscelides spp. (weevils), Acanthoscelides obtectus(bean weevil),Agrilus planipennis(bug grinder or the bark beetle, is destructive to ash),Agriotes spp.(wireworms),Anoplophora glabripennis(Asian Longhorn beetle),Anthonomus spp.(weevils-vetoed),Anthonomus grandis(weevil cotton),Aphidius spp., Apion spp.(clover weevils-Samedi and clover stableid),Apogonia spp.(cerovina larva),Ataenius spretulus Atomaria linearis(baby beet), Aulacophore spp., Bothynoderes punctiventris(beet weevil),Bruchus spp.(weevil-bruchus),Brucchus pisorum(pea weevil),Cacoesia spp., Callosobruchus maculatus(caryopsis chetyrehbalnoy),Carpophilus hemipteras(bestanka Heteroptera),Cassida vittata, Cerosterna spp., Cerotoma spp.(leaf),Cerotoma trifurcate(beetle leaf),Ceutorhynchus spp.(krutogoloviy seed), Ceutorhynchus assimilis(rape-seed stratocumuli),Ceutorhynchus napi(stratocumuli small),Chaetocnema spp.(leaf),Colaspis spp.(soil beetles),Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar(fruit weevil),Cotinus nitidis(beetle brilliant green),Crioceris asparagi(rattle which is green),Cryptolestes ferrugineus(mucoid red),Cryptolestes pusillus(mucoid tiny),Cryptolestes turcicus(mucoid Turkish),Ctenicera spp.(wireworms),Curculio spp.(weevils/elephants),Cyclocephala spp.(cerubidine larvae of the beetle),Cylindrocpturus adspersus(stratocumuli stem sunflower),Deporaus marginatus(mango weevils-listorezy),Dermestes lardarius(Coheed ham),Dermestes maculates(Coheed spotted),Diabrotica spp.(chrysolemids),Epilachna varivestis(Mexican bean weevil),Faustinus cubae, Hylobius pales(beetle weevil),Hypera spp.(weevils/elephants),Hypera postica(beetle weevil),Heperdoes spp.(weevil-Hyperodes),Hypothenemus hampei(borer),Ips spp.(bark),Lasioderma serricorn (tobacco beetle),Leptinotarsa decemlineata(Colorado potato beetle),Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus(weevil rice water),Lyctus spp.(beetles/bugs-dravograd),Maecolaspis joliveti, Megascelis spp., Melanotus communis, Meligethes spp., Meligethes aeneus(the rape pollen beetle),Melolontha melolontha(beetle may West),Oberea brevis, Oberea linearis, Oryctes rhinoceros(bug date palm),Oryzaephilus mercator(plasmatica peanut),Oryzaephilus surinamensis(mucoid Suriname),Otiorhynchus spp.(weevils),Oulema melanopus(plavica krasnogruda),Oulema oryzae, Pantomorus spp.(weevils),Phyllophaga spp.(chafer),Phyllophaga cuyabana,Phyllotreta spp.(leaf),Phynchites spp., Popillia japonica(garden chafer Japanese),Prostephanus truncates(kapusnik),Rhizopertha dominica(grinder grain),Rhizotrogus spp.(kornegay - Amphimallon majalis),Rhynchophorus spp.(palm weevils),Scolytus spp.(beetles),Shenophorus spp.(weevil),Sitona lineatus(elephant striped pea),Sitophilus spp.(granary weevil grain),Sitophilus granaries(granary weevil common),Sitophilus oryzae(rice weevil),Stegobium paniceum(grinder bread),Tribolium spp.(khruschak large flour),Tribolium castaneum(khruschak chestnut),Tribolium confusum(khruschak small flour),Trogoderma variabile(trogoderma variable) andZabrus tenebioidesbut is not limited to this.

In another embodiment, the invention disclosed in this document can be used to combat agricultural pests Dermaptera(earwig (Historiae)).

In yet another embodiment, the invention disclosed in this document can be used to combat insect-pestDictyoptera(cockroaches). A non-exhaustive list of these pests includes Blattella germanica (Prusak (red cockroach)), Blatta orientalis (cockroach black), Parcoblatta pennylvanica(cockroach woods of Pennsylvania), Periplaneta americana (American cockroach), Periplaneta australoasiae (Australian cockroach), Periplaneta brunnea (brown cockroach), Periplaneta fuliginosa (Smokybrown cockroach), Pyncoselus suninamensis (cockroach Suriname) and Supella longipalpa (cockroach with brown stripes), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be used to control insect pests Diptera (true flies). A non-exhaustive list of these pests includes Aedes spp. (insects), Agromyza frontella (mol-pestryanka Lozanova), Agromyza spp. (leaf-mining fly), Anastrepha spp. (fruit fly), Anastrepha suspensa (Caribbean fruit fly), Anopheles spp. (mosquitoes), Batrocera spp. (fruit fly), Bactrocera cucurbitae (melon fly), Bactrocera dorsalis (Oriental fruit fly), Ceratitis spp. (fruit fly), Ceratitis capitata (Mediterranean fruit fly), Chrysops spp. (deer flies), Cochliomyia spp. (larvae of the screwworm), Contarinia spp. (Midge), Culex spp. (mosquitoes koleksi), Dasineura spp. (Midge), Dasineura brassicae (Midge cabbage), Delia spp., Dela platura (the larva of a fly germ), Drosophila spp. (Drosophila), Fannia spp. (milichiidae (house flies)), Fannia canicularis (fly small room), Fannia scalaris (fly ladder), Gasterophilus intestinalis (stomach gadfly), Gracillia perseae, Haematobia irritans (gigalo cow small), Hylemyia spp. (cabbage fly), Hypoderma lineatum (larva bullish striped gadfly), Liriomyza spp. (leaf miner flies), Liriomyza brassica (miner cruciferous), Melophagus ovinus (runes sheep), Musca spp. (true fly), Musca autumnalis (fly ordinary field), Musca domestica (housefly room), Oestrus ovis (sheep gadfly abdominal), Oscinella frit (fly Swedish), Pegomyia betae (fly beet), Phorbia spp., Psila rosae (carrot fly), Rhagoletis cerasi (fly cherry), Rhagoletis pomonella (larva of petrotrace Apple), Sitodiplosis mosellana (Midge cereal orange), Stomoxys calcitrans (gigalo autumn (ordinary)), Tabanus spp. (horseflies) and Tipula spp. (crane flies), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be used to control insect pests Hemiptera (true bugs true bugs). A non-exhaustive list of these pests includes Acrosternum hilare (defenders), Blissus leucopterus (bug-bug North American wheat), Calocoris norvegicus (klopik potato), Cimex hemipterus (tropical bed bug), Cimex lectularius (bed bug), Dagbertus fasciatus, Dichelops furcatus, Dysdercus suturellus (Krasnogo cotton), Edessa meditabunda, Eurygaster maura (bug Taurus), Euschistus eros, Euschistus servus (plant bug), Helopeltis antonii, Helopeltis theivora (Slepak Indian tea),Lagynotomus spp. (stink bugs), Leptocorisa oratorius, Leptocorisa varicornis, Lygus spp. (herbal bug), Lygus hesperus (Western herbal bug), Maconellicoccus hirsutus, Neurocolpus longirostris, Nezara viridula (larvae of cotton and vegetable bug (green vegetable bug)), Phytocoris spp. (kanaky), Phytocoris californicus, Phytocoris relativus, Piezodorus guildingi, Poecilocapsus lineatus (bug four-herbal), Psallus vaccinicola, Pseudacysta perseae, Scaptocoris castanea and Triatoma spp. (triatomine bugs: bloodsucking konusheny bugs/kissing bugs), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be used to control insect pests Homoptera (aphids,:, whiteflies, kobylecki). A non-exhaustive list of these pests includes Acrythosiphon pisum (pea aphid), Adelges spp. (Hermes), Aleurodes proletella (cabbage whitefly), Aleurodicus disperses, Aleurothrixus floccosus (woolly whitefly), Aluacaspis spp., Amrasca bigutella bigutella, Aphrophora spp. (kobylecki, cycatki), Aonidiella aurantii (San Jose scale red orange), Aphis spp. (afidi, aphid), Aphis gossypii (aphid bocheva or cotton), Aphis pomi (aphid Codling), Aulacorthum solani (potato aphid common), Bemisia spp. (whitefly), Bemisia argentifolii, Bemisia tabaci (tobacco or cotton whitefly), Brachycolus noxius (Russian wheat aphid), Brachycorynella asparagi (asparagus aphid), Brevennia rehi, Brevicoryne brassicae (cabbage aphid), Ceroplastes spp. (the shield is Cai), Ceroplastes rubens () ruby), Chionaspis spp. (the scales), Chrysomphalus spp. (the scales), Coccus spp. (the scales), Dysaphis plantaginea (Apple aphid pink), Empoasca spp. (Cicada green), Eriosoma lanigerum (aphid Codling blood), Icerya purchasi (mealybug Australian grooved), Idioscopus nitidulus (mango Cicada), Laodelphax striatellus (Cicada dark), Lepidosaphes spp., Macrosiphum spp., Macrosiphum euphorbiae (potato aphid large), Macrosiphum granarium (cereal aphid), Macrosiphum rosae (aphid cut large), Macrosteles quadrilineatus (Cicada), Mahanarva frimbiolata, Metopolophium dirhodum (aphid Rosanna-grass), Mictis longicornis, Myzus persicae (aphid green peach), Nephotettix spp. (fleas leaf rice), Nephotettix cinctipes (Cicada green), Nilaparvata lugens (delvocid brown rice), Parlatoria pergandii (San Jose scale citrus purple), Parlatoria ziziphi (black interior), Peregrinus maidis (Cicada corn), Philaenus spp. (pennisi slobbery), Phylloxera vitifoliae (grape phylloxera leaf), Physokermes piceae (fir) small), Planococcus spp. (mealybugs), Pseudococcus spp. (walochnik or monopolarity), Pseudococcus brevipes (pineapple mealybug), Quadraspidiotus perniciosus (San Jose scale California), Rhapalosiphum spp. (aphid), Rhapalosiphum maida (aphid corn), Rhapalosiphum padi (bird-cherry aphid common), Saissetia spp. (scale, scale), Saissetia oleae () oilseeds or mealybug olive), Schizaphis graminum (cereal aphid common), Sitobion avenae (large grain aphid), Sogatella furcifera (Cicada short-tailed), Therioaphis spp. (warty aphid), Toumeyella spp. (h is rozy), Toxoptera spp. (aphid), Trialeurodes spp. (whitefly), Trialeurodes vaporariorum (greenhouse whitefly), Trialeurodes abutiloneus (whiteflies with striped wings), Unaspis spp. (the scales), Unaspis yanonensis (San Jose scale citrus East) and Zulia entreriana,but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be used to control insect pests Hymenoptera (ants, wasps, and bees). A non-exhaustive list of these pests includes Acromyrrmex spp., Athalia rosae, Atta spp. (umbrella ant or ant-paper), Camponotus spp. (ant-bark beetles), Diprion spp. (sawflies), Formica spp. (the ants), Iridomyrmex humilis (Argentine ant), Monomorium spp., Monomorium minumum (small ant), Monomorium pharaonis (ant pharaohs), Neodiprion spp. (sawflies), Pogonomyrmex spp. (ant-Reaper), Polistes spp. (paper wasp), Solenopsis spp. (fire ant), Tapoinoma sessile (fragrant homemade ant), Tetranomorium spp. (ant sod), hot spp. (OCA ordinary) and Xylocopa spp. (carpenter bees), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be used to control insect pests Isoptcra (termites). A non-exhaustive list of these pests includes Coptotermes spp., Coptotermes curvignathus, Coptotermes frenchii, Coptotermes formosanus (Taiwan yellow-footed termite), Cornitermes spp. (termite soldiers with rostrum), Cryptotermes spp. (gravagne termites), Heteroternes spp. (termites desert), Heterotermes aureus, Kalotermes spp. (gravagne termites), Incistitermes spp. (gravagne the termite, Macrotermes spp. (termite-mushroom), Marginitermes spp. (gravagne the termite, Microcerotermes spp. (termites-the reapers), Microtermes obesi, Procornitermes spp., Reticulitermes spp. (subterranean termite, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes (Eastern subterranean termite), Reticulitermes hageni, Reticulitermes hesperus (Western subterranean termite), Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, Reticulitermes virginicus, Schedorhinotermes spp. and Zootermopsis spp. (wood termites), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be used to control insect pests Lepidoptera - butterflies (modelki and butterflies). A non-exhaustive list of these pests includes Achoea janata, Adoxophyes spp., Adoxophyes orana, Agrotis spp. (scoops), Agrotis ipsilon (scoop-Upsilon), Alabama argillacea (cotton bollworm American), Amorbia cuneana, Amyelosis transitella (navel orangeworm), Anacamptodes defectaria, Anarsia lineatella (mol fruit striped), Anomis sabulifera (jute moth - jute looper), Anticarsia gemmatalis (scoop (velvetbean caterpillar)), Archips argyrospila (fruit-tree tortrix), Archips rosana (tortrix cut Golden), Argyrotaenia spp. (leafroller), Argyrotaenia citrana (tortrix citrus), Autographa gamma, Bonagota cranaodes, Borbo cinnara (Ognevka rice), Bucculatrix thurberiella (moth family Bucculatricidae - cotton leaf perforator), Caloptilia spp. (leaf miners), Capua reticulana, Carposina niponensis (Persico is the first moth), Chilo spp., Chlumetia transversa (cane mol -mango shoot borer), Choristoneura rosaceana (:oblique banded leaf roller), Chrysodeixis spp., Cnaphalocerus medinalis (:grass leafroller), Colias spp., Conpomorpha cramerella, Cossus cossus (butterfly-tree-borer), Crambus spp. (Sasani-Sod webworms), Cydia funebrana (plum moth), Cydia molesta (Oriental moth), Cydia nignicana (pea moth), Cydia pomonella (Codling moth), Darna diducta, Diaphania spp. (stem grinders), Diatraea spp. (moths), Diatraea saccharalis (reed Ognevka), Diatraea graniosella (Ognevka corn southwest), Earias spp. (cotton scoop), Earias insulata (prickly worm scoops), Earias vitella (boxed worm), Ecdytopopha aurantianum, Elasmopalpus lignosellus (Ognevka - lesser cornstalk borer), Epiphysias postruttana (Apple moth light brown), Ephestia spp. (species of moths - flour moths), Ephestia cautella (Ognevka Sukhorukova), Ephestia elutella (Ognevka tobacco), Ephestia kuehniella (Ognevka mill), Epimeces spp., Epinotia aporema, Erionota thrax (banana Tolstoganova), Eupoecilia ambiguella (bertogna grape), Euxoa auxiliaris (caterpillar butterfly-scoops of euxoa), Feltia spp. (the caterpillar of the moth Cutworm Feltia), Gortyna spp. (types of stem grinders), Grapholita molesta (moth Oriental peach), Hedylepta indicata (bean leaf webber), Helicoverpa spp. (Cutworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (boxed worm/cotton bollworm), Heliothis spp. (scoops), Heliothis virescens (scoop tobacco), Hellula undalis (caterpillar the liquidation cabbage), Indarbela spp. (koreeda), Keiferia lycopersicella (tomato leaf miner is ol), Leucinodes orbonalis (Sawfly eggplant), Leucoptera malifoliella, Lithocollectis spp., Lobesia botrana (tortrix moth), Loxagrotis spp. (scoops kind Loxagrotis), Loxagrotis albicosta (scoops kind loxagrotis), Lymantria dispar (Gypsy moth), Lyonetia clerkella (mol leaf-miner), Mahasena corbetti (mesochrysa kind of Mahasena), Malacosoma spp. (econopred ringed), Mamestra brassicae (cabbage scoop), Maruca testulalis (Ognevka kind Maruca), Metisa plana (mesochrysa kind of Metisa), Mythimna unipuncta (caterpillar moths of the genus Mythimna), Neoleucinodes elegantalis (Ognevka), Nymphula depunctalis (pupa or cocoon in a collapsed leaf rice), Operophthera brumata (winter moth), Ostrinia nubilalis (Ognevka corn), Oxydia vesulia, Pandemis cerasana (tortrix normal within), Pandemis heparana (willow of krivosha tortrix), Papilio demodocus, Pectinophora gossypiella (pink boxed cotton worm), Peridroma spp. (scoops), Peridroma saucia (scoop margaritova), Perileucoptera coffeella (dominating mol), Phthorimaea operculella (mol potato tuber), Phyllocnisitis citrella, Phyllonorycter spp. (mining moths), Pieris rapae (caterpillar of rupnica), Plathypena scabra, Plodia interpunctella (South barn Ognevka), Plutella xylostella (Diamondback moth), Polychrosis viteana (moth vine), Prays endocarpa, Prays oleae (oilseeds mol), Pseudaletia spp. (scoops), Pseudaletia unipunctata (scoop meadow), Pseudoplusia includens (moth), Rachiplusia nu, Scirpophaga incertulas, Sesamia spp. (stem grinders), Sesamia inferens (pink stem borer), Sesamia nonagrioides, Setora nitens, Sitotroga cerealella (mol barley or grain), Sparganothis pilleriana, Spodoptera spp. (scoops), Spodoptera exigua (beet the ranks scoop), Spodoptera frugiperda (scoop herbal), Spodoptera oridania (South scoop), Synanthedon spp. (koreeda, Steklyannyy), Thecla basilides, Thermisia gemmatalis, Tineola bisselliella (mol bedroom, furniture), Trichoplusia ni (scoop), Tuta absoluta, Yponomeuta spp., Zeuzera coffeae (moth Mino-Mushi) and Zeuzera pyrina (moth corrosive), but is not limited to this.

In one embodiment, the invention disclosed in this document can be used to control insect pestsMallophaga(ect., hematophagous biting, proedi). A non-exhaustive list of these pests includes Bovicola ovis (flashed sheep), Menacanthus stramineus (pogoed dvuhmetrovy chicken) and Menopon gallinea (pogoed pale chicken), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be applied to control insect pestsOrthoptera- orthopteroidea jumping Orthoptera (grasshoppers, locusts, elephant shrews, locusts and crickets). A non-exhaustive list of these pests includes Anabrus simplex (large dark wingless green grasshopper), Gryllotalpidae (mole crickets), Locusta migratoria, Melanoplus spp. (locusts), Microcentrum retinerve (grasshopper pocrisy), Pterophylla spp. (grasshoppers), chistocerca gregaria, Scudderia furcata (Sabine's grasshopper) and Valanga nigricorni,but is not limited to this.

In another embodiment, the invention disclosed in this document can be applied to combat what becomemy pests Phthiraptera(lice). A non-exhaustive list of these pests includes Haematopinus spp. (lice of the genus of blood-sucking large and small ruminants and pigs), Linognathus ovillus (sheep louse), Pediculus humanus capitis (the head louse), Pediculus humanus humanus (head lice a) and Pthirus pubis (pubic louse), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be applied to control insect pestsSiphonaptera(fleas). A non-exhaustive list of these pests includes Ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea) and Pulex irritans (human flea), but is not limited to this.

In another embodiment, the invention disclosed in this document can be applied to control insect pestsThysanoptera(bajracharya, Puzanova, thrips). A non-exhaustive list of these pests includes Frankliniella fusca (tobacco thrips), Frankliniella occidentalis (Western flower thrips), Frankliniella shultzei Frankliniella williamsi (corn trips), Heliothrips haemorrhaidalis (greenhouse thrips), Riphiphorothrips cruentatus, Scirtothrips spp., Scirtothrips citri (citrus thrips), Scirtothrips dorsalis (thrips, yellow tea), Taeniothrips rhopalantennalis and Thrips spp.,but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be applied to control insect pests is Thysanura (Seinajoki). A non-exhaustive list of these pests includes Lepisma spp. (Chechulina) and Thermobia spp. (thermobia), but is not limited to this.

In another embodiment, the invention disclosed in this document can be applied to control insect pestsAcarina(ticks and mites). A non-exhaustive list of these pests includes Acarapsis woodi (tracheal mite of honey bees), Acarus spp. (tyroglyphidae (barn, bread) ticks), Acarus siro (grain mite), Aceria mangiferae (mango clasic), Aculops spp., Aculops lycopersici (rusty tomato mite), Aculops pelekasi, Aculus pelekassi, Aculus schlechtendali (Apple brown tick), Amblyomma americanum (tick-tick Lone Star), Boophilus spp. (mites), Brevipalpus obovatus (greenhouse red mite), Brevipalpus phoenicis (mite-plasmatica), Demodex spp. (cestocide mites of the genus Demodex), Dermacentor spp. (pliers with hard cover kind of Dermacentor), Dermacentor variabilis (Ixodes tick dog changeable), Dermatophagoides pteronyssinus (house dust mite), Eotetranycus spp., Eotetranychus carpini (yellow hornbeam spider mite), Epitimerus spp., Eriophyes spp., Ixodes spp. (mites kind Ixodes), Metatetranycus spp., Notoedres cati, Oligonychus spp., Oligonychus coffee, Oligonychus ilicus (clasic spider South), Panonychus spp., Panonychus citri (citrus red mite), Panonychus ulmi (mite red fruit), Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemun latus (greenhouse transparent mite), Rhipicephalus sanguineus (brown dog tick), Rhizoglyphus spp. (ticks root), Sarcoptes scabiei (classesthey, Sudan itch), Tegolophus perseaflorae, Tetranychus spp., Tetranychus urticae (common spider mite and Varroa destructor (parasitic varroatosis mite of honey bees of the genus, Varroa), but is not limited to this.

In yet another embodiment, the invention disclosed in this document can be applied to control insect pestsNematoda(nematodes - type perichromatin worms). A non-exhaustive list of these pests includes Aphelenchoides spp. (parasitic leaf and Bud nematodes softwood), Belonolaimus spp. (sting nematode), Criconemella spp. (ringed nematodes), Dirofilaria immitis (heart worm in dogs), Ditylenchus spp. (stem and bulb nematode), Heterodera spp. (cyst nematodes), Heterodera zeae (corn cyst nematode), Hirschmanniella spp. (root nematodes), Hoplolaimus spp. (nematodes-lanzetti), Meloidogyne spp. (nodule nematodes), Meloidogyne incognita (pea incognita nematode), Onchocerca volvulus (parasitic worm with steeply curved tail, which causes onchocerciasis), Pratylenchus spp. (root nematodes of the genus Pratylenchus), Radopholus spp. (earth nematodes) and Rotylenchus reniformis (reniform nematode), but is not limited to this.

In another embodiment, the invention disclosed in this document can be applied to control insect pests of the classSimfile(symphylans). A non-exhaustive list of these insects-pest which includes millipedes Scutigerella immaculate, but is not limited to this.

More detailed information can be found in the directory: Arnold Mallis "Handbook of Pest Control - The Behavior, Life History, and Control of Household Pests", 9th edition, publishing law GIE Media Inc. (2004).

MIXTURE

The invention disclosed in this document, can also be applied in conjunction with various insecticides, how to save, and in order to obtain synergy. Such insecticides include antibiotic insecticide, insecticides based on macrocyclic lactone (for example, avermectin insecticides, milbemycin insecticides, and spinningovye insecticides), containing arsenic insecticides, insecticides of plant origin, urethane insecticides (for example, benzofuranyl-methylcarbamate insecticides, dimethyl-urethane insecticides, oxime-urethane insecticides, and phenyl-methyl-urethane insecticides), diamide insecticides, desiccants insecticides, dinitro-phenol insecticides, fluorine-containing insecticides, formamidine insecticides, fumigant insecticides, inorganic insecticides, regulators of insect development (e.g., chitin synthesis inhibitors, juvenile hormone analogues, juvenile hormones, the molting hormone agonists, hormones molt, molting inhibitors, prikazani, and other unclassified regulators of insect development), the insecticides on the Snov analogues nereistoxin, similar insecticides,nicotinoid insecticides (for example, nitroguanidine insecticides, nitromethylene insecticides, and pyridylmethylamine insecticides), organochlorine insecticides, organophosphorus insecticides, oxadiazine insecticides, oxadiazole-containing insecticides, phthalimide insecticides, pyrazol insecticides, PYRETHROID insecticides, aminopyrimidine insecticides, pyrrole-containing insecticides, insecticide-based Ternovoi acid insecticides on the basis of tetronic acids, titlovi insecticides, thiazolidinone insecticides, tiomochevinoi insecticides, mcevenue insecticides, and other unclassified insecticides, but not ogranichivayutsya it.

Some of the specific insecticides, which can be beneficial (benefit) applied in combination with the invention disclosed in this document, include the following: 1,2-dichloropropane, 1,3-dichloropropene, abamectin, Arafat, acetamiprid, action, acetarsol, acrinathrin, Acrylonitrile, alankar, aldicarb, aldoxycarb, Aldrin, allethrin, Allesley, allistar, alpha-cypermethrin, alpha-endosulfan, amidation, aminocarb, Amiton, amitraz, anabasine, amidation, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, attout, barium fluorosilicate preparation, Bartin, bendiocarb, benfuracarb, bensultap, be the a-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioeconomical, bioprotein, bioresmethrin, bistriflate, borax, boric acid, orthoboric acid, pumpevents, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bofenkamp, buprofezin, betacar, butamifos, butocarboxim, Boutonnat, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanilate, carbaryl, carbofuran, carbondisulfide, carbontetrachloride, carbophenothion, carbosulfan, cartap, chlorantraniliprole, chlorobicyclo, chlordane, Chlordecone Chlordimeform, chlorethoxyfos, chlorfenapyr, chlorfenvinfos, chlorfluazuron, chlormephos, chloroform, chlorpicrin, chlorphoxim, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, resmethrin, cloethocarb, closantel, clothianidin, acetoarsenite copper, copper arsenate, copper naphthenate, copper oleate, coumaphos, comitat, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, zantout, centrailia, cyclotron, cicloprofen, cyfluthrin, cigalotrin, cypermethrin, cyphenothrin, cyromazine, cetiat, DDT, carbofuran, deltamethrin, deletion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulfone, diafenthiuron, dialifos, diatomaceous earth diazinon, deception, dichlofenthion, dichlorvos, dicresyl, dicrotophos, di is clonil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, demean, dimethoat, demetrin, dimethylene, dimetilan, Dinex, dynapro, dinoseb, dinotefuran, giovanola, dioxybenzone, dioxane, dioxathion, disulfoton, deticates,dlemon, dinitro-o-cresol, doramectin, ecdysterone, emamectin, EMPC, empenthrin, endosulfan, endation, endrin, the entomopathogenic nematode (EPN), epitonin, eprinomectin, esfenvalerate, Etats, ethiofencarb, ation, amiprol, etoac-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, ethylxanthate-disulfide (EXD), famphur, fenamiphos, pensator, fenchlorphos, fanmakers, fenfluthrin, fenitrothion, fenobucarb, tenoxicam, fenoxycarb, generatin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid, flubendiamide, flucturion, flucycloxuron, flucythrinate, lufenuron, flufenoxuron, flavandiols, fluvalinate, fonofos, formetanate, formation, formparent, tomatlan, pospert, hostican, furathiocarb, pyrethrin, gamma cigalotrin, gamma-HCH, halftracks, halogenated, hexachlorocyclohexane (HCH), HEOD, heptachlor, heptenophos, heteropus, hexaflumuron, Aldrin (HHDN), hydramethylnon, hydrogen cyanide (hydrocyanic acid), hydroprene, chiquisca, Imidacloprid, imiprothrin, indoxacarb logmean, IPSP for acquiring, isazofos, isobenzan, ISOC rbots, Isodrin, isofenphos, isoprocarb, isoprothiolane, isocial, isoxathion, ivermectin, jasmolin I, jasmolin II, idents, juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan, CANopen, lambda cigalotrin, arsenate of lead, leemartin, leptophos, lindane, liempo, lufenuron, litigation, Malathion, malaanonan, masimax, mecarbam, macartan, Manson, mephosfolan, mercury chloride, resolvents, metaflumizone, methacrifos, metamidophos, mitigation, methiocarb, Metacritic, methomyl, methoprene, Methoxychlor, methoxyfenozide, methyl bromide, methyl chloroform, methylene chloride, metofluthrin, metolcarb, methoxamine, mevinphos, mexacarbate, milbemectin, milbemycin-oxime, metafox, mirex monocrotophos, porpotion, moxidectin, naftalis, naled, naphthalene, nicotine, diflouride, nitenpyram, nithiazine, nitrilases, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxidation, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, enflurane, pentachlorophenol, permethrin, phenkapton, phenothrin, pentat, Fort, fozalon, phosfolan, phosmet, fossiler, phosphamidon, phosphine, phoxim, facsim-methyl, perimeters, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, dichlordifenyltrichlormetylmethane (pp'-DDT), prallethrin, precoce I, precoce II, precoce III, presidios, profenofos, perflutren, bromacil, Promega is b, propafol, propetamphos, propoxur, protection, prothiofos, procoat, protrudent, pyraclofos, perflubron, pyrazophos, prismatron, pyrethrin I, pyrethrin II, pyridaben, pyridalyl, predatation, pyriphlegethon, pyrimidifen, perimeter, periphral, pyriproxifen, quassia, finalpos, finalpos-methyl, gination, rafoxanide, resmethrin, rotenon, reaney, sabadilla, schradan, selamectin, selflove, silica gel, sodium arsenite, sodium fluoride, sodium fluorosilicate preparation, sodium thiocyanate, sofabed, spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron, surfacefor, sulfluramid, sulfotep, Sulfuryl-fluoride, sulprofos, Tau-fluvalinate, Casimir, tetrachloroferrate (TDE), tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, tetraethylpyrophosphate (TEPP), tarletan, terbufos, tetrachlorethane, tetrachlorvinphos, tetramethrin, theta-cypermethrin, thiacloprid, thiamethoxam, micropos, dicarboxy, thiocyclam, thiodicarb, thiofanox, thiometon, thiosulfat, thuringiensis, toppenberg, tralomethrin, transfluthrin, transpermethrin, triuralin, triazamate, triazophos, trichlorfon, trichlormethane-3, trichloronat, tritanopes, triflumuron, trimeter, triplen, validation, unilibro, XMC, killchar, Zeta-cypermethrin, sulprofos, and alpha-action, but are not limited to this.

In addition, can be applied to any combination what s the above-mentioned insecticides.

The invention disclosed in this document, can also be applied, in order to achieve savings and synergies, together with acaricides, algaecides, antifeedants, avicide, bactericides, means to deter birds, chemosterilants, fungicide, antidotes for herbicides, herbicides, baits for insects, means to deter insects (repellents), means to deter mammals, tools dysfunction mating, molluscicides, activators defense reactions of plants, regulators of plant development, rodenticides, synergists, defoliants, drying means (dessicate), disinfectants, chemical signal substances, and viruscode (these categories are not necessarily mutually exclusive).

For more information you can refer to the "Compendium of Pesticide Common Names", posted on the website:http://www.alanwood.net/pesticides/index.html.You can also refer to the Handbook: "The Pesticide Manual" 14th Edition, edited by C D S Tomlin, publishing law 2006 - British Crop Production Council.

SYNERGISTIC MIXTURES

The invention disclosed in this document can be applied in conjunction with other compounds, such as compounds mentioned in the section "Mixture", obtaining a synergistic mixtures, where the mechanism (method) steps is joining in mixtures is similar, similar, or different.

Examples of mechanism of action include: acetylcholinesterase inhibitor; sodium channel modulator; an inhibitor of chitin biosynthesis; antagonist of GABA-dependent chloride channels; antagonist of GABA - and glutamate-dependent chloride channels; acetylcholine receptor agonist; an inhibitor of MET I; inhibitor Mg-stimulated ATPase (adenosinetriphosphatase); nicotinic acetylcholine receptor; disrupter membranes mid-gut of the insect; the breaker of oxidative phosphorylation and receptor ryanodine (RyRs), but is not limited to this.

In addition, the following connections: piperonyl-piperonyl, pipracil, Propolisum, sesamex, sesamolin and sulfoxide, known as synergists and can be used together with the compound of the invention disclosed in this document.

COMPOUNDS

Pesticide rarely suitable for use in its pure form. Usually it is necessary to add other substances so that the pesticide can be used in the required concentration and in an acceptable form, making it easy to apply, manipulate, transport, and store the pesticide and to obtain maximum activity of the pesticide. Thus, pesticides are mixed with obtaining, for example, lures, concentrated emulsions, powdered drugs, emulsifiable concentrates, fumigants, Geel is th, granules, microencapsulating preparations for seed, suspension concentrates, suspoemulsions, tablets, water-soluble liquid, dispersible in water granules or bulk drugs, wettable powders, and ultra-low volume solutions.

For more information on the types of trains, consult the catalogue "Catalogue of Pesticide Formulation Types and International Coding System" Technical monograph No.2, 5th edition, CropLife International (2002).

Pesticides used most frequently in the form of aqueous suspensions or emulsions prepared from concentrated formulations of these pesticides. Such water-soluble, suspendiruemye in water or emulsifiable formulations are either solids, usually known as wettable powders, or dispersible in water, granules, or liquids, usually known as emulsifiable concentrates or aqueous suspension. Wettable powders, which can be pressed with getting dispersible in water, the granules include a homogeneous mixture of the pesticide carrier, and surfactants. The concentration of the pesticide is typically from about 10% to about 90% wt.. the Media is usually chosen from among attapulgite clays, montmorillonite clays, diatomaceous earths, or purified silicates. Effective surfactants, with ergasias in the amount of from about 0.5% to about 10% relative to the wettable powder, find out the number from sulphonated lignins, the condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulphates, and nonionic surfactants, such as ethyleneoxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides have appropriate concentration of the pesticide, such as from about 50 to about 500 grams per liter of liquid, which is dissolved in the carrier, representing either miscible with water, the solvent or mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatic substances, in particular xylenes and oils, especially high-boiling naphthalene and olefinic portions of petroleum such as heavy naphtha, enriched in aromatic compounds. Can also be used in other organic solvents, such as terpene solvents, including derivatives of rosin, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from suitable anionic and nonionic surfactants.

Aqueous suspensions include suspensions of water-insoluble pesticides dispersed in an aqueous medium in a concentration in the range of the region from approximately 5% to approximately 50 wt.%. Suspensions are prepared by finely grinding pesticide and energetic blend it in a medium consisting of water and surfactants. Ingredients such as inorganic salts and synthetic or natural gums, can also be added to increase the density and viscosity of aqueous media. Often the most effective is the simultaneous grinding and mixing of the pesticide through preparation of an aqueous mixture and homogenization her in a device such as a sand mill, ball mill, or a homogenizer parsepage type.

Pesticides can also be applied in the form of granular compositions that are particularly useful for application to the soil. Granular compositions typically contain from about 0.5% to about 10% wt. pesticide dispersed in the carrier, which includes clay or a similar substance. Such compositions are typically prepared by dissolving the pesticide in a suitable solvent and by applying it to a granular carrier which has been pre-formed with an appropriate particle size in the range from about 0.5 to about 3 mm, Such compositions can also be prepared by producing a dense mass or paste of the carrier and connections and by rough grinding and drying of gaining the m desired size of the granular particles.

Powdered preparations containing pesticide, prepared by thorough mixing of the pesticide in powdered form with a suitable dust from agricultural carrier, such as kaolin clay, crushed volcanic rock, and the like. Powdered drugs appropriately can contain from about 1% to about 10% of the pesticide. They can be applied in the form of a preparation for disinfection of seeds or in the form of the drug for foliar feeding through the machine-afiliates.

As is practical application of the pesticide in the form of a solution in an appropriate organic solvent, usually in mineral oil, such as insecticide (aerosol) oils, which are widely used in chemistry.

Pesticides can also be applied in the form of aerosol compositions. In such compositions the pesticide is dissolved or dispersed in the carrier, which is creating pressure mixture of propellants. Aerosol composition packaged in a container-the container from which the mixture is distributed through dispenser-dispenser.

Pesticide baits get in the case when the pesticide is mixed with food or attractant, or with both. In the case when insects eat the bait, they also consume and pectic the D. Bait can be in the form of granules, gels, granular powders, liquids, or solids. They are used in areas where insects pests.

The fumigants are pesticides that have a relatively high vapor pressure and, therefore, can be in the form of gas in concentrations sufficient to kill pests in the soil or in enclosed/confined spaces. The toxicity of the fumigant is proportional to its concentration and time of exposure. They are characterized by good diffusion and act by penetration into the respiratory system of insects or by absorption through the cuticle of the insect pests. The fumigants used to control insect pests from products stored in gas-tight cloths in sealed rooms or in rooms or in special chambers.

Pesticides can be microencapsulated by suspension of the particles or droplets of pesticide in reservoir-polymers of various types. By changing the chemistry of the polymer or by changing factors in processing technology, can be formed of microcapsules with different sizes, solubility, wall thickness, and degree of permeability. These factors determine the speed with which the active ingredient is released under NR is three, which, in turn, affects subsequent residual action, speed of action, and the smell of the product.

Concentrates oil solutions make by dissolving the pesticide in the solvent, which will keep the pesticide in solution. Oil solutions of pesticide usually provide more rapid knockdown effect and mortality of insect pests than other formulations due to the solvents which themselves possess pesticidal action, and vsledstvii dissolution of the wax shell outer cover, which increases the capture rate of the pesticide. Other advantages of oil solutions include better storage stability, better penetration into the gaps/veinlets, and better adhesion to oily surfaces.

Another embodiment is an emulsion of oil-in-water, which emulsion contains oil globules, each of which is provided with a shell-based lamellar liquid crystal and dispersed in the aqueous phase, where each oil globule contains at least one compound, which is active from the point of view of agriculture, and is separately covered monolinolenin or oligomineral layer, includes: (1) at least one lipophilic nonionic surfactant, (2) at least one nonionic hydrophilic the surfactant and (3) at least one ionic surfactant, where the globules have an average particle diameter equal to less than 800 nanometers. Additional information version implementation disclosed in patent publications: U.S. patent publication 20070027034, published on 1 February 2007, having a serial number of the patent application 11/495228. For ease of use, this option will be referred to as "OIWE = emulsion, oil-in-water".

For more information, please refer to the manual "Insect Pest Management" 2nd edition, D. Dent, publishing the right CAB International (2000). In addition, for more detailed information, refer to the Handbook Arnold Mallis "Handbook of Pest Control - The Behavior, Life History, and Control of Household Pest" 9th edition, publishing law GIE Media Inc. (2004).

OTHER COMPONENTS of the COMPOSITIONS

As a rule, in the case when the invention disclosed in this document, is used in the composition, such a composition may also contain other components. These components include (this is a non-exhaustive list vzaimoisklyuchayushiye (complementary or compatible) components) wetting agents, fillers, adhesive fillers, penetrants, buffer substances, complexing/binder reagents that reduce the offset, substances that increase compatibility of components, prativasinau the e reagents, brightening/detergents, and emulsifiers, but are not limited to this. Several of the components described immediately below.

Wetting agent is a substance which when added to liquid increases the distribution or the ability of the liquid by reducing the interfacial tension on the border between the fluid and the surface on which it is distributed. Wetting agents used in agricultural formulations to achieve two basic functions: during processing and manufacturing to increase the speed of wetting of powders in water to produce concentrates for soluble liquids or concentrated suspensions; and during the mixing of the product with water in the tank of the spray to reduce wetting wettable powders and to improve the penetration of water dispersible granules in water. Examples of the wetting agents used in the formulations based on wettable powders, concentrates, suspensions, dispersible in water, the granules are: sodium lauryl sulfate; dioctyl-sulfosuccinate sodium; apes; and aliphatic alcohols ethoxylates.

Dispersing reagent is a substance that is adsorbed on the surface of particles and contributes to the conservation of the state of dispersion of the particles and prevent reset their neogregarine. Dispersing the reagents of the type used in agriculture compositions to facilitate the formation of a dispersion and suspension at the time of manufacture, and to guarantee the re-formation of a dispersion in water in the tank of the spray. They are widely used in wettable powders, concentrates, suspensions and dispersible in water, the granules. Surfactants, which are used as dispersing agents have the ability to strongly adsorb on the surface of the particles and to provide a barrier charge or spatial barrier to reaggregate particles. The most commonly used surfactants are anionic, nonionic substances, or a mixture of two types of surfactants. For compositions on the basis of the wettable powders, the most commonly used dispersing reagents are sodium lignosulfonate. As for concentrated suspensions, very good adsorption and stabilization is obtained using polyelectrolytes, such as condensates of formaldehyde and naphthalenesulfonic sodium. Also use tridirectional-ethoxylate esters of phosphoric acid. Nonionic compounds such as alkylenediamine condensates and copolymers of ethylene oxide-propylene oxide, sometimes combined the with anionic compounds as dispersing reagents for concentrated suspensions. In recent years, as a dispersing reagents have been developed new types of polymeric surfactants with very high molecular weight. They have a very long hydrophobic 'main chain' and a large number of ethyleneoxide chains forming 'teeth' 'comb-like' surface-active substances. These polymers with high molecular weight can give a very good long-term stability of the concentrated suspensions, because the hydrophobic main chain have many anchor points mechanical fixation on the surfaces of the particles. Examples of the dispersing agents used in compositions for agriculture are: sodium lignosulfonate; condensates of formaldehyde and naphthalenesulfonic sodium; tridirectional-ethoxylate esters of phosphoric acid; aliphatic alcohols ethoxylates; alkyl ethoxylates; block copolymers of ethylene oxide-propylene oxide; and grafted copolymers.

Emulsifying agent is a substance which stabilizes the suspension droplet of the liquid phase into another liquid phase. Without emulsifying reagent two liquid could be separated into two immiscible liquid phases. The most commonly used mixture of emulsifiers include alkyl phenol or aliphatic alcohol with twelve or more ethylenoxide links and malarstwo the th calcium salt of dodecylbenzenesulfonate. The range of values hydrophilic-lipophilic balance ("HBL") from 8 to 18 will usually provide a good stable emulsion. The stability of the emulsion can sometimes be improved by adding small amounts of surfactants on the basis of blockcopolymers of ethylene oxide-propylene oxide (EO-PO).

Solubilizers substance is a surfactant that will form micelles in water at concentrations above the critical concentration of micelles. Then micelles can dissolve or solubilisate water-insoluble substances inside the hydrophobic part of the micelle. The type of surfactants commonly used to solubilize comprise nonionic substances: sorbitan-monooleate; ethoxylates of sorbitan-monooleate; and metrolite esters.

Surfactants are sometimes used, either as such or together with other additives, such as mineral or vegetable oils as adjuvants, which are injected into the reservoir of the spray mixture to enhance the biological effects of the pesticide on the target. The types of surfactants used for the effect of biological amplification, as a rule, depend on the nature and mechanism of action of the pesticide. However, often they are Sobolinaya substances, such as: alkylalkoxysilane; ethoxylates of linear aliphatic alcohols, ethoxylates of aliphatic amines.

The carrier or diluent in the composition used in agriculture, is a substance added to a pesticide to obtain a product with desired strength. Typically, the carriers are substances with a high absorbent capacity, while thinners are usually substances with a low absorbent capacity. Carriers and diluents used in the composition of the powdered drugs, wettable powders, dispersible granules and granules in water.

Organic solvents are mainly used in the composition of emulsifiable concentrates, preparations ULV (Ultrabay volume), and to a lesser extent in the composition of the granular preparations. Sometimes use a mixture of solvents. The first major group of solvents are aliphatic paraffin oil, such as kerosene or purified paraffins. The second main and most commonly used group includes aromatic solvents such as xylene and fractions with higher molecular weight, comprising C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as co-solvents to prevent crystallization of pesticides in the emulsification of the composition in water. Alcohols and sometimes the use as co-solvents to enhance the dissolving ability.

Thickeners or gelling reagents are mainly used in the composition of concentrated suspensions, emulsions, and suspoemulsions for modifying rheological properties and fluidity of the liquid and to prevent the separation and deposition of the dispersed particles or droplets. Thickening, gelling, and protivovazdushna reagents generally fall into two categories, namely, water-insoluble solid particles and water-soluble polymers. It is possible to obtain compositions on the basis of concentrated suspensions using clays and silicas. Examples of these types of materials include montmorillonite, for example, bentonite; magnesium aluminosilicate; and attapulgite, but are not limited to this. For many years as a thickening agent-gelling reagents used water-soluble polysaccharides. The most commonly used types of polysaccharides are extracts of seeds and seaweed or are synthetic derivatives of cellulose. Examples of these types of substances include guar gum; gum beans carob; carrageenan; alginates; methylcellulose; carboxymethylcellulose sodium (SCMC); hydroxyethyl cellulose (HEC), but is not limited to this. Other types protivovazdushna reagents based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. the school one good protivootecnami reagent is xanthan gum.

Microorganisms causing damage made products. Therefore, to eliminate or reduce their effects using preservative chemicals. Examples of such reagents include propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; sodium saltpair-hydroxybenzoic acid; methylpair-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT), but is not limited to this.

The presence of surfactants, which reduce the interfacial tension, often causes foaming compositions based on water during mixing operations when receiving and when applied by means of a reservoir of the dispenser. In order to reduce the tendency to foam, either during the preparation stage, either before pouring into bottles often add protivovspenivayushchie reagents. Usually, there are two types protivovspenivayushchie reagents, namely, silicone compounds and asilicone connection. Silicone compounds are usually a water emulsion of dimethylpolysiloxane, while asilicone protivovspenivayushchie reagents are water-insoluble oils, such as octanol and nonanol, or silicon dioxide. In both cases, the function protivovspenivayushchie reagent is to wipe the surface of the but-active substances with the interface air-water.

Additional information can be found in the book "Chemistry and Technology of Agrochemical Formulations", edited by D. A. Knowles, publishing law Kluwer Academic Publishers (1998). You can also refer to the overview A. S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry "Insecticides in Agriculture and Environment - Retrospects and Prospects" publishing law Springer-Verlag (1998).

APPLICATIONS

The actual amount of pesticide that must be applied to the locus (location) insect pests, as a rule, is not critical and can easily be determined by experts in the field. In General, I believe that concentrations of from about 0.01 gram of pesticide per hectare to about 5000 grams of pesticide per hectare provide good pest control.

The locus to which is applied the pesticide, can be any locus habitat of the insect pest, for example, vegetable crops, fruit and nut trees, grape vines, ornamental plants, Pets, internal or external surfaces of buildings, and the soil around buildings. To control insect pests, usually means that the locus reduce populations of insect pests, their activity, or both. This can occur when: insect pests are being expelled from the locus; when insect pests 'take down' in Utri locus or around it; or when insect pests destroy, in whole or in part, in or around the locus. Of course, you may have a combination of these results. Typically, populations of insect pests, their activity, or both, preferably reduced by more than fifty percent, preferably more than 90 percent.

Typically, when using lures, baits are placed on the surface of the earth in that place, where, for example, termites can enter into contact with the bait. Baits can also be applied to the surface of the premises, (horizontal, vertical, or inclined surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with the bait.

Due to the unique ability of the eggs of some insects to be resistant to pesticides, to fight with the newly emerged larvae may be desirable to re-application of pesticides.

Systemic movement of pesticides in plants can be used to control insect pests on one part of a plant by applying a pesticide to another part of the plant. For example, struggle with eating foliage insects can be controlled by drip irrigation or application of pesticides on the bottom of the grooves, or by treatment of seeds before sowing. Seed treatment may be the use of the Jena to all types of seeds, including the seeds that will germinate plants genetically modified with obtaining ekspressirovali characteristic of adaptation to certain conditions. Representative examples include seeds expressing proteins toxic to invertebrate pests, such asBacillus thuringiensisor other insecticidal toxins, seeds expressing herbicide resistance, such as seeds "Roundup Ready" varieties of seeds, allowing the spraying of the herbicide Roundup during the vegetation period), or seeds with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, increased nutritional value, or any other beneficial traits. In addition, such seed treatment compound (composition) of the invention disclosed in this document, can further enhance the ability of plants to better withstand hard/stressful growing conditions. This leads to a healthier, stronger plant that may give higher yields in the period of harvest.

Clearly evident that the invention can be applied to plants genetically modified with obtaining ekspressirovali characteristic of adaptation to certain conditions, such asBacillus thuringiensisis there other insecticidal toxins, or on plants expressing herbicide resistance, or plants with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, increased nutritional value, or any other beneficial traits.

The invention disclosed in this document, suitable for combating endoparasites and ectoparasites in the veterinary sector medical care or in the field of animal welfare. Compounds used in a known manner, e.g. by oral administration in the form of, for example, tablets, capsules, drinks, granules, by means of surface coating in the form of, for example, dipping, spraying, pouring, spot/local deposition, or spraying/dusting, and by parenteral administration in the form of, for example, injection.

The invention disclosed in this document, can also be applied mainly in the content of livestock, for example, in the contents of large and small cattle, sheep, pigs, chickens, and geese. Suitable formulations administered orally to the animals with drinking water or with food. Dosages and formulations that are appropriate depend on the type of animal.

Before a pesticide can be used or sold in large quantities, such a pesticide subject to a long process of evaluation of different public authorities(local, regional, state, national, international). Numerous data requirements precisely defined regulatory authorities and should be considered when data is received and when applying the registrant of the product or any other representative on behalf of the registrant of the product. These government authorities then review such data and, if come to a conclusion about the definition of security, then give the potential consumer or the seller's permission to register the product. Then, in the locality where provided and supported check product, the consumer or the seller may use or sell such pesticide.

Headings and captions in this document are given only for convenience and should not be used for interpretation of any of its parts.

Table 1
No.StructureInfrared spectroscopy (cm-1)Mass spectrometryMelting point (°C)1H NMR (CDCl3, δ)1
2 551,1 (M-H)108-1248,55 (s, 1H), 8,15 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.0 Hz, 2H), 7,55 (d, J=8.7 Hz, 2H), 7,39 (d, J=8.7 Hz, 2H), 6.90 to (s, 1H), 5,17 (DD, J=9,5, 3,4 Hz, 1H), 4,73 (d, J=1.9 Hz, 1H), 3,79-3,62 (m, 2H), 3,51 (, 3H), 3,49 (s, 3H), 3,39 (s, 3H), of 3.28 (t, J=9.4 Hz, 1H), 1,35 (d, J=6.3 Hz, 3H)
4459 (M-H)151-1558,54 (s, 1H), 8,14 (d, J=8.5 Hz, 2H), 7,79 (d, J=8,9 Hz, 2H), 7,55-of 7.48 (m, 2H), 7,37 (d, J=8.5 Hz, 2H), 6,77-of 6.73 (m, 1H), 2,18 was 1.06 (m, 10H), 1,00-of 0.93 (m, 3H)
5449 (M-H)136-1388,53 (s, 1H), 8,12 (d, J=7.9 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,46 (d, J=8,9 Hz, 2H), 7,37 (d, J=9.1 Hz, 2H), 6,70 (s, 1H)and 3.59 (s, 2H), 3,42 (s, 3H), and 1.54 (s, 6H)

6447 (M-H)161-1648,53 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9,2 Hz, 2H), 7,47 (d, J=8,3 Hz, 2H), 7,37 (d, J=8,9 Hz, 2H), is 6.61 (s, 1H), 1,84-to 1.77 (m, 2H)and 1.51 (s, 6H), 1,46-of 1.32 (m, 2H), of 0.95 (t, J=7,3 Hz, 3H)
7 3334, 1758, 1740, 1725, 1616, 1517590 (M+H), 588 (M-H)-at 8.60 (s, 1H), 8,16 (s, 1H), with 8.05 (d, J=9.1 Hz, 2H), to 7.77 (d, J=9.1 Hz, 2H), EUR 7.57 (d, J=9.0 Hz, 2H), 7,35 (d, J=8,9 Hz, 2H), of 5.81 (s, 1H), 4,37 (kV, J=7,1 Hz, 2H), USD 1.43 (s, 6H), to 1.37 (t, J=7,1 Hz, 3H)
8473 (M-H)170 - 1738,54 (s, 1H), 8,15 (d, J=8.5 Hz, 2H), 7,79 (d, J=9.1 Hz, 2H), of 7.48 (d, J=8,4 Hz, 2H), 7,37 (d, J=8,9 Hz, 2H), 6,80 (width, 1H), 1,78 (s, 6H)
10457 (M+H)203-2078,55 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.0 Hz, 2H), 7,50 (d, J=8,8 Hz, 2H), 7,39 (d, J=8,9 Hz, 2H), 6,65 (s, 1H), 5.17 to to 4.92 (m, 1H), 1,32 (d, J=6.3 Hz, 6H)

17479 (M+H)88-908,55 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.5 Hz, 2H), 7,38 (d, J=8,3 Hz, 2H), 6.87 in (s, 1H), 5,41-to 5.21 (m, 1H), 4.16 the (square d, J=7,1, 1.2 Hz, 2H), 2,71 (DD, J=15,4, 7.5 Hz, 1H), to 2.57 (DD, J=15,4, 5.6 Hz, 1H), 1,39 (d, J=6.3 G is, 3H), of 1.26 (t, J=7,1 Hz, 3H)
18495 (M+H), 493 (M-H)72-758,54 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,79 (d, J=8,9 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H), 7,38 (d, J=8.6 Hz, 2H), 6,79 (s, 1H), 3,69 (DD, J=5,5, 3,9 Hz, 2H), 3,68 (s, 2H), of 3.56 (DD, J=5,8, 3.5 Hz, 2H), 3,37 (, 3H), and 1.54 (s, 6H)
19433 (M+H), 431 (M-H)163-1658,53 (s, 1H), 8,10 (d, J=8.6 Hz, 2H), to 7.77 (d, J=8,9 Hz, 2H), of 7.48 (d, J=8.5 Hz, 2H), was 7.36 (d, J=8.6 Hz, 2H), 6,77 (s, 1H), 6,18 (DD, J=17,5, up 10.9 Hz, 1H), 5,23 (d, J=17.5 Hz, 1H), 5,13 (d, J=10,9 Hz, 1H), of 1.59 (s, 6H)

20479 (M+H), 477 (M-H)151-1548,54 (s, 1H), 8,12 (d, J=8.5 Hz, 2H), 7,78 (d, J=8,9 Hz, 2H), of 7.48 (d, J=8.5 Hz, 2H), 7,37 (d, J=8.6 Hz, 2H), 6.89 in (s, 1H), 4,25 (kV, J=7.2 Hz, 2H), 1,64 (s, 6H), of 1.28 (t, J=7,1 Hz, 3H)
21483 (M+H)174-177charged 8.52 (s, 1H), 8,09 (who, J=8,8 Hz, 2H), to 7.77 (d, J=9.0 Hz, 2H), 7,54-to 7.32 (m, 8H), 7,31-to 7.18 (m, 1H), PC 6.82 (s, 1H), of 1.85 (s, 6H)
22513 (M+H), 511 (M-H)131-1338,54 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9,2 Hz, 2H), 7,49 (d, J=8.6 Hz, 2H), 7,38 (d, J=8,2 Hz, 2H), 7,15 (d, J=8.7 Hz, 2H), at 6.84 (d, J=8.7 Hz, 2H), 6.73 x (s, 1H), 5,17-5,04 (m, 1H), of 3.78 (s, 3H), 2,96 (DD, J=13,8, 6.3 Hz, 1H), 2,77 (DD, J=13,8, 6,7 Hz, 1H), 1,28 (d, J=6.3 Hz, 3H)
25421 (M+H), 419 (M-H)177-1798,54 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H), 7,37 (d, J=8,3 Hz, 2H), only 6.64 (s, 1H), 1,53 (s, 9H)

28HRMS-FAB(m/z)[M+H]+calculated for C24H17F6N5O2, 521,129; found 521,1286164,5-167,08,78 (d, J=2.0 Hz, 1H), 8,63 (s, 1H), 8,14 (d, J=8,8 Hz, 2H), to $ 7.91 (m, 3H), 7,80 (d, J=8.6 Hz, 2H), 7,71-7,66 (m, 1H), 7,49 (d, J=8.7 Hz, 2H), of 6.96 (s, 1H), 5,99 (kV, J=6,7 Hz, 1H), of 1.66 (d, J=6,7 Hz, 3H)
29 HRMS-FAB(m/z)[M+H]+calculated for C26H16F6N4O2, 530,118; found 530,1175177,5-179,58,64 (s, 1H), 8,16 (d, J=8.7 Hz, 2H), of 7.90 (d, J=8.5 Hz, 2H), 7,79 (d, J=8.6 Hz, 2H), 7,75-to 7.64 (m, 4H), 7,51 (d, J=8.7 Hz, 2H), 6,93 (s, 1H), 6,56 (d, J=2.3 Hz, 1H), 2,77 (d, J=2.3 Hz, 1H)
30HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O2, 466,162; found 466,1619152-1548,69 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), of 7.90 (d, J=8.5 Hz, 2H), 7,78 (d, J=8.6 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), 7,41-7,34 (m, 4H), 7,33-7,27 (m, 1H), 6,86 (s, 1H), of 5.68 (t, J=6,9 Hz, 1H), 2,01 (doctor kV, J=22,1 that 7.4 Hz, 1H), 1,95-to 1.82 (m, 1H), of 0.95 (t, J=7.4 Hz, 3H)

31HRMS-FAB(m/z)[M+H]+calculated for C25H17F3N4O2, 462,130; found 462,1305170-1738,63 (s, 1H), 8,15 (d, J=8.7 Hz, 2H), 7,89 (d, J=8.5 Hz, 2H), 7,78 (d, J=8.6 Hz, 2H), 7,60 (DD, J=7,7, 1.8 Hz, 2H), 7,51 (d, J=8.6 Hz, 2H), 7,45-to 7.32 (m, 3H), 6.90 to (s, 1H), of 6.52 (d, J=2.2 Hz, 1H), 2,73 (d, J=2.3 Hz, 1H)
32 HRMS-FAB(m/z)[M+H]+calculated for C21H18ClF5N4O3, 504,0988; found 504,1002181-1848,55 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.0 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H), 7,38 (d, J=8,9 Hz, 2H), 6.75 in (s, 1H), with 3.89 (s, 2H), 1.61 of (s, 6H)
33588 ([M+H]+), 586 ([M-H]-)173-1758,78 (d, J=1.9 Hz, 1H), 8,55 (s, 1H), 8,14 (d, J=8,8 Hz, 2H), 7,89 (DD, J=8,1, 2.1 Hz, 1H), 7,79 (d, J=9.1 Hz, 2H), 7,74-the 7.65 (m, 1H), of 7.48 (d, J=8.7 Hz, 2H), 7,38 (d, J=9.0 Hz, 2H), 6.89 in (s, 1H), 5,99 (kV, J=6,7 Hz, 1H), of 1.66 (d, J=6,7 Hz, 3H)

34(thin film) 3230,3114, 3063, 2974, 2941, 1719, 1615, 1516, 1445, 1416, 1315, 1225, 1137, 1092, 1051, 985, 843HRMS-FAB(m/z)[M+H]+calculated for C26H21F5N4O3, 532,153; found 532,15398,89 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), a 7.85 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), 7,38 (DD, J=9,6, of 6.7 Hz, 6H), 7,33-7,26 (m, 1H), 6.89 in (s, 1H), of 5.68 (t, J=6,9 Hz, 1H), 2,08-of 1.94 (m, 1H), 1,94-of 1.81 (m, 1H), were 0.94 (t, J=7.4 Hz, 3H)
35HRMS-FAB(m/z)[M+H]+calculated for C24H18F3IN4O3, 594,0376; found 594,0411139-142,58,54 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), of 7.70 (d, J=8,4 Hz, 2H), of 7.48 (d, J=8.6 Hz, 2H), 7,38 (d, J=8,4 Hz, 2H), 7,15 (d, J=8,3 Hz, 2H), 6,79 (s, 1H), of 5.84 (q, J=6,6 Hz, 1H), 1,59 (d, J=6,7 Hz, 3H)
36HRMS-FAB(m/z)[M+H]+calculated for C27H20F3N5O3, 519,1518; found 519,1527157,5-1598,53 (s, 1H), 8,19 (d, J=8.5 Hz, 1H), 8,12 (pseudo d, J=8.7 Hz, 3H), 7,81 (d, J=8,1 Hz, 1H), 7,78 (d, J=9.0 Hz, 2H), 7,72 (DDD, J=8,4, 6,9, and 1.4 Hz, 1H), 7,58-7,47 (m, 4H), 7,37 (d, J=8,3 Hz, 2H), 7,01 (s, 1H), 6,12 (kV, J=6,7 Hz, 1H), 1,76 (d, J=6,7 Hz, 3H)

37HRMS-FAB(m/z)[M+H]+calculated for C24H21F3N5O3, 484,1591; found 484,1589152,5-1558,54 (s, 1H), 8,11 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), EUR 7.57 (t, J=7.7 Hz, 1H), 7,50 (d, J=8,8 Hz, 2H), 7,37 (DD, J=9,0, 0.7 Hz, 2H), 7.7 (d, J=7.7 Hz, 1H), 7,07 (d, J=7.7 Hz, 1H), 6,99 (s, 1H), 5,91 (kV, J=6,7 Hz, 1H), 2.57 m (s, 3H), of 1.65 (d, J=6,7 Hz, 3H)
38HRMS-FAB(m/z)[M+H]+calculated for C27H25F3N4O3, 510,1879; found 510,1889149-151charged 8.52 (s, 1H), 8,12 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), 7,40-7,35 (m, 2H), 7,33 (d, J=8,2 Hz, 2H), 7.23 percent (d, J=8.1 Hz, 2H), 6,76 (s, 1H), 5,91 (kV, J=6,6 Hz, 1H), 2,97-2,85 m, 1H), 1,62 (d, J=6.6 Hz, 3H), 1,25 (d, J=6.9 Hz, 6H)
39(thin film) 3317,1723, 1518,1263, 1224, 1071HRMS-FAB(m/z)[M+H]+calculated for C24H18BrF3N4O3, 546,0514; found 546,05138,53 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,53-7,42 (m, 4H), 7,38 (DD, J=9,0, 0.7 Hz, 2H), 7,28 (d, J=8,4 Hz, 2H), 6,76 (s, 1H), by 5.87 (q, J=6,6 Hz, 1H), 1,60 (d, J=6.6 Hz, 3H)

40HRMS-FAB(m/z)[M+H]+calculated for C28H27F3N4O3, 524,2035; found 524,2058189-190,5 8,53 (s, 1H), 8,12 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), 7,43-7,31 (m, 6H), 6,79 (s, 1H), of 5.92 (q, J=6,6 Hz, 1H), 1,62 (d, J=6.6 Hz, 3H), of 1.32 (s, 9H)
41HRMS-FAB(m/z)[M+H]+calculated for C24H17F6N5O3, 537,124; found 537,1235154-1568,78 (d, J=1.8 Hz, 1H), 8,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,89 (DD, J=8,1, 2.0 Hz, 1H), 7,78 (d, J=9.0 Hz, 2H), 7,69 (d, J=8,1 Hz, 1H), of 7.48 (d, J=8.5 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H), 6,94 (s, 1H), of 5.99 (q, J=6,6 Hz, 1H), of 1.66 (d, J=6,7 Hz, 3H)
42HRMS-FAB(m/z)[M+H]+calculated for C25H18F6N4O3, 536,128; found 536,1284128-131(400 MHz, DMSO-d6) 10,11 (s, 1H), 9,36 (s, 1H), with 8.05 (d, J=9.1 Hz, 2H), 8,01 (d, J=8.7 Hz, 2H), to 7.77 (d, J=8,2 Hz, 2H), 7,65 (d, J=8,2 Hz, 2H), 7,60 (d, J=8.6 Hz, 4H), 5,90 (kV, J=6,5 Hz, 1H), 1,57 (d, J=6.6 Hz, 3H)

43(thin film) 3318, 1734, 1519, 1327, 1265, 1220HRMS-FAB(m/z)[M+H]+calculated for C30H20F6N4O 3, 598,144; found 598,14458,54 (s, 1H), 8,14 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,63 (d, J=8,2 Hz, 2H), 7,55-7,47 (m, 4H), 7,42-7,30 (m, 7H), to 6.95 (s, 1H), 6,94 (s, 1H)
44493 ([M+H]+), 491 ([M-H]-)132-134,58,53 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,53-the 7.43 (m, 4H), 7,41-to 7.32 (m, 4H), 6,78 (s, 1H), 5,90 (kV, J=6,6 Hz, 1H), of 3.07 (s, 1H), 1,60 (d, J=6.6 Hz, 3H)
45494 ([M+H]+), 492 ([M-H]-)186,5-187,58,54 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), to 7.67 (d, J=8,4 Hz, 2H), 7,55-the 7.43 (m, 4H), 7,38 (DD, J=8,9, 0.6 Hz, 2H), for 6.81 (s, 1H), of 5.92 (q, J=6,6 Hz, 1H), 1,61 (d, J=6,7 Hz, 3H)

46470 ([M+H]+), 468 ([M-H]-)143-1458,61 (DDD, J=4,8, of 1.6, 0.8 Hz, 1H), 8,54 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,69 (TD, J=7,7, 1.8 Hz, 1H), 7,49 (d, J=8,8 Hz, 2H), 7,41-to 7.32 (m, 3H), 7,22 (DDD, J=7,5, a 4.9, 1.1 Hz, 1H), 7,08 (s, 1H), 5,95 (kV, J=6,6 Hz, 1H), of 1.66 (d, J=6,7 Hz, 3H)
47484 ([M+H]+), 482 ([M-H]-)55-758,93 (d, J=1.6 Hz, 1H), 8,55 (s, 1H), 8,14 (d, J=8,8 Hz, 2H), 8,07 (DD, J=8,2, 2.0 Hz, 1H), 7,79 (d, J=9.0 Hz, 2H), 7,50 (pseudo t, J=8,9 Hz, 3H), 7,42-7,34 (m, 2H), 7,06 (s, 1H), 5,98 (kV, J=6,6 Hz, 1H), 2,80 (s, 3H), 1,67 (d, J=6,7 Hz, 3H)
48(thin film) 3243, 1731, 1607, 1548, 1518, 1445, 1416, 1313, 1228470 ([M+H]+), 468 ([M-H]-)(400 MHz, CD3OD) 9,03 (s, 1H), 8,51 (DD, J=4,6, and 1.6 Hz, 2H), 8,02 (d, J=8,9 Hz, 2H), 7,94 (d, J=9.1 Hz, 2H), 7,54 (d, J=8,8 Hz, 2H), 7,45 (DDD, J=9,6, 6,8, 1.0 Hz, 4H), 5,86 (kV, J=6,6 Hz, 1H), 1,58 (d, J=6,7 Hz, 3H)

49HRMS-FAB(m/z)[M+H]+calculated for C26H20F6N4O3, 550,144; found 550,146168,5-1718,51 (s, 1H), 8,10 (d, J=8,8 Hz, 2H), 7,76 (d, J=9.0 Hz, 2H), 7,60 (d, J=8,3 Hz, 2H), 7,52 (d, J=8,3 Hz, 2H), 7,44 (d, J=8,8 Hz, 2H), 7,39-7,31 (m, 2H), 6.89 in (s, 1H), of 1.84 (s, 6H)
50 HRMS-FAB(m/z)[M+H]+calculated for C24H16F6N4O3, 522,1127; found 522,1139KZT 166.5-1688,53 (s, 1H), 8,15 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), to 7.64 (d, J=8.1 Hz, 2H), EUR 7.57 was 7.45 (m, 4H), 7,37 (DD, J=9,0, 0.8 Hz, 2H), 6,92 (s, 1H), 5,27 (s, 2H)
51HRMS-FAB(m/z)[M+H]+calculated for C24H17F6N5O4, 553,1185; found 553,1191199-202,5(300 MHz, DMSO-d6) 10,16 (s, 1H), 9,36 (s, 1H), 8,59 (s, 1H), 8,10-to 7.95 (m, 5H), 7.68 per is 7.50 (m, 5H), 5,86 (kV, J=6,5 Hz, 1H), 1,58 (d, J=6.6 Hz, 3H)
52HRMS-FAB(m/z)[M+H]+calculated for C24H15ClF3N5O3, 513,0816; found 513,0832156,5-158(300 MHz, acetone-d6) 9,18 (s, 1H), 9,13 (s, 1H), 8,66 (d, J=2.4 Hz, 1H), 8,16 (d, J=8,8 Hz, 2H), 8,13-of 8.06 (m, 3H), 7,71 (d, J=8.7 Hz, 2H), 7,63-7,52 (m, 3H), 6,63 (d, J=2.3 Hz, 1H), 3.46 in (d, J=2.3 Hz, 1H)

53HRMS-FAB(m/z)[M+H]+calculated for C25H15ClF6N5O3, 547,1079; found 547,1098177-179(300 MHz, acetone-d6) 9,24 (s, 1H), 9,13 (s, 1H), 9,02 (d, J=1.9 Hz, 1H), with 8.33 (DD, J=8,1, 2.1 Hz, 1H), 8,16 (d, J=8,8 Hz, 2H), 8,10 (d, J=9.1 Hz, 2H), of 7.97 (d, J=8,2 Hz, 1H), 7,72 (d, J=8,8 Hz, 2H), 7,63-7,52 (m, 2H), 6,74 (d, J=2.3 Hz, 1H), 3,51 (d, J=2.3 Hz, 1H)
54(thin film) 3248, 3111, 3062, 1728, 1608, 1518, 1445, 1417, 1262, 1223, 1053HRMS-FAB(m/z)[M+H]+calculated for C21H15ClF3N5O3S, 509,054; found 509,05318,54 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,55 (s, 1H), 7,49 (d, J=8.6 Hz, 2H), 7,38 (d, J=8,8 Hz, 2H), 6,83 (s, 1H), 6,09 (kV, J=6,6 Hz, 1H), 1,71 (d, J=6.6 Hz, 3H)
55(thin film) 3307, 3119, 2986, 2950, 1725, 1611, 1517, 1495, 1445, 1416, 1257, 1215HRMS-FAB(m/z)[M+H]+calculated for C24H20F3N5O4, 499,147; found 499,14638,53 (s, 1H), they were 8.22 (d, J=2.4 Hz, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,63 (DD, J=8,6, 2.5 Hz, 1H), of 7.48 (d, J=8.7 Hz, 2H), 7,42-to 7.32 (m, 2H), for 6.81 (s, 1H), 6.75 in (d, J=8.6 Hz, 1H), of 5.89 (kV, J=6,6 Hz, 1H), 393 (, 3H), of 1.61 (d, J=6.6 Hz, 3H)

56(thin film) 3259, 3117, 3062, 2986, 1729, 1597, 1518, 1445, 1417, 1263, 1225HRMS-FAB(m/z)[M+H]+calculated for C23H17ClF3N5O3, 503,097; found 503,09708,54 (s, 1H), 8,45 (d, J=2.5 Hz, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,68 (DD, J=8,3, 2.5 Hz, 1H), of 7.48 (d, J=8.5 Hz, 2H), 7,37 (DD, J=8,9, 0.6 Hz, 2H), 7,33 (d, J=8,3 Hz, 1H), 6,97 (s, 1H), 5,91 (kV, J=6,6 Hz, 1H), 1,62 (d, J=6,7 Hz, 3H)
57539 ([M+H]+), 537 ([M-H]-)185-187to 8.94 (s, 2H), 8,55 (s, 1H), 8,15 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), of 7.48 (d, J=8.6 Hz, 2H), was 7.36 (d, J=0.7 Hz, 2H), 6,91 (s, 1H), 6,01 (kV, J=6,7 Hz, 1H), 1,71 (d, J=6.8 Hz, 3H)
58(thin film) 3295, 3120, 3066, 3036, 2934, 2894, 1728, 1597, 1518, 1493, 1445, 1263, 1223HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O4, 498,152; found 498,15118,54 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H),7,49 (l, J=8,8 Hz, 2H), 7,44-7,31 (m, 7H), 6,97 (s, 1H), of 5.99 (DD, J=8,0, 3.6 Hz, 1H), 3,80 (DD, J=10,9, 8.0 Hz, 1H), 3,63 (DD, J=10,9, and 3.7 Hz, 1H), 3.43 points (s, 3H)

59HRMS-FAB(m/z)[M+H]+calculated for C24H19F3N4O3, 468,140; found 468,141136-1388,53 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.6 Hz, 2H), 7,45-7,34 (m, 6H), 7,34-7,28 (m, 1H), PC 6.82 (s, 1H), of 5.92 (q, J=6,6 Hz, 1H), 1,62 (d, J=6.6 Hz, 3H)
60469 ([M+H]+)122,5-125,08,54 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.6 Hz, 2H), 7,46-7,34 (m, 6H), 7,34-7,28 (m, 1H), 6,78 (s, 1H), of 5.92 (q, J=6,6 Hz, 1H), and 1.63 (d, J=6.6 Hz, 3H)
61469 ([M+H]+)123,5-125,08,53 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), 7,44-7,34 (m, 6H), 7,34-7,28 (m, 1H), for 6.81 (s, 1H), of 5.92 (q, J=6,6 Hz, 1H), 1,62 (d, J=6.6 Hz, 3H)
62 (thin film) 3320, 3120, 2973, 2938, 1722, 1596, 1518, 1490, 1445, 1416, 1314, 1263, 1222, 1051, 732562 ([M+H]+)8,53 (s, 1H), 8,12 (d, J=8,8 Hz, 2H), 7,78 (d, J=9,2 Hz, 2H), 7,58-7,40 (m, 4H), 7,37 (DD, J=9,0, 0.8 Hz, 2H), 7,28-7,14 (m, 2H), 6,85 (s, 1H), 5,62 (t, J=6,9 Hz, 1H), 2,11-of 1.73 (m, 2H), of 0.93 (t, J=7,4 Hz, 3H)

63(thin film) 3318, 3121, 3064, 2973, 2938, 1720, 1596,1518, 1491, 1445, 1416, 1313, 1263, 1222, 1051, 909, 732HRMS-FAB(m/z)[M+H]+calculated for C25H20BrF3N4O3, 560,067; found 560,06728,54 (s, 1H), 8,12 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,54-7,47 (m, 3H), 7,43 (DDD, J=7,7, to 1.9, and 1.4 Hz, 1H), 7,37 (DD, J=9,0, 0.8 Hz, 2H), 7,29 (dt, J=7,9, 1.5 Hz, 1H), 7,22 (t, J=7.7 Hz, 1H), 6.90 to (C, 1H), 5,62 (t, J=6,8 Hz, 1H), 2,08-of 1.74 (m, 2H), were 0.94 (t, J=7.4 Hz, 3H)
64HRMS-FAB(m/z)[M+H]+calculated for C25H18F6N4O4, 552,123; found 552,1230110-1138,54 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), 7,43 (d, J=8.6 Hz, 2H), 7,38 (DD, J=9,0, 0.8 Hz, 2H), 7,22 (DD, J=8,7, 0.8 Hz, 2H), for 6.81 (s, 1H), 5,91 (kV, J=6,6 Hz, 1H), to 1.61 (d, J6,6 Hz, 3H)
65(thin film) 3229, 3181, 3108, 3048, 1742, 1600, 1541, 1519, 1441, 1417, 1310, 1248, 1222, 1083, 985, 843HRMS-FAB(m/z)[M+H]+calculated for C25H20ClF3N4O3, 516,118; found 516,11748,54 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,50 (d, J=8,8 Hz, 2H), 7,40-7,34 (m, 3H), 7,31-7,19 (m, 3H), 6,86 (s, 1H), 5,64 (t, J=6,9 Hz, 1H), 2,08-of 1.74 (m, 2H), were 0.94 (t, J=7.4 Hz, 3H)

66(thin film) 3250, 3117, 3061, 2126, 1735, 1610, 1549, 1519, 1492, 1445, 1417, 1328, 1263, 1220, 1068, 1050, 848HRMS-FAB(m/z)[M+H]+calculated for C26H16F6N4O3, 546,113; found 546,11258,55 (s, 1H), 8,15 (d, J=8,8 Hz, 2H), 7,83 to 7.75 (m, 2H), 7,75-to 7.64 (m, 4H), 7,51 (d, J=8.7 Hz, 2H), 7,43-7,34 (m, 2H), 6.90 to (s, 1H), 6,56 (d, J=2.2 Hz, 1H), was 2.76 (d, J=2.4 Hz, 1H)
67HRMS-FAB(m/z)[M+H]+calculated for C26H20F6N4O3, 550,144; found 550,1440161,5-163,0 8,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,63 (d, J=8,2 Hz, 2H), 7,49 (d, J=8.5 Hz, 2H), of 7.48 (d, J=8.5 Hz, 2H), 7,43-7,27 (m, 2H), 6,85 (s, 1H), 5,71 (t, J=6,8 Hz, 1H), 2,11-1,73 (m, 2H), of 0.96 (t, J=7.4 Hz, 3H)
68HRMS-FAB(m/z)[M+H]+calculated for C25H18F6N4O3, 536,128; found 536,1282118-119,58,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), to 7.67 (s, 1H), 7,63-of 7.55 (m, 2H), 7,54-7,46 (m, 3H), 7,38 (DD, J=9,0, 0.7 Hz, 2H), 6,85 (s, 1H), 5,96 (kV, J=6,6 Hz, 1H), and 1.63 (d, J=6.6 Hz, 3H)

69HRMS-FAB(m/z)[M+H]+calculated for C25H18F6N4O3, 536,128; found 536,1282which is 171,5-173.5 metric8,53 (s, 1H), 8,11 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), to 7.67 (pseudo t, J=7,0 Hz, 2H), 7,58 (DD, J=11,3, 3,9 Hz, 1H), 7,49 (d, J=8.7 Hz, 2H), 7,44-to 7.32 (m, 3H), 6,85 (s, 1H), 6,27 (kV, J=6,5 Hz, 1H), 1,61 (d, J=6.5 Hz, 3H)
70HRMS-FAB(m/z)[M+H]+calculated for C25H19F3N4O3, 480,141; found 480,1411 118-1218,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), 7,46-7,30 (m, 7H), 6.89 in (s, 1H), 6,29 (d, J=5,9 Hz, 1H), 6,09 (DDD, J=17,0, 10,4, 5,9 Hz, 1H), 5,38 (dt, J=17,2, 1.3 Hz, 1H), 5,31 (dt, J=10,5, 1.2 Hz, 1H)
71HRMS-FAB(m/z)[M+H]+calculated for C27H25F3N4O3, 510,188; found 510,1884146,5-148,58,53 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), 7,41-7,33 (m, 6H), 7,32-7,27 (m, 1H), 6,83 (s, 1H), 5,74 (DD, J=7,5, 6.5 Hz, 1H), 2,09 is 1.91 (m, 1H), 1.91 a-1,71 (m, 1H), 1,59-1,02 (m, 4H), to 0.89 (t, J=7.0 Hz, 3H)

72(thin film) 3317, 3123, 3066, 3036, 2246, 1731, 1598, 1518, 1492, 1445, 1416, 1263, 1217, 1039, 986, 909, 850, 732HRMS-FAB(m/z)[M+H]+calculated for C26H19F3N4O3, 492,141; found 492,14138,53 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), to 7.77 (d, J=9.0 Hz, 2H), 7,58 (DD, J=7,9, and 1.6 Hz, 2H), 7,50 (d, J=8.6 Hz, 2H), 7,44-to 7.32 (m, 5H), 6,91 (s, 1H), of 6.49 (kV, J=2.1 Hz, 1H), 1,93 (d, J=2.2 Hz, 3H)
73 HRMS-FAB(m/z)[M+H]+calculated for C24H17Cl2F3N4O3, 536,063; found 536,0634196-1988,69 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.7 Hz, 2H), 7,37 (d, J=8.6 Hz, 2H), 7,30 (d, J=8.0 Hz, 2H), 7,14 (DD, J=8,4, 7.7 Hz, 1H), 6.90 to (s, 1H), 6,56 (kV, J=6,9 Hz, 1H), of 1.73 (d, J=6.9 Hz, 3H)
74(thin film) 3251, 3111, 3064, 2962, 2874, 1724, 1607, 1518, 1493, 1445, 1416, 1313, 1262, 1225, 1179, 1107, 1058HRMS-FAB(m/z)[M+H]+calculated for C26H23F3N4O3, 496,172; found 496,17278,98 (s, 1H), 8,08 (d, J=8.1 Hz, 2H), 7,86-7,74 (m, 2H), 7,44 (d, J=7.8 Hz, 2H), was 7.36-7,26 (m, 6H), 7,26-7,20 (m, 1H), 6,80 (s, 1H), 5,69 (DD, J=7,4, 6.5 Hz, 1H), 1,96 of-1.83 (m, 1H), 1,80-of 1.66 (m, 1H), 1,46-1,19 (m, 2H), from 0.88 (t, J=7.4 Hz, 3H)

75HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O5S, 546,118; found 546,1187131-1358,56 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,95 (d, J=8,4 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,60 (d, J=8,4 Hz, 2H), 7,49 (d, J=8.6 Hz, 2H), 7,38 (d, J=8,4 Hz, 2H), 6.87 in (s, 1H), 5,95 (kV, J=6,6 Hz, 1H), 3,05 (s, 3H), and 1.63 (d, J=6,7 Hz,3H)
76HRMS-FAB(m/z)[M+H]+calculated for C22H17F3N4O3S, 474,097; found 474,0976158-160(400 MHz, DMSO-d6) 10,00 (s, 1H), 9,37 (s, 1H), of 8.06 (d, J=9.0 Hz, 2H), 8,01 (d, J=8.7 Hz, 2H), to 7.67-7,56 (m, 4H), 7,53 (DD, J=5,1, 1.2 Hz, 1H), 7,19 (d, J=3,4 Hz, 1H), 7,03 (DD, J=5, 1,3,5 Hz, 1H), 6,11 (kV, J=6,5 Hz, 1H), of 1.66 (d, J=6.6 Hz, 3H)
77HRMS-FAB(m/z)[M+H]+calculated for C22H17F3N4O3S, 474,097; found 474,0979135-137(400 MHz, DMSO-d6) 9,96 (s, 1H), 9,36 (s, 1H), with 8.05 (d, J=9.0 Hz, 2H), 8,01 (d, J=8.7 Hz, 2H), 7.62mm (d, J=8.6 Hz, 2H), 7,60 (d, J=8.6 Hz, 2H), EUR 7.57-7,51 (m, 2H), 7,20 (DD, J=4,8, 1.5 Hz, 1H), 5,93 (kV, J=6,5 Hz, 1H), 1,59 (d, J=6.6 Hz, 3H)

78(thin film) 3251, 3064, 2960, 1724, 1608, 1518, 1493, 1445, 1416, 1313, 1262, 1224, 1179, 1056, 849HRMS-FAB(m/z)[M+H]+calculated for C27H25F3N4O3, 510,1883; found 510,187 8,93 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), to 7.84 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.7 Hz, 2H), 7,44-to 7.32 (m, 6H), 7,30 (DDD, J=6,7, and 3.8, 1.7 Hz, 1H), 6,86 (s, 1H), of 5.83 (DD, J=8,6, a 5.3 Hz, 1H), 2,03 and 1.80 (m, 1H), 1,75-of 1.52 (m, 2H), and 0.98 (d, J=6.3 Hz, 3H), of 0.97 (d, J=6.2 Hz, 3H)
79HRMS-FAB(m/z)[M+H]+calculated for C25H20F4N4O3, 500,147; found 500,1475123-1268,88 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,83 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.6 Hz, 2H), 7,43-7,30 (m, 4H),? 7.04 baby mortality (t, J=8.7 Hz, 2H), 6,91 (s, 1H), 5,64 (t, J=7,0 Hz, 1H), 2,07 is 1.91 (m, 1H), 1,91 is 1.75 (m, 1H)that is 0.92 (t, J=7.4 Hz, 3H)
80HRMS-FAB(m/z)[M+H]+calculated for C22H14F6N4O4, 512,092; found 512,091997-998,71 (s, 1H), 8,17 (d, J=8.7 Hz, 2H), 7,81 (d, J=9.0 Hz, 2H), 7,66 (s, 1H), 7,51 (d, J=8,4 Hz, 2H), 7,46 (t, J=1.7 Hz, 1H), 7,39 (d, J=8.5 Hz, 2H), 7,05 (s, 1H), 6,55 (s, 1H), 6.22 per (kV, J=6,8 Hz, 1H)

81HRMS-FAB(m/z)[M+H]+calculated for C24H18F3N4O3Cl, 502,102; neid is but 502,1020 144-1478,58 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.6 Hz, 2H), 7,38 (d, J=8,3 Hz, 2H), 7,34 (pseudo s, 4H), to 6.80 (s, 1H), by 5.87 (q, J=6,6 Hz, 1H), 1,59 (d, J=6.6 Hz, 3H)
82HRMS-FAB(m/z)[M+H]+calculated for C25H17F3N4O3, 478,125; found 478,1256142-144(400 MHz, DMSO-d6) 10,19 (s, 1H), 9,37 (s, 1H), 8,04 (DD, J=10,4, a 8.9 Hz, 4H), 7.68 per-7,56 (m, 6H), 7,51-7,29 (m, 3H), 6,47 (d, J=2.2 Hz, 1H), 3,88 (d, J=2.2 Hz, 1H)
83HRMS-FAB(m/z)[M+H]+calculated for C29H21F3N4O3, 530,157; found 530,1564158-1608,99 (s, 1H), 8,18 (d, J=8.7 Hz, 2H), 7,87 (d, J=9.0 Hz, 2H), 7,56 (d, J=8.7 Hz, 2H), 7,47-7,30 (m, 12H), to 7.09 (s, 1H), 6,94 (s, 1H)
84HRMS-FAB(m/z)[M+H]+calculated for C24H18F4N4O3, 486,131; found 486,1318142-1448,56 (s, 1H), 8,12 (d, J=8,4 Hz, 2H), 7,78 (d, J=8.6 Hz, 2H), 7,49 (who, J=8,2 Hz, 2H), 7,38 (DD, J=8,6, a 5.4 Hz, 4H), 7,05 (t, J=8.7 Hz, 2H), 6,85 (s, 1H), of 5.89 (q, J=6,6 Hz, 1H), 1,60 (d, J=6.6 Hz, 3H)

85HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O3, 482,156; found 482,1568127-1318,53 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,76 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.6 Hz, 2H), 7,42-to 7.15 (m, 7H), 6,97 (s, 1H), of 5.68 (t, J=6,9 Hz, 1H), 2,07 is 1.75 (m, 2H), were 0.94 (t, J=7.4 Hz, 3H)
86HRMS-FAB(m/z)[M+H]+calculated for C23H20F3N5O4, 487,146; found 487,14688,55 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,49 (d, J=8,4 Hz, 2H), 7,38 (d, J=8,3 Hz, 2H), 6,91 (s, 1H), of 5.82 (q, J=6,8 Hz, 1H), 2,46 (s, 3H), of 2.36 (s, 3H), 1,60 (d, J=6.9 Hz, 3H)
87HRMS-FAB(m/z)[M+H]+calculated for C19H17F3N4O3, 406,125; found 406,1252193-1958,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,50 (d, J=5 Hz, 2H), 7,37 (d, J=8.5 Hz, 2H), of 6.71 (s, 1H), 5,23-4,88 (m, 1H), 1,31 (d, J=6.3 Hz, 6H)
88HRMS-FAB(m/z)[M+H]+calculated for C26H21F3N4O3, 494,156; found 494,15678,54 (s, 1H), 8,12 (d, J=8,8 Hz, 2H), 7,79 (d, J=9.1 Hz, 2H), 7,50 (d, J=8,8 Hz, 2H), 7,46-7,28 (m, 7H), PC 6.82 (s, 1H), total of 5.21 (d, J=8,9 Hz, 1H), 1,45-of 1.29 (m, 1H), 0.76 to be 0.56 (m, 3H), 0,51-0,38 (m, 1H)

89HRMS-FAB(m/z)[M+H]+calculated for C26H23F3N4O3, 496,172; found 496,1726181-1838,53 (s, 1H), 8,11 (d, J=8,4 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.5 Hz, 2H), 7,37 (d, J=8.5 Hz, 2H), 7,07 (DD, J=8,5, 6.3 Hz, 1H), 7,01 (d, J=7,4 Hz, 2H), 6,79 (s, 1H), 6,34 (kV, J=6,9 Hz, 1H), of 2.50 (s, 6H), of 1.65 (d, J=7,0 Hz, 3H)
90HRMS-FAB(m/z)[M+H]+calculated for C24H16F6N4O3, 522,112; found 522,11288,55 (s, 1H), 8,15 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,58-7,46 (m,4H), of 7.48-7,34 (m, 5H), 7,1 1 (s, 1H), 6,17 (kV, J=6,9 Hz, 1H)
91HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O3, 482,156; found 482,156160-1628,53 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), to 7.77 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.6 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H), 7,30 (d, J=8.1 Hz, 2H), 7,18 (d, J=7.9 Hz, 2H), at 6.84 (s, 1H), of 5.89 (q, J=6,6 Hz, 1H), 2,34 (s, 3H), of 1.61 (d, J=6.6 Hz, 3H)

92HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O3, 482,156; found 482,15794-978,53 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.6 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H), 7,30-7,17 (m, 3H), 7,12 (d, J=7.5 Hz, 1H), 6,86 (s, 1H), 5,88 (kV, J=6,6 Hz, 1H), is 2.37 (s, 3H), to 1.61 (d, J=6.6 Hz, 3H)
93HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O3, 482,156; found 482,157147-1498,53 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), to 7.77 (d, J=9.0 Hz, 2H), 7,49 d, J=8.6 Hz, 2H), 7,45-7,39 (m, 1H), 7,37 (d, J=8.7 Hz, 2H), 7,27-7,11 (m, 3H), 6.90 to (s, 1H), 6,13 (kV, J=6,5 Hz, 1H), 2,43 (s, 3H), of 1.59 (d, J=6.6 Hz, 3H)

94525 ([M+H]+)>150(3:2 mixture of diastereomers) charged 8.52 (s, 1H), 8,11 (d, J=8.6 Hz, 2H), to 7.77 (d, J=9.0 Hz, 2H), to 7.59-the 7.43 (m, 2H), 7,37 (d, J=8,4 Hz, 2H), 6,98-6,89 (m, 2H), 6,82-6,63 (m, 2H), to 6.39 (d, J=2.2 Hz, 0.6 a (H), and 6.25 (d, J=3.0 Hz, 0,4 H), 3,76-3,62 (m, 0,6 H)to 3.09 (DD, J=16,4, 5,9 Hz, 0,4 H)to 2.67 (d, J=9.0 Hz, H 1,2), 2,33-of 2.20 (m, 0,8 H), and 2.27 (s, 3H), 1.14 in (d, J=6,8 Hz, 1,5 H)a 1.08 (d, J=7,1 Hz, 1,5 H)
95HRMS-FAB(m/z)[M+H]+calculated for C25H19F3N4O4, 496,135; found 496,136171-1738,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9,2 Hz, 2H), 7,50 (d, J=8.5 Hz, 2H), 7,38 (DD, J=9,1, 0.8 Hz, 2H), 7,13 (DD, J=15,8, and 7.8 Hz, 2H), 6,94 (DDD, J=a 9.7 and 7.6, 1.7 Hz, 2H), 6,76 (s, 1H), 6,62 (t, J=the 2.5 Hz, 1H), 3,03 (DDD, J=17.4 years, 12,3, 5,9 Hz, 1H), 2,77 (DDD, J=17,0, 6,2, 3.1 Hz, 1H), 2,33-to 1.98 (m, 2H)

96HRMS-FAB(m/z)[M+H]+ 23H21F3N4O3, 458,156; found 458,157158-1598,53 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.6 Hz, 2H), was 7.36 (d, J=8,4 Hz, 2H), 6,77 (s, 1H), 2,23 (kV, J=7.5 Hz, 2H), 1,73 (s, 6H), of 1.13 (t, J=7.5 Hz, 3H)
97(thin film) 3317, 3122, 2981, 2933, 2839, 1724, 1615, 1518, 1492, 1445, 1416, 1249, 1225, 1179, 1111, 1064, 986, 847HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O4, 498,151; found 498,1518,53 (s, 1H), 8,11 (d, J=8.7 Hz, 2H), 7,78 (d, J=8,9 Hz, 2H), of 7.48 (d, J=8.6 Hz, 2H), 7,37 (d, J=8,9 Hz, 2H), 7,35 (d, J=8,8 Hz, 2H), make 6.90 (d, J=8.7 Hz, 2H), 6,79 (s, 1H), 5,88 (kV, J=6,6 Hz, 1H), 3,80 (s, 3H), of 1.61 (d, J=6.6 Hz, 3H)
98HRMS-FAB(m/z)[M+H]+calculated for C18H15F3N4O3, 392,109; found 392,109182-1848,55 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.5 Hz, 2H), 7,37 (d, J=8.5 Hz, 2H), for 6.81 (s, 1H), 4,25 (kV, J=7,1 Hz, 2H), 1,32 (t, J=7,1 Hz, 3H)

99 HRMS-FAB(m/z)[M+H]+calculated for C24H24F3N5O3, 487,183; found 487,183130 - 133(300 MHz, CDCl3CD3OD) at 8.60 (s, 1H), of 7.97 (d, J=8 Hz, 2H), of 7.75 (d, J=8 Hz, 2H), 7,44 (d, J=8 Hz, 2H), 7,30 (d, J=8 Hz, 2H), 3,83 (width, 1H), 3,21 (s, 2H), 2,22 (s, 6H), of 1.65 (s, 6H)
100HRMS-FAB(m/z)[M+H]+calculated for C27H25F3N4O4, 526,182; found 526,183173-1768,53 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), to 7.77 (d, J=9.0 Hz, 2H), 7,50 (d, J=8,2 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H), 7,14 (d, J=8.6 Hz, 2H), 6,83 (d, J=8.7 Hz, 2H), 6,77 (s, 1H), of 3.78 (s, 3H), of 3.12 (s, 2H), of 1.50 (s, 6H)
101HRMS-FAB(m/z)[M+H]+calculated for C24H27F3N4O3, 476,203; found 476,204111-1158,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), 7,52 (d, J=8.6 Hz, 2H), 7,37 (d, J=8,3 Hz, 2H), 6,79 (s, 1H), 4,86 was 4.76 (m, 1H), 1,71 of 1.50 (m, 4H), 1,47 is 1.16 (m, 6H), were 0.94 (t, J=7.4 Hz, 3H), to 0.88 (t, J=6,7 Hz, 3H)

102 HRMS-FAB(m/z)[M+H]+calculated for C24H27F3N4O3, 476,203; found 476,204123-1248,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.5 Hz, 2H), 7,37 (d, J=8.5 Hz, 2H), 6,76 (s, 1H), 5,07-to 4.81 (m, 1H), 1,96 is 1.58 (m, 1H), 1,58 to 1.47 (m, 1H), 1,47-1,17 (m, 8H), 1,29 (d, J=6.2 Hz, 3H), from 0.88 (t, J=6,7 Hz, 3H)
103HRMS-FAB(m/z)[M+H]+calculated for C22H23F3N4O3, 448,172; found 448,172165-1668,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,52 (d, J=8,4 Hz, 2H), 7,37 (d, J=8.6 Hz, 2H), 6,77 (s, 1H), 4,71 (kV, J=6,4 Hz, 1H), 1,22 (d, J=6.4 Hz, 3H), of 0.95 (s, 9H)
104HRMS-FAB(m/z)[M+H]+calculated for C17H13F3N4O3, 378,093; found 378,094171-1738,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,50 (d, J=8.5 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H), 6,85 (s, 1H), 3,80 (s, 3H)

105 HRMS-FAB(m/z)[M+H]+calculated for C23H17F3N4O3, 454,125; found 454,125155-1578,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.5 Hz, 2H), 7,46-to 7.32 (m, 7H), 6.89 in (s, 1H), 5,22 (s, 2H)
106HRMS-FAB(m/z)[M+H]+calculated for C22H19F3N4O3, 480,140; found 480,141196 - 197charged 8.52 (s, 1H), 8,11 (d, J=8.6 Hz, 2H), to 7.77 (d, J=8,9 Hz, 2H), 7,47 (d, J=8,2 Hz, 2H), 7,37 (d, J=8.7 Hz, 2H), 7,30-7,24 (m, 2H), 7.24 to 7,16 (m, 2H), 6,78 (s, 1H), 5,63-to 5.58 (m, 1H), 3,35 (DD, J=17,0, 6,1 Hz, 2H), 3,11 (DD, J=17,0, and 2.3 Hz, 2H)
107HRMS-FAB(m/z)[M+H]+calculated for C25H21F3N4O3, 482,156; found 482,1567143-1458,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), of 7.48 (d, J=8,4 Hz, 2H), 7,37 (d, J=8,4 Hz, 2H), 7,34-7,27 (m, 2H), 7,27-7,19 (m, 3H), 6,76 (s, 1H), 5,16 (d, J=6.3 Hz, 1H), to 3.02 (DD, J=13,7, 6,4 Hz, 1H), and 2.83 (DD, J=13,7, 6,7 Hz, 1H), 1,30 (d, J=6.3 Hz, 3H)

108 HRMS-FAB(m/z)[M+H]+calculated for C26H21F3N4O3, 494,156; found 494,157197-2018,54 (s, 1H), 8,12 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,47 (d, J=8,2 Hz, 2H), 7,38 (d, J=8,3 Hz, 2H), 7.23 percent-7,11 (m, 4H), of 6.68 (s, 1H), 3,51 (d, J=16.5 Hz, 2H), 3,20 (d, J=16.5 Hz, 2H), 1,78 (s, 3H)
109HRMS-FAB(m/z)[M+H]+calculated for C25H19F3N4O3, 480,140; found 480,1415187-1908,54 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=7,0 Hz, 3H), 7,38 (d, J=8,4 Hz, 2H), 7,35-7,21 (m, 3H), 6,77 (s, 1H), of 6.26 (DD, J=6,9, 3.5 Hz, 1H), 3,19-3,10 (m, 1H), 2,92 (DDD, J=16,1, 8,6, 4.6 Hz, 1H), 2,62-2,49 (m, 1H), 2,21 (dddd, J=14,0, 8,3, 4,5, and 3.7 Hz, 1H)
110HRMS-FAB(m/z)[M+H]+calculated for C23H18F3N5O3, 469,136; found 469,1366147-150to 8.70 (s, 1H), 8,58 (d, J=4,1 Hz, 1H), 8,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,73 (dt, J=7,9, 1.7 Hz, 1H), 7,50 (d, J=8.6 Hz, 2H), 7,37 (d, J=8.5 Hz, 2H), 7,32 (DD, J=7,8, and 4.9 Hz, 1H), 7,11 (s, 1H), 5,95 (kV, J=6,6 Hz, 1H), 1,65 (d, J=6,7 Hz, 3H)

111HRMS-FAB(m/z)[M+H]+calculated for C23H15F3N4O3Cl2, 522,047; found 522,0480171-1738,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,51 (d, J=8,4 Hz, 2H), 7,43-to 7.32 (m, 4H), from 7.24 (DD, J=8,7, 7,3 Hz, 1H), 6,92 (s, 1H), 5,51 (s, 2H)
112HRMS-FAB(m/z)[M+H]+calculated for C24H16F3N5O3, 479,120; found 479,1206134-1368,56 (s, 1H), 8,16 (d, J=8.6 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,58 (DD, J=6,8, 2,9 Hz, 2H), 7,55-the 7.43 (m, 5H), 7,38 (d, J=8,4 Hz, 2H), was 7.08 (s, 1H), 6,53 (s, 1H)
113HRMS-FAB(m/z)[M+H]+calculated for C21H21F3N4O3, 434,156; found 434,1568161-1629,05 (s, 1H), 8,17 (d, J=8.7 Hz, 2H), 7,87 (d, J=8,9 Hz, 2H), 7,54 (d, J=8.5 Hz, 2H), 7,39 (d, J=8.5 Hz, 2H), 6,80 (s, 1H), 4.80 to 4,71 (m, 1H), 1,72-of 1.53 (m, 4H), of 0.95 (t, J=7.4 Hz, 6H)
114 HRMS-FAB(m/z)[M+H]+calculated for C24H14F3N4O3, 558,094; found 558,0937185-1888,54 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), of 7.48 (d, J=8.7 Hz, 2H), 7,38 (DD, J=9,0, 0.8 Hz, 2H), at 6.84 (s, 1H), 6,18 (kV, J=6,7 Hz, 1H), 1,72 (d, J=6.9 Hz, 3H)

115HRMS-FAB(m/z)[M+H]+calculated for C26H17F9N4O3, 604,116; found 604,1154212,5-214,5and 10.20 (s, 1H), 9,35 (s, 1H), to 8.20 (d, J=8,3 Hz, 1H), 8,10-to 7.95 (m, 6H), 7,58 (pseudo t, J=9,2 Hz, 4H), 6,09 (kV, J=6,4 Hz, 1H), 1,59 (d, J=6.5 Hz, 3H)
116HRMS-FAB(m/z)[M+H]+calculated for C30H23F3N4O3, 544,1722; found 544,1722of 174.5-177,58,54 (s, 1H), 8,13 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), of 7.64-of 7.55 (m, 4H), 7,54-7,31 (m, 9H), for 6.81 (s, 1H), 5,97 (kV, J=6,5 Hz, 1H), 1,67 (d, J=6.6 Hz, 3H)
117488 ([M+H]+), 486 ([-H] -)153,5-1568,54 (s, 1H), 8,46 (t, J=1.6 Hz, 1H), 8,12 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.0 Hz, 2H), 7,49 (d, J=8.7 Hz, 2H), 7,44-7,33 (m, 4H), 6,93 (s, 1H), 5,95 (kV, J=6,6 Hz, 1H), of 1.66 (d, J=6,7 Hz, 3H)

118504 ([M+H]+), 502 ([M-H]-)181-184,5to 8.57 (DD, J=2,4, 0.5 Hz, 1H), 8,54 (s, 1H), 8,13 (d, J=8,8 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,68 (DD, J=8,4, 2.5 Hz, 1H), 7,49 (d, J=8.7 Hz, 2H), 7,38 (DD, J=9,1, 0.8 Hz, 2H), 7,37-7,33 (m, 1H), 6.90 to (s, 1H), to 5.93 (q, J=6,6 Hz, 1H), 1,65 (d, J=6,7 Hz, 3H)
119500 ([M+H]+), 498 ([M-H]-)143-1488,54 (s, 1H), 8.34 per-of 8.28 (m, 1H), 8,11 (d, J=8,8 Hz, 2H), 7,78 (d, J=9.1 Hz, 2H), of 7.48 (d, J=8,8 Hz, 2H), 7,42-7,34 (m, 2H), 7,32 (d, J=8.5 Hz, 1H), 7,19 (DD, J=8,6, 2,9 Hz, 1H), 6,94 (s, 1H), 5,93 (kV, J=6,6 Hz, 1H), 3,85 (s, 3H), of 1.66 (d, J=6,7 Hz, 3H)
120(thin film) 3301, 3119, 3061, 2987, 1721, 1596, 1517, 1491, 1439, 1311, 1220, 1163, 1078, 985, 914, 846, 756, 732504 ([M+H]+), 502 ([M-H]-)8,54 (1H), 8,13 (d, J=8,8 Hz, 2H), 7,79 (d, J=9.1 Hz, 2H), 7,66 (t, J=7.8 Hz, 1H), 7,50 (d, J=8,8 Hz, 2H), 7,41-7,35 (m, 2H), 7,32 (d, J=7.5 Hz, 1H), 7,28-7,24 (m, 1H), 6,92 (s, 1H), 5,90 (kV, J=6,7 Hz, 1H), 1,66 (d, J=6,7 Hz, 3H)

121HRMS-FAB(m/z)[M+H]+calculated for C27H25F3N4O3, 510,188; found 510,1876172-1738,54 (s, 1H), 8,14 (d, J=8.7 Hz, 2H), 7,79 (d, J=9.0 Hz, 2H), 7,51 (d, J=8.6 Hz, 2H), 7,38 (DD, J=9,0, 0.7 Hz, 2H), 6.87 in (s, 2H), 6,77 (s, 1H), or 4.31-4,19 (m, 2H), 3,10-of 2.97 (m, 2H), is 2.37 (s, 6H), and 2.26 (s, 3H)
122HRMS-FAB(m/z)[M+H]+calculated for C22H15F3N4O3, 440,109; found 440,110186-188(400 MHz, DMSO-d6) 10,49 (s, 1H), 9,37 (s, 1H), 8,08 (d, J=3,4 Hz, 2H), with 8.05 (d, J=3,7 Hz, 2H), to 7.67 (d, J=8.7 Hz, 2H), to 7.61 (d, J=8.7 Hz, 2H), 7,45 (t, J=7.9 Hz, 2H), 7,32-7,19 (m, 3H)
123HRMS-FAB(m/z)[M+H]+calculated for C22H16F3N5O3, 455,121; found 455,1206219 - 221/td> (300 MHz, DMSO-d6) 10,59 (s, 1H), 9,38 (d, J=0.4 Hz, 1H), 8,39 (d, J=2.7 Hz, 1H), of 8.09 (d, J=2,6 Hz, 2H), of 8.06 (d, J=2,9 Hz, 2H), 7,69-to 7.59 (m, 4H), 7,34 (d, J=8.7 Hz, 1H), 7,07-7,00 (m, 1H), 2.49 USD (s, 3H)
124509 ([M+H]+)153-1688,56 (s, 1H), 8,19 (d, J=8,8 Hz, 2H), 7,80 (d, J=9.1 Hz, 2H), of 7.70 (d, J=8,9 Hz, 1H), 7,63 (d, J=8,1 Hz, 1H), to 7.59 (d, J=8,9 Hz, 2H), 7,45-7,35 (m, 4H), 7,21 (s, 1H)

125509 ([M+H]+)161-1698,56 (s, 1H), 8,19 (d, J=8,8 Hz, 2H), 7,80 (d, J=9.1 Hz, 2H), of 7.70 (d, J=8,9 Hz, 1H), to 7.61 (DD, J=18,0, 8.6 Hz, 3H), 7,40 (DD, J=15,7, 7.7 Hz, 4H), 7,20 (s, 1H)
126509 ([M+H]+)183-1888,56 (s, 1H), 8,19 (d, J=8.7 Hz, 2H), 7,80 (d, J=9.0 Hz, 2H), 7,68 (d, J=8.6 Hz, 2H), EUR 7.57 (d, J=8.6 Hz, 2H), 7,37 (DD, J=15,2, 8,3 Hz, 4H), 7,13 (s, 1H)
127459 ([M+H]+),457 ([M-H] -)184-1888,56 (s, 1H), 8,18 (d, J=8,8 Hz, 2H), 7,80 (d, J=9.1 Hz, 2H), 7,58 (d, J=8.7 Hz, 2H), 7,38 (d, J=9.7 Hz, 2H), 7,29 (DD, J=7,9, 1.5 Hz, 1H), 7,24-7,13 (m, 4H)
128489 ([M+H]+)179-182,58,56 (s, 1H), 8,18 (d, J=8,8 Hz, 2H), 7,80 (d, J=9.1 Hz, 2H), EUR 7.57 (d, J=8.5 Hz, 2H), 7,39 (d, J=8,3 Hz, 2H), 7,25 (d, J=2.4 Hz, 1H), 7,22-7,20 (m, 1H), 7,20-to 7.18 (m, 1H), 7,11 (Shir. s, 1H), to 7.09 (d, J=8.5 Hz, 1H), and 2.26 (s, 3H)

129517 ([M+H]+)172-1808,55 (s, 1H), 8,19 (d, J=8,8 Hz, 2H), 7,80 (d, J=9.1 Hz, 2H), of 7.64-7,56 (m, 4H), 7,46 (square d, J=7,7, 4.5 Hz, 5H), 7,37 (DD, J=12,4, 7,8 Hz, 3H), 7,29 (d, J=8.7 Hz, 1H), 7,20 (DD, J=9,0, 2.4 Hz, 1H), 7,13 (s, 1H)
1All NMR data measured in CDCl3at 300 or 400, unless otherwise specified

Table 2

1. The compound having the following formula:

where:
(a) Ar1represents a substituted phenyl where the above-mentioned substituted phenyl has one Deputy, selected from C1-C6halogenoalkane and C1-C6halogenlampe;
(b) Het is triazolyl;
(c) Ar2represents phenyl;
(d) X1represents O or S;
(e) X2represents About;
(f) R4 represents N or C1-C6alkyl;
(j) n=0, 1, or 2; and
(1) R1, R2 and R3 are independently selected from H, CN, C1-C6of alkyl, C1-C6halogenoalkane,3-C6cycloalkyl, C2-C6alkenyl, C2-C6Alki the sludge, C(=O)O(C1-C6alkyl), phenyl, and Het-1,
where Het-1 is a 5-membered unsaturated heterocyclic ring containing one heteroatom selected from sulfur or oxygen, or 6-membered unsaturated heterocyclic ring containing one nitrogen atom as a heteroatom, and
where Het-1 is optionally substituted by F, Cl, C1-C6the alkyl, C1-C6halogenation or C1-C6alkoxygroup.

2. Connection on p. 1, which has one of the following structures



3. A method of combating insect pests of Lepidoptera or Homoptera, including the application of compounds under item 1 on the seed or plant in a quantity sufficient to deal with such pests.

4. The method according to p. 3, where the insect pest is a well small, well cotton or peach aphid green.

5. A compound selected from


















 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), possessing an activity with respect to cytokines, versions of based on them pharmaceutical compositions and their application. Formula (I) compounds can be applied for treatment or prevention asthma, COPD, ARDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis or gouty arthritis. In general formula (I) L is selected from the group, consisting of -C(O)-, -CH2-, Ar1 represents a mono-, di- or trisubstituted phenyl ring, where substituents are independently selected from the group, consisting of a halogen and -C1-4alkyl; Ar2 represents an optionally substituted thiadiazolyl ring, where the substituent represents -C1-4alkyl, -C3-5cycloalkyl, -methylcyclopropyl, phenyl or a 5- or 6-membered monocyclic heteroaromatic ring or a bicyclic heteroaromatic ring with 9 or 10 atoms, with the said heteroaromatic ring containing 1, 2 or 3 heteroatoms, selected from the group, consisting of S, O and N, where the said phenyl or heteroaromatic ring is optionally mono- or disubstituted with substituents, independently selected from the group, consisting of a halogen, -C1-6alkyl, optionally substituted with 1-4 fluorine atoms, -O-C1-6alkyl, -CF3 and oxo.

EFFECT: increased efficiency of the application of the compounds.

16 cl, 1 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and a method of producing 3,3'-[bis-(1,4-phenylene)]bis-1,3,5-dithiazinanes of formula (1): wherein diphenylenediamine (diaminodiphenylmethane, diaminodiphenyl oxide) reacts with N-tert-butyl-1,3,5-dithiazinane in the presence of a Sm(NO3)3·6H2O catalyst in an argon atmosphere in molar ratio diphenylenediamine: N-tert-butyl-1,3,5-dithiazinane:Sm(NO3)3·6H2O=1:2:(0.03-0.07) at about 20°C in an ethanol-chloroform solvent system (1:1, by volume) for 2.5-3.5 hours.

EFFECT: method of obtaining novel compounds which can be used as antimicrobial and antifungual agents, selective sorbents and extractants of precious metals, special reagents for inhibiting bacterial activity in different process media.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to a method for selective production of 3,3'-[bis-(1,4-phenylene)]bis-1,5,3-dithiazepinanes of formula (1) where R = 4-C6H4-CH2-C6H4-4', 4-C6H4-O-C6H4-4', 4-H3COC6H3-C6H3OCH3-4', where diphenylenediamines (diaminodiphenylmethane, diaminodiphenyl oxide, dimethoxybenzidine) react with 1-oxa-3,6-dithiacycloheptane in the presence of a Sm(NO3)3·6H2O catalyst in an argon atmosphere in molar ratio diphenylenediamine:1-oxa-3,6-dithiacycloheptane:Sm(NO3)3·6H2O=1:2:(0.03-0.07) at about 20°C in an ethanol-chloroform solvent system for 2.5-3.5 hours.

EFFECT: novel method of producing 3,3'-[bis-(1,4-phenylene)]bis-1,5,3-dithiazepinanes, which can be used as antimicrobial, antifungal and anti-inflammatory agents, sorbents and extractants of precious metals and selective complexing agents.

1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 6-substituted isoquinoline and isoquinolinone derivatives of formula or to its stereoisomer and/or tautomer forms and/or a pharmaceutically acceptable salt, wherein R1 represents H, OH or NH2; R3 represents H; R4 represents H, a halogen atom, CN or (C1-C6)alkylene-(C6-C10)aryl; R5 represents H, a halogen atom, (C1-C6)alkyl; R7 represents H, a halogen atom, (C1-C6)alkyl, O-(C1-C6)alkyl; R8 represents H; R9 and R6 are absent; R10 represents (C1-C6)alkyl, (C1-C8)heteroalkyl, (C3-C8)cycloalkyl, (C6)hetrocycloalkyl, (C1-C6)alkylene-(C3-C8)cycloalkyl, (C1-C6)alkylene-(C6-C10)aryl, (C1-C6)alkylene-(C6)heterocycloalkyl; R11 represents H; R12 represents (C1-C6)alkyl, (C3-C8)cycloalkyl, (C5)heteroaryl or (C6-C10)aryl; R13 and R14 independently represent H, (C1-C6)alkyl, (C1-C6)alkylene-R'; n is equal to 0; m is equal to 2 or 3; s is equal to 1 or 2; r is equal to 1; L represents O or NH; R' represents (C3-C8)cycloalkyl, (C6-C10)aryl; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more OCH3; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more halogen atoms; wherein (C1-C8)heteroaryl group means (C1-C8)alkyl groups, wherein at least one carbon atom is substituted by O;. (C6)heterocycloalkyl group means a monocyclic carbon ring system containing 6 ring atoms wherein one carbon atom can be substituted by 1 oxygen atom or 1 sulphur atom which can be optionally oxidated; (C5)heteroaryl means a monoring system wherein one or more carbon atoms can be substituted by 1 nitrogen atom or 1 sulphur atom or a combination of various heteroatoms. Also, the invention refers to using the compound of formula (I) and to a therapeutic agent based on the compound of formula (I).

EFFECT: there are prepared new compounds effective for treating and/or preventing diseases associated with Rho-kinase and/or mediated by Rho-kinase by phosphorylation of myosin light chain phosphatase, and the compositions containing these compounds.

32 cl, 111 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel chromenone derivatives of formula II or its pharmaceutically acceptable salts, where each R20 is hydrogen; R11 is selected from phenyl and 5-6 member saturated or aromatic heterocycle, including one or two heteroatoms, selected from N, O or S, where R11 is optionally substituted with one-two substituents, independently selected from C1-C4alkyl, =O, -O-R13, -(C1-C4alkyl)-N(R13)(R13), -N(R13)(R13), where each R13 is independently selected from hydrogen and -C1-C4alkyl; or two R13 together with nitrogen atom, to which they are bound, form 5-6-member saturated heterocycle, optionally including one additional O, where, when R13 is alkyl, alkyl is optionally substituted with one or more substituents, selected from -OH, fluorine, and, when two R13 together with nitrogen atom, to which they are bound, form 6-member saturated heterocycle, saturated heterocycle is optionally substituted on each carbon atom with -C1-C4alkyl; R12 is selected from phenyl and pyridyl, where R12 is optionally substituted with one or more substituents, independently selected from halogen, C1-C4alkyl, C1-C2 fluorine-substituted alkyl, -O-R13, -S(O)2-R13, -(C1-C4alkyl)-N(R13)(R13), -N(R13)(R13); R14 is selected from hydrogen; and X1 is selected from -NH-C(=O)-†, -C(=O)-NH-†, - -S(=O)2-NH-†, where † stands for place, where X1 is bound with R11; and, when R14 is H; R12is phenyl; and X1 is - C(=O)-NH-†, then R11 is not 1H-pyrazol-3-yl, possessing stimulating activity.

EFFECT: invention relates to pharmaceutical composition based on said compounds, method of treating subject, suffering from or having resistance to insulin, metabolic syndrome or diabetes, as well as to method of increasing sensitivity to insulin.

16 cl, 1 tbl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compounds can find application for preventing or treating cancer, lung cancer, non-small cells lung cancer, small-cell lung cancer, EML4-ALK hybrid polynucleotide-positive cancer, EML4-ALK hybrid polynucleotide-positive lung cancer or EML4-ALK hybrid polynucleotide-positive non-small cells lung cancer. In formula (I) -X-: group of formula , A represents chlorine, ethyl or isopropyl; R1 represents phenyl wherein carbon in the 4th position is substituted by the group -W-Y-Z, and carbon in the 3rd position can be substituted by a group specified in a group consisting of halogen, R00 and -O-R00; R00: lower alkyl which can be substituted by one or more halogen atoms; -W-: a bond, piperidine-1,4-diyl or piperazine-1,4-diyl; -Y- represents a bond; Z represents a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more substitutes R00; R2 represents (i) an optionally bridged saturated C3-10cycloalkyl which can be substituted by one or more groups specified in -N(lower alkyl)2, lower alkyl, -COO-lower alkyl, -OH, -COOH, -CONH-RZB and morpholinyl, or (ii) a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more groups specified in a group consisting of lower alkyl, -CO-lower alkyl, oxo, -CO-RZB and benzene; and RZB: phenyl which can be substituted by a group consisting of halogen and -O-lower alkyl; R3 represents -H.

EFFECT: invention refers to new compounds of formula or their pharmaceutically acceptable salts possessing the properties of a selective inhibitor of EML4-ALK hybrid protein kinase activity.

16 cl, 201 tbl, 582 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to methods of treating or relieving severity of disease in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease. Methods include introduction of effective amount of N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or pharmaceutical composition, containing said compound, to patient.

EFFECT: treatment of relief of disease severity in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease.

16 cl, 15 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazine derivatives represented by general formula (I): 0, where R1 is a hydrogen atom; C1-C6 alkyl; COR5; SO2R5; CO(CH2)mOR6; (CH2)mR6; (CH2)mCONR7R8; (CH2)nNR7R8; (CH2)nOR6; CHR7OR9; (CH2)mR10; m assumes values from 1 to 6; n assumes values from 2 to 6; R2 is phenyl; naphthyl, 1,2,3,4-tetrahydro-naphthalene, biphenyl, phenylpyridine or a benzene ring condensed with a saturated or unsaturated monocyclic heterocycle containing 5-7 atoms and consisting of carbon atoms and 1-4 heteroatoms selected from N, O or S, other than indole, R3 is methyl or ethyl; R4 and R′4 are identical or different and denote a hydrogen atom; a halogen atom; C1-C6 alkyl; NR7R8; SO2Me; as well as stereoisomers, salts and solvates thereof, for therapeutic use and which are capable of inhibiting 11β-HSD1 on an enzymatic and cellular level.

EFFECT: obtaining benzothiazine derivatives.

17 cl, 197 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein A means a six-merous aryl radical or a five-merous heteroaryl radical which contains one heteroatom specified in oxygen and sulphur; one or more hydrogen atoms in the above aryl or heteroaryl radicals can be substituted by substituting groups R1 which are independently specified in a group consisting of: F, Cl, Br, I, (C1-C10)-alkyl-, (C1-C10)-alkoxy-, -NR13R14; B means a radical with mono- or condensed bicyclic rings specified in a group consisting of: six-ten-merous aryl radicals, five-ten-merous heteroaryl radicals and nine-fourteen-merous cycloheteroalkylaryl radicals, wherein cycloheteroalkyl links can be saturated or partially unsaturated, while the heterocyclic groups can contain one or more heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, one or more hydrogen atoms in the radical groups B can be substituted by substituting groups R5 (as specified in the patent claim), L means a covalent bond, X means the group -O-, R2 is absent or means one or more substitutes specified in F and (C1-C4)-alkyl radical; R3 and R4 independently mean (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkylalkyl, (C2-C19)-cycloheteroalkyl, (C3-C19)-cycloheteroalkylalkyl, (C6-C10)-aryl, (C7-C20)-arylalkyl, (C1-C9)-heteroaryl, (C2-C19)-heteroarylalkyl radicals, or R3 and R4 together with nitrogen attached whereto can form a four-ten-merous saturated, unsaturated or partially unsaturated heterocyclic compound which can additionally contain one or more heteroatoms among -O-, -S(O)n-, =N- and -NR8-; other radicals are such as specified in the patient claim. Also, the invention refers to using the compound of formula I for preparing a drug.

EFFECT: compounds of formula (I) as Na+/H+ metabolism inhibitors NHE3.

22 cl, 27 dwg, 1 tbl, 756 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel fungicidally active 5-fluoropyrimidines of general formula I. In compounds of formula , R1 is -N(R3)R4; R2 is -OR21; R3 is: H; C1-C6-alkyl, optionally substituted with 1-3 groups R5; C2-C6-alkenyl, optionally substituted with 1-3 groups R5; a 5- or 6-member heteroaromatic cycle, selected from a group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl; wherein each heteroaromatic cycle is optionally substituted with 1-3 R29 groups; 3H-isobenzofuran-1-oyl; -C(=O)R6; -C(=S)R6; -C(=S)NHR8; -(=O)N(R8)R10; -OR7; -P(O)(OR15)2; -S(O)2R8;-SR8; -Si(R8)3; -N(R9)R10; -(CHR24)mOR29 or -C(=NR16)SR16; where m equals an integer from 1 to 3; R4 is: H; C1-C6-alkyl, optionally substituted with 1-3 R5 groups; or -C(=O)R6; alternatively, R3 and R4 together can form: a 5- or 6-member saturated or unsaturated cycle containing 1-2 heteroatoms selected from N and O, where each cycle can be optionally substituted with 1-3 R11 groups; =C(R12)N(R13)R14 or =C(R15)OR15. The rest of the radicals are given in the claim.

EFFECT: obtaining novel fungicidally active 5-fluoropyrimidines of general formula I.

4 cl, 3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: in general formula A1 stands for CR10R11 or S; A2 stands for CR12R13, C(=O), O, S or S(=O)2; R1 stands for C1-10-alkyl, saturated or unsaturated, branched or non-branched, non-substituted, or monosubstituted, or polysubstituted; C3-10-cycloalkyl or 5- or 6-membered heterocyclyl with the O-atom, each time saturated or unsaturated, non-substituted, or monosubstituted, or polysubstituted; C6-10-aryl or C5-10-heteroaryl with 1-3 heteroatoms, selected from N, O or S, each time non-substituted, or monosubstituted, or polysubstituted; through C1-8-alkyl or C2-8-heteroalkyl bound by the bridge bond C3-10-cycloalkyl, each time saturated, non-substituted, and the alkyl or heteroalkyl chain each time can be branched or non-branched, saturated, non-substituted; or through C1-8-alkyl, bound by the bridge bond aryl or heteroaryl, each time non-substituted, or monosubstituted, or polysubstituted, and the alkyl chain each time can be branched or non-branched, saturated or unsaturated, non-substituted, or monosubstituted, or polysubstituted; R2, R3 and R4 each time independently on each other stand for H; F; Cl; Br; I; methyl; O-C1-6-alkyl or NRaRb, and Ra and Rb together with the nitrogen atom that binds them form heterocyclyl, saturated, non-branched, non-substituted; R5, R6, R7, R8, R10, R11, R12 and R13each time independently on each other stand for H; F; Cl; Br; I; OH or C1-10-alkul; or R5 and R6 or R7 and R11 together with carbon atom(s), that bind(s) them form C3-8-cycloalkyl, each time saturated or non-saturated, non-substituted, or monosubstituted, or polysubstituted; with respective remaining substituents R5, R6, R7, R8, R10, R11, R12 and R13 having the value given above; R9 stands for C3-10-cycloalkyl, saturated, non-substituted; C6-10-aryl or 5- or 6-membered heteroaryl with heteroatom, selected from N and S, each time non-substituted or monosubstituted.

EFFECT: invention relates to substituted nicotinamides of general formula (1), to a medication based on them and their application for treating KCNQ2/3-mediated diseases.

13 cl, 3 tbl, 224 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula (I) , where A is selected from -C(=O)-, -S(=O)2-, and -P(=O)(R5)-, where R5 is selected from C1-6-alkyl, C1-6-alkoxy and hydroxy; B is selected from single bond, -O-, and -C(=O)-NR6-, where R6 is selected from hydrogen; D is selected from single bond, -O-, and -NR9, where R7, R8 and R9 are independently selected from hydrogen; m equals integer number 0-12 and n equals integer number 0-12, where the sum m+n equals 1-20; p equals integer number 0-2; R1 is selected from optionally substituted heteroaryl, where heteroaryl represents aromatic carbocyclic ring, where one carbon atom is substituted with heteroatom; R2 is selected from hydrogen, optionally substituted C1-12-alkyl, and substituents are selected from phenyl, morpholine, halogen and pyridine; C3-12-cycloalkyl, -[CH2CH2O]1-10-C1-6-alkyl); and R3 is selected from optionally substituted C1-12-alkyl, and substituents are selected from morpholine, phenyl, dialkylamine and C3-12-cycloalkyl, optionally substituted with halogen aryl; or R2 and R3 together with adjacent atoms form optionally substituted with alkylcarbonyl or alkyl N-containing heterocyclic or heteroaromatic ring; each of R4 and R4* independently represents hydrogen; and their pharmaceutically acceptable salts, as well as to application of said compounds for treatment of diseases/states, induced by increased level of nicotinamide phosphoribosyltransferase (NAmPRTase).

EFFECT: obtaining novel compounds.

21 cl, 1 dwg, 2 tbl, 83 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein A means morpholinyl, 1,4-oxazepamyl, piperidinyl, pyrrolidinyl or azetidinyl which is bound to N; R1 means C1-C6-alkyl group; R2 means bicyclic aryl group specified in 1H-indolyl, 1H-pyrrolo[3,2-b]pyridyl, quinolyl, naphthyl, 1H-pyrrolo[2,3-b]pyridyl, 5H-pyrrolo[3,2-d]pyrimidinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, benzo[b]thiophenyl, imidazo[1,2-a]pyridyl, benzo[b]thiazolyl, 5H-pyrrolol[2,3-b]pyrazinyl and quinoxalinyl which can be substituted by R4; R3 means hydrogen or halogen atom; R4 means C1-C6-alkyl group, C1-C6-halogenalkyl group, OR1A, halogen, -(CH2)aOH, CN, NHCOR1A, SO2R1A or NHSO2R1A; R5 means C1-C6-alkyl group, -(CH2)aOH, -(CH2)aOR1B, halogen or CONH2; provided p is a plural number, R5 can be identical or different, or R5 can be combined with another R5; each of R1A and R1B independently means C1-C6-alkyl group; a is equal to 0, 1 or 2; n is equal to 1 or 2; p is equal to 0, 1, 2, 3, 4 or 5. Besides, the invention refers to intermediate compounds of formulas (IA) and (IB) for preparing the compounds of formula (I), to a preventive or therapeutic agent containing the compounds of formula (I), pharmaceutical compositions, using the compounds of formula (I) and to a method for preventing or treating diseases.

EFFECT: compounds of formula (I) as selective 5-HT2B receptor antagonists.

11 cl, 1 dwg, 18 tbl, 88 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound of formula [I] or to its pharmaceutically acceptable salt, wherein A represents optionally substituted alkyl, wherein the substitute represents identical or different 1-3 groups specified in aryl optionally substituted by 1-3 groups specified in alkyl, halogen, alkoxy and alkanoyl; cycloalkyl optionally substituted by 1-3 groups specified in alkyl and halogen; hydroxy; alkoxy; halogen; an amino group and oxo; an optionally substituted carbocyclic group specified in a mono- and bicyclic group, wherein an aromatic ring and cycloalkyl are condensed; optionally substituted aryl, an optionally substituted completely saturated 5- or 6-merous monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, wherein the substitute of optionally substituted aryl, the optionally substituted carbocyclic group and the optionally substituted heterocyclic group for A represents identical or different 1-3 groups specified in alkyl, optionally substituted hydroxy, alkoxy, cycloalkyl or halogen; cycloalkyl optionally substituted by alkyl or alkoxy; alkoxy optionally substituted by halogen; halogen; hydroxy; oxo; heterocycle; alkyl sulphonyl; and mono- or dialkylcarbamoyl, optionally substituted amino, wherein the substitute represents identical or different 1 or 2 alkyl or aryl, or optionally substituted carbamoyl, wherein the substitute represents identical or different 1 or 2 alkyls optionally substituted by aryl, X represents optionally substituted methylene or -O-, wherein the substitute of optionally substituted methylene for X represents alkoxy or hydroxy, Q represents N or C-R4, L1 represents a single bond, methylene, -CH=CH-, -O-, -CO-, -NR11-, -NR11CO-, -CONR11- or -CH2NR11-, L2 represents a single bond, -CR6R7- or a bivalent 5- or 6-merous completely saturated monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, R1 and R2 are identical or different, and each represents hydrogen, alkyl or halogen, R3 and R4 are identical or different, and each represents hydrogen, alkyl, alkoxy, cyano or halogen, R1 and R3 are optionally bond thereby forming 5- or 6-merous cycloalkane, or a 5- or 6-merous aliphatic heterocycle containing oxygen atom, R5 represents a carboxyl group, an alkoxycarbonyl group or a bioisosteric group of the carboxyl group, R6 and R7 are identical or different, and each represents hydrogen or alkyl, or R6 and R7 are bond thereby forming cycloalkane, R8 represents hydroxy, alkanoylamino or alkyl sulphonylamino, R9 and R10 represent hydrogen or halogen, and R11 represents hydrogen or alkyl. Besides, the invention refers to specific compounds of formula [I], a drug based on the compound of formula [I], using the compound of formula [I], a method of treating based on using the compound of formula [I], and an intermediate compound of formula [II].

EFFECT: there are prepared new compounds possessing the agonist activity on thyroid hormone β receptor.

18 cl, 36 tbl, 344 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel chromenone derivatives of formula II or its pharmaceutically acceptable salts, where each R20 is hydrogen; R11 is selected from phenyl and 5-6 member saturated or aromatic heterocycle, including one or two heteroatoms, selected from N, O or S, where R11 is optionally substituted with one-two substituents, independently selected from C1-C4alkyl, =O, -O-R13, -(C1-C4alkyl)-N(R13)(R13), -N(R13)(R13), where each R13 is independently selected from hydrogen and -C1-C4alkyl; or two R13 together with nitrogen atom, to which they are bound, form 5-6-member saturated heterocycle, optionally including one additional O, where, when R13 is alkyl, alkyl is optionally substituted with one or more substituents, selected from -OH, fluorine, and, when two R13 together with nitrogen atom, to which they are bound, form 6-member saturated heterocycle, saturated heterocycle is optionally substituted on each carbon atom with -C1-C4alkyl; R12 is selected from phenyl and pyridyl, where R12 is optionally substituted with one or more substituents, independently selected from halogen, C1-C4alkyl, C1-C2 fluorine-substituted alkyl, -O-R13, -S(O)2-R13, -(C1-C4alkyl)-N(R13)(R13), -N(R13)(R13); R14 is selected from hydrogen; and X1 is selected from -NH-C(=O)-†, -C(=O)-NH-†, - -S(=O)2-NH-†, where † stands for place, where X1 is bound with R11; and, when R14 is H; R12is phenyl; and X1 is - C(=O)-NH-†, then R11 is not 1H-pyrazol-3-yl, possessing stimulating activity.

EFFECT: invention relates to pharmaceutical composition based on said compounds, method of treating subject, suffering from or having resistance to insulin, metabolic syndrome or diabetes, as well as to method of increasing sensitivity to insulin.

16 cl, 1 tbl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to piridazine derivatives of formula II

,

in which radicals and symbols have determinations, given in the invention formula, or to their pharmaceutically acceptable salts.

EFFECT: compounds of formula II demonstrate inhibiting effect with respect to proteinkinases such as c-met, ron, or ALK, or chimeric proteins, and can be useful for treatment of disorders, associated with abnormal activity of proteinkinases, such as cancer.

7 cl, 1 tbl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compounds can find application for preventing or treating cancer, lung cancer, non-small cells lung cancer, small-cell lung cancer, EML4-ALK hybrid polynucleotide-positive cancer, EML4-ALK hybrid polynucleotide-positive lung cancer or EML4-ALK hybrid polynucleotide-positive non-small cells lung cancer. In formula (I) -X-: group of formula , A represents chlorine, ethyl or isopropyl; R1 represents phenyl wherein carbon in the 4th position is substituted by the group -W-Y-Z, and carbon in the 3rd position can be substituted by a group specified in a group consisting of halogen, R00 and -O-R00; R00: lower alkyl which can be substituted by one or more halogen atoms; -W-: a bond, piperidine-1,4-diyl or piperazine-1,4-diyl; -Y- represents a bond; Z represents a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more substitutes R00; R2 represents (i) an optionally bridged saturated C3-10cycloalkyl which can be substituted by one or more groups specified in -N(lower alkyl)2, lower alkyl, -COO-lower alkyl, -OH, -COOH, -CONH-RZB and morpholinyl, or (ii) a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more groups specified in a group consisting of lower alkyl, -CO-lower alkyl, oxo, -CO-RZB and benzene; and RZB: phenyl which can be substituted by a group consisting of halogen and -O-lower alkyl; R3 represents -H.

EFFECT: invention refers to new compounds of formula or their pharmaceutically acceptable salts possessing the properties of a selective inhibitor of EML4-ALK hybrid protein kinase activity.

16 cl, 201 tbl, 582 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to methods of treating or relieving severity of disease in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease. Methods include introduction of effective amount of N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or pharmaceutical composition, containing said compound, to patient.

EFFECT: treatment of relief of disease severity in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease.

16 cl, 15 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein A means a six-merous aryl radical or a five-merous heteroaryl radical which contains one heteroatom specified in oxygen and sulphur; one or more hydrogen atoms in the above aryl or heteroaryl radicals can be substituted by substituting groups R1 which are independently specified in a group consisting of: F, Cl, Br, I, (C1-C10)-alkyl-, (C1-C10)-alkoxy-, -NR13R14; B means a radical with mono- or condensed bicyclic rings specified in a group consisting of: six-ten-merous aryl radicals, five-ten-merous heteroaryl radicals and nine-fourteen-merous cycloheteroalkylaryl radicals, wherein cycloheteroalkyl links can be saturated or partially unsaturated, while the heterocyclic groups can contain one or more heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, one or more hydrogen atoms in the radical groups B can be substituted by substituting groups R5 (as specified in the patent claim), L means a covalent bond, X means the group -O-, R2 is absent or means one or more substitutes specified in F and (C1-C4)-alkyl radical; R3 and R4 independently mean (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkylalkyl, (C2-C19)-cycloheteroalkyl, (C3-C19)-cycloheteroalkylalkyl, (C6-C10)-aryl, (C7-C20)-arylalkyl, (C1-C9)-heteroaryl, (C2-C19)-heteroarylalkyl radicals, or R3 and R4 together with nitrogen attached whereto can form a four-ten-merous saturated, unsaturated or partially unsaturated heterocyclic compound which can additionally contain one or more heteroatoms among -O-, -S(O)n-, =N- and -NR8-; other radicals are such as specified in the patient claim. Also, the invention refers to using the compound of formula I for preparing a drug.

EFFECT: compounds of formula (I) as Na+/H+ metabolism inhibitors NHE3.

22 cl, 27 dwg, 1 tbl, 756 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of general formula (I) or pharmaceutically acceptable salts thereof, where Alk is an C1-C6alkyl group; G is C=O and Q is CR51R52 or NR51, where R51 and R52, being identical or different, independently denote H, C1-C6alkyl, optionally substituted with a substitute selected from a group comprising carboxy, phenoxy, benzyloxy, C1-C6alkoxy or hydroxy; C3-C6cycloalkylC1-C6alkyl; phenylC1-C6alkyl, optionally substituted with a halogen; phenylamidoC1-C6alkyl; phenylC1-C6alkylamidoC1-C6alkyl, optionally substituted with a C1-C6alkoxy group; or R51 and R52, together with a carbon atom with which they are bonded form a C=O or C2-C6alkenyl group, optionally substituted with a phenyl; M1 is CR49, where R49 is H; M2 is CR50, where R50 is H; R38 is H, C1-C6alkyl, substituted with a phenoxy group; C3-C6cycloalkylC1-C6alkyl; arylC1-C6alkyl, optionally substituted with 1 or 2 substitutes selected from a group comprising C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxycarbonyl, carboxyl, N-methylamido, hydroxy, C1-C6alkoxyC1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulphanyl, cyano, halogen, perfluoroC1-C6alkyl, nitro, formyl, hydroxyC1-C6alkyl and amino, wherein the aryl moiety is a phenyl or naphthyl; and heteroarylC1-C6alkyl, where the heteroaryl moiety is pyridinyl, optionally substituted with 1 or 2 groups selected from C1-C6alkoxy or hydroxyC1-C6alkyl, pyrazolyl or isoxazolyl, substitute with 1 or 2 C1-C6alkyl groups; R47 and R48 is C1-C6alkyl. The invention also relates to specific compounds, a method of reducing or weakening bitter taste, a composition of a food/non-food product or beverage or drug for reducing or lightening bitter taste and a method of producing a compound of formula (I).

EFFECT: obtaining novel compounds which are useful as bitter taste inhibitors or taste modulators.

37 cl, 6 dwg, 12 tbl, 186 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to a compound of Formula

,

where Y represents a group of formula -(CR9R10)-; X is selected from the group, consisting of -C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and -S(-O)2-; Z represents a group of formula -(CR13R14)q-; R1 is selected from the group, consisting of C1-C12alkyl, optionally substituted with one substituent, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted with a substituent, selected from thienyl, naphthyl and phenyl, with the said phenyl being optionally substituted with 1-2 substituents; selected from halogen, trifluoroalkyl, C1-C6alkyl, methoxy and hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents, selected from halogen, phenyl, amino, phenoxy, C1-C6alkyl, methoxy, hydroxyl and carboxy; and C4-C9heteroaryl, selected from indole, quinoline, quinoxaline, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxin, benzothiasole, pyrazole, furyl and isoxazole, optionally substituted with a substituent, selected from C1-C6alkyl and phenyl; R2 and R3 each is independently selected from the group, consisting of H and C1-C12alkyl; R4a is selected from the group, consisting of H, C1-C12alkyl, optionally substituted with phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15, C(=O)NR15R16, C(=O)OR15, SO2R15 and -C(=NR15)-NR16R17; R4d represents hydrogen or R4a and R4b, taken together with a nitrogen atom, which they are bound to, form an optionally substituted heterocyclic fragment, selected from piperidine, morpholine, pyrrolidine and azetidine, where the substituent is selected from C1-C12alkyl, hydroxy, halogen, carboxy and oxo; each R5a and R5b represents H, or R6, R7 and R8 each is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6-C10aryl, optionally substituted with halogen, or taken together with a carbon atom, which they are bound to, two or more of R6, R7 and R8 form a fragment, selected from the group, consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted with C1-C6alkyl; C6aryl, optionally substituted with 2 substituents, selected from halogen; each R9 and R10 represents H or C1-C12alkyl, substituted with naphthyl; each R11 and R12 represents H; R13 and R14 represent H, or each R15, R16 and R17 is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6aryl, substituted with one substituent, selected from C1-C6alkyl; and C5-heteroaryl, additionally containing one nitrogen atom, with the said heteroaryl representing pyridyl; q represents an integer number, selected from the group, consisting of 2, 3 and 4; r represents 1; or its pharmaceutically acceptable salt. The invention also relates to particular compounds of 1,4-diazepan-2-one derivatives.

EFFECT: obtaining 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists.

21 cl, 7 tbl, 110 ex

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