Herbicides for weeds resistant to sulfonylurea-base herbicide, method for control of weeds resistant to sulfonylurea-base herbicide, compounds

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes a herbicide against weeds resistant to sulfonylurea-base herbicide and comprising compound of the formula (I):

wherein Q represents condensed heterocyclic group of the formula (Q1), (Q3), (Q4) given in the invention description; X represents lower alkyl or lower alkoxyl group; Y represents lower alkoxyl group. Invention describes compound of the formula (II):

wherein R1 represents halogen atom or optionally halogenated lower alkyl group; R2 represents hydrogen atom; R3 represents (C2-C4)-alkyl group or lower cycloalkyl group; X represents lower alkyl group or lower alkoxyl group; Y represents lower alkoxyl group. Also, invention describes herbicides comprising compounds of the formula (II) and a method for control of weeds resistant to sulfonylurea-base herbicide. Method involves applying herbicide comprising compound of the formula (I) or compound of the formula (II). Herbicide is used for control of weeds resistant to sulfonylurea-base herbicide in rice-paddy fields.

EFFECT: valuable properties of herbicides.

10 cl, 8 tbl, 69 ex

 

The invention relates to a new herbicide containing condensed heterocyclic compound sulfonylureas, to a method of weed control in rice plantations and to the new condensed heterocyclic compound sulfonylureas. In particular, this invention relates to herbicide, which when applied to seedlings of paddy rice during or after planting has excellent selectivity to the seedlings of paddy rice and effectively kills weeds resistant to herbicides based on sulfonylurea, to a method of weed control, herbicide-based sulfonylureas, by its application, and to the new condensed heterocyclic compound sulfonylureas.

Prior art

Up to the present time in practical use was a huge amount of sulfonylurea compounds for plantations, paddy rice, and they were used widely and, as a rule, in the form of a combined preparation comprising two or more active ingredient, representing different types of herbicides and grass weeds that are effective against the weeds of cereal family, but in recent years emerged weeds resistant to herbicides based on sulfonylureas, such as benzylbromide, perezoso Horonite and imazosulfuron, and fight with them becomes problematic.

It is known that weeds resistant to herbicides based on sulfonylureas, generally have cross-resistance to inhibitors acetolactate (ALS), including herbicides on the basis of sulfonylureas, acting on ALS. However, traditional methods of weed control are the ways to add active ingredients effective against weeds that are resistant to herbicides based on sulfonylurea, to the existing combined drug, thereby increasing the amount of active ingredients in the combined preparation for weed control (for example, JP-A 10-287513, JP-A 11-228307 and JP-A 11-349411). Under these circumstances there is a need to herbicides that have a satisfactory effect on weeds that are resistant to herbicides based on sulfonylurea, and is able to reduce the number of active ingredients in the combination product.

The purpose of the invention

The purpose of this invention to provide an herbicide that is perfectly destroys weeds resistant to herbicides based on sulfonylureas, without damaging herbicide seedlings of paddy rice, and which can reduce the number of active ingredients in the combination product. Another purpose of this invention is the development of gerbic is Yes, perfectly destroys not only the weeds that are resistant to herbicides based on sulfonylureas, but also annual broadleaf weeds and perennial weeds, non-resistant weeds, and which has a wide range of actions, without any herbicide damage to seedlings of paddy rice.

Summary of invention

To develop excellent herbicides with a broad spectrum of action on weeds and reduce herbicide damage protected culture, the applicants of the present invention conducted extensive research and found that the compounds represented by the following formula (I)or their salts, although falling within the scope of condensed sulfonylurea compounds described in JP-A 64-38091 filed by the authors of the present invention are more effective herbicide action on a wider range of herbicide-resistant on the basis of sulfonylurea weeds in comparison with most other herbicides, and through this was accomplished the present invention.

It has been unexpectedly found that the compounds of the following formula (I), where the substituent Q is a group represented by Q1-Q3, compounds where R3 represents hydrogen, show high herbicide effects on weeds, sensitivity is entrusted to herbicides based on sulfonylureas, but significantly reduce their effect on weeds that are resistant to these herbicides, whereas these compounds where R3 is any of the following groups of substituents, and Q is a group represented by Q4, possess a highly effective herbicide effect not only on the weeds that are sensitive to herbicides based on sulfonylureas, but also on weeds that are resistant to these herbicides.

Thus, the present invention relates to

(1) the herbicide to weeds, herbicide on the basis of sulfonylureas, including a connection (also hereinafter referred to as compound (I)represented by the formula:

where Q is a condensed heterocyclic group represented by the formula:

where R1 represents a hydrogen atom, a halogen atom, a cyano, a nitro-group, optionally halogenated lower alkyl group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, amino group, lower alkylamino or lower dialkylamino,

R2 represents a hydrogen atom, halogen atom or optionally halogenated lower alkyl group,

R3 present is employed, a halogen atom, a cyano, a nitro-group, optionally halogenated lower alkyl group, optionally halogenated or substituted lower alkyl lower cycloalkyl group, optionally halogenated lower alkenylphenol group, optionally halogenated lower alkylamino group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, amino group, lower alkylamino or lower dialkylamino,

X and Y are the same or different, and each represents an optionally halogenated lower alkyl group, optionally halogenated lower CNS group or halogen atom, or its salt;

(2) the herbicide, according to the above (1), where R1 represents a halogen atom, optionally halogenated lower alkyl group, lower allylthiourea, lower alkylsulfonyl group or lower alkylsulfonyl group, R3 represents a halogen atom, optionally halogenated lower alkyl group, optionally halogenated or substituted lower alkyl lower cycloalkyl group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkyls fanilow group, the lower alkylamino or lower dialkylamino, and X and Y each represent an optionally halogenated lower CNS group;

(3) the herbicide, according to the above item (1), where R1 represents a halogen atom or an optionally halogenated lower alkyl group, R2 represents a hydrogen atom, R3 represents a halogen atom, optionally halogenated lower alkyl group, optionally halogenated or substituted lower alkyl lower cycloalkyl group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, a lower alkylamino or lower dialkylamino, and X and Y each represent an optionally halogenated lower alkyl group or optionally halogenated lower CNS group;

(4) the herbicide, according to the above item (1), where Q is a condensed heterocyclic group represented by the above formula Q1 or Q4;

(5) the compound represented by the formula:

where R1 represents a halogen atom or an optionally halogenated lower alkyl group, R2 represents a hydrogen atom, R3 represents not battelino halogenated C 2-4alkyl group or optionally halogenated or substituted lower alkyl lower cycloalkyl group, and X and Y each represent an optionally halogenated lower alkyl group or optionally halogenated lower CNS group, or its salt (also hereinafter referred to as compound (Ia));

(6) the compound according to the above item (5), where R1 represents a halogen atom, R3 represents a C2-4alkyl group or a lower cycloalkyl group, and X and Y each represent a methoxy group, or its salt;

(7) herbicide for weeds resistant to the herbicide on the basis of sulfonylureas, including the compound described in the above item (5), or its salt;

(8) herbicide for weeds resistant to the herbicide on the basis of sulfonylureas, including the compound described in the above item (6)or its salt;

(9) the herbicide on any of the above items(1)-(4), (7) and (8), which has a significant effect on the weeds, herbicide on the basis of sulfonylurea;

(10) method of weed control, herbicide on the basis of sulfonylureas, which includes applying a herbicide that is described in any of the above items(1)-(4), (7) and (8); and

(11) method of weed control in the fields of paddy rice, which vkluchennosti herbicide on any of the above items (1)to(4), (7) and (8); and similar.

Detailed description of the invention

Given the term ″lower″ a lower alkyl group, lower alkenylphenol group, lower CNS group, the lower allylthiourea etc. in this description denotes a hydrocarbon fragment consists of 1 or 2-6 carbon atoms, preferably from 1 or 2-4 carbon atoms. Hydrocarbon fragment includes, for example, linear or branched C1-6alkyl group, a C2-6alkenylphenol group1-6CNS group1-6allylthiourea etc.

In condensed heterocyclic group represented by Q in compound (I), R1 represents a hydrogen atom, a halogen atom, a cyano, a nitro-group, optionally halogenated lower alkyl group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, amino group, lower alkylamino or lower dialkylamino.

″halogen Atom″represented by R1 includes, for example, fluorine, chlorine, bromine, iodine, etc

″a Lower alkyl group″represented by R1 includes, for example, linear or branched C1-4alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc. ″Halogen″ is ″ optionally halogenated lower alkyl group″ includes, for example, fluorine, chlorine, bromine, iodine, etc. and the lower alkyl group may be substituted by 1 or more, preferably 1 to 3 halogen atoms, in positions where you may have substituents.

″Lower CNS group″represented by R1 includes a linear or branched C1-4CNS group, such as methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy etc. ″Halogen″ ″optionally halogenated lower CNS group″ include the same halogen as in the above-described lower alkyl group and lower CNS group may be substituted by 1 or more, preferably 1 to 3 halogen atoms, in positions where you may have substituents.

″Lower alkyl″ ″lowest allylthiourea″, ″lower alkylsulfonyl group″, ″lower alkylsulfonyl group″, ″lowest alkylamino″ and ″lowest dialkylamino″represented by R1, includes the same group as in the case of the above ″lower alkyl groups″.

R2 represents a hydrogen atom, halogen atom or optionally halogenated lower alkyl group, with the ″halogen atom″, ″halogen″ and ″a lower alkyl group″ illustrated by examples, to provide the Lenna above for R1, and the lower alkyl group may be substituted by 1 or more, preferably 1 to 3 halogen atoms, in positions where you may have substituents.

R3 represents a halogen atom, a cyano, a nitro-group, optionally halogenated lower alkyl group, optionally halogenated or substituted lower alkyl lower cycloalkyl group, optionally halogenated lower alkenylphenol group, optionally halogenated lower alkylamino group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, amino group, lower alkylamino or lower dialkylamino. ″halogen Atom″, ″halogen″, ″a lower alkyl group″ and ″lower CNS group″ illustrated by the examples presented above for R1. The lower alkyl group and lower CNS group may be substituted by 1 or more, preferably 1 to 3 halogen atoms, in positions where you may have substituents. ″Lower cycloalkyl group″ includes cyclopropyl, cyclobutyl etc. ″lower Alchemilla group″ includes ethynyl, 1-propenyl, 2-propenyl, 1,2-PROPADIENE, 1-butenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl etc. and ″lower quinil″ includes ethinyl 1-PROPYNYL, 2-PROPYNYL, 1-butynyl, 2-butynyl etc. ″lowest allylthiourea″, ″lower alkylsulfonyl group″, ″lower alkylsulfonyl group″, ″lowest alkylamino″ and ″lowest dialkylamino″ ″a lower alkyl group″ illustrated by examples ″lower alkyl groups″ R1 described above.

As a condensed heterocyclic group represented by Q, preferred are represented by the formula Q1, imidazo[1,2-b]pyridazinone group represented by the formula Q3 pyrazolo[1,5-a]pyrimidine group and represented by the formula Q4 pyrazolo[1,5-b]thiazole group, due to their high activity against weeds resistant to herbicides based on sulfonylureas. The group represented by formula of Q1, is especially preferred.

In compound (I) X and Y are the same or different and each represents an optionally halogenated lower alkyl group, optionally halogenated lower CNS group or halogen atom. ″Halogen″, ″a lower alkyl group″, ″lower CNS group″ and ″halogen atom″ illustrated by the examples presented above R1. Lower alkyl group or lower CNS group may be substituted by 1 or more, predpochtitel is about 1 to 3 halogen atoms, in the provisions, which may have substituents. As X and Y, it is preferable to optionally halogenated lower CNS group, and more preferred is a methoxy group.

As compounds (I), preferred is a compound where Q represents Q1 and (a) R1 represents a halogen atom or an optionally halogenated lower alkyl group, R2 represents a hydrogen atom, halogen atom or optionally halogenated lower alkyl group, R3 represents a halogen atom, optionally halogenated lower alkyl group, optionally halogenated or substituted lower alkyl lower cycloalkyl group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, a lower alkylamino or lower dialkylamino, and X and Y each represent optionally halogenated lower alkyl group or optionally halogenated lower CNS group; more preferred is a compound where Q represents Q1 and (b) R1 represents a halogen atom or an optionally halogenated lower alkyl group, R2 represents a hydrogen atom, R3 is a halo atom is s, optionally halogenated lower alkyl group, optionally halogenated or substituted lower alkyl lower cycloalkyl group, optionally halogenated lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, lower alkylsulfonyl group, a lower alkylamino or lower dialkylamino, and X and Y each represent an optionally halogenated lower CNS group; and particularly preferred is a compound where Q represents Q1 and (c) R1 represents a halogen atom, R2 represents a hydrogen atom, R3 represents a C2-4alkyl group or a lower cycloalkyl group, and X and Y each represent a methoxy group, such as compound (Ia).

Typical examples of compound (I) include:

(1) compound (I), where Q represents Q1, R1 represents ethyl, R2 represents a hydrogen atom, R3 represents a methylthio and X and Y each represent a methoxy,

(2) compound (I), where Q represents Q1, R1 represents methyl, R2 represents a hydrogen atom, R3 represents ethyl, and X and Y each represent a methoxy,

(3) compound (I), where Q represents Q1, R1 represents methyl, R2 represents a hydrogen atom, R3 represents these is thio and X and Y each represent methoxy,

(4) compound (I), where Q represents Q1, R1 represents methyl, R2 represents a hydrogen atom, R3 represents a methylthio and X and Y each represent a methoxy,

(5) compound (I), where Q represents Q2, R1 represents methyl, R2 represents ethoxy and X and Y each represent a methoxy,

(6) the compound (I), where Q represents the Q3, R1 represents methyl, R2 represents a hydrogen atom, R3 represents methoxy, and X and Y each represent a methoxy,

(7) the compound (I), where Q represents the Q3, R1 represents methyl, R2 represents a hydrogen atom, R3 represents ethoxy and X and Y each represent a methoxy,

(8) the compound (I), where Q represents Q4, R1 represents methylsulphonyl and X and Y each represent a methoxy,

(9) the compound (I), where Q represents Q1, R1 represents methyl, R2 represents a hydrogen atom, R3 represents n-propyl and X and Y each represent a methoxy,

(10) the compound (I), where Q represents Q1, R1 represents a chlorine atom, R2 represents a hydrogen atom, R3 represents ethyl, and X and Y each represent a methoxy,

(11) the compound (I), where Q represents Q1, R1 represents a chlorine atom, R2 PR is dstanley a hydrogen atom, R3 represents n-propyl and X and Y each represent a methoxy,

(12) compound (I), where Q represents Q1, R1 represents methyl, R2 represents a hydrogen atom, R3 represents isopropyl and X and Y each represent a methoxy,

(13) the compound (I), where Q represents Q1, R1 represents a chlorine atom, R2 represents a hydrogen atom, R3 represents isopropyl and X and Y each represent a methoxy,

(14) the compound (I), where Q represents Q1, R1 represents a chlorine atom, R2 represents a hydrogen atom, R3 represents cyclopropyl and X and Y each represent methoxy and

(15) compound (I), where Q represents Q1, R1 represents a fluorine atom, R2 represents a hydrogen atom, R3 represents n-propyl and X and Y each represent methoxy.

The compound (I) may be in the form of optical isomers, diastereomers and/or geometric isomers and the invention includes such isomers and mixtures thereof.

Acid groups, such as alphagraph, carboxyl group, etc. in groups of substituents in the molecule of the compound (I) can form agrokhimichesky acceptable basic salts with inorganic base, organic base, etc. and the basic nitrogen atoms in the molecule and major groups, such as aminokislot the e group, in groups of substituents may form agrokhimichesky acceptable additive salt of the acid with an inorganic acid, organic acid, etc. Inorganic basic salts include, for example, salts with alkali metals (e.g. sodium, potassium etc), alkaline earth metals (e.g. calcium, etc. and ammonium, etc. and organic basic salts include salts with, for example, dimethylamine, triethylamine, N,N-dimethylaniline, piperazine, pyrrolidine, piperidine, pyridine, 2-phenethylamine, benzylamino, ethanolamine, diethanolamine, 1,8-diazabicyclo[5.4.0]undecene (further abbreviated as DBU), etc. Additive salts of inorganic acid compounds (I) include salts with, for example, hydrochloric acid, Hydrobromic acid, itestosterone acid, sulfuric acid, nitric acid, phosphoric acid, perchloro acid, etc. and additive salt of organic acid compounds (I) include salts with, for example, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, p-toluensulfonate acid, methanesulfonic acid, triperoxonane acid, etc.

The compound (I) can be obtained by a method described, for example, in JP-A 64-38091, and the specific method shown in the following examples.

When connected to the e (I) is in crystalline form, the compound (I) shows crystalline polymorphism or pseudocrystalline polymorphism depending on the conditions of crystallization, the compound (I), even having a chemical structure that gives the same spectrum of nuclear magnetic resonance, can give a different range of infrared absorption. This invention covers not only the crystalline forms of compound (I)showing a crystal polymorphism and pseudocrystalline polymorphism, but also its mixed crystals.

When applied to seedlings of paddy rice, especially during or after planting, the compound (I) or its salt has an excellent selectivity towards the seedlings of paddy rice and effectively kills weeds resistant to herbicides based on sulfonylureas.

When the compound (I) or its salt is used as a pesticide, particularly herbicide, it can be used in conventional agrochemical form, that is, in the form of formulations, such as, for example, emulsion, oil, aerosol, hydrate, powder, DL (not loose) powder, granules, fine particles, fine agent F, a flowing agent, a dry flowing medium, large granules, tablets, etc. by dissolving or suspending one or more compounds (I) or their salts in a suitable liquid carrier, depending on the intended use, or smesi the I with suitable solid carriers or adsorbing them on appropriate solid media. These formulations can optionally be mixed with an emulsifier, a dispersant, a substance that increases the wetting ability, a wetting agent, a humectant, a thickener and stabilizer, and can be prepared by a method that is essentially known.

Used carrier liquid (solvent), preferably is a solvent, such as, for example, water, alcohols (e.g. methanol, ethanol, 1-propanol, 2-propanol, ethylene glycol and so on), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, onomatology ether of ethylene glycol, onomatology ether of diethylene glycol, onomatology ether of propylene glycol, etc.), aliphatic hydrocarbons (e.g. kerosene, fuel oil, machine oil and so on), aromatic hydrocarbons (e.g. benzene, toluene, xylene, ligroin solvent, methylnaphthalene, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride and so on), acid amides (e.g. dimethylformamide, dimethylacetamide, etc.), esters (e.g. ethyl acetate, butyl acetate, esters of fatty acids and glycerol, etc.), NITRILES (e.g. acetonitrile, propionitrile etc) and so on, and these solvents can be used alone or as a mixture in suitable proportions. Solid carriers (diluents and napolnitel which include vegetable powders (for example, soybean powder, tobacco powder, wheat flour, wood flour etc.), mineral powders (e.g. clays such as kaolin, bentonite, acid clay and clay, talcum powder, such as talcum powder and the powder agalmatolite, silica, such as diatomaceous earth and mica powder, aluminum oxide, powdered sulfur, activated carbon, etc. and these substances can be used individually or as a mixture in suitable proportions. The liquid carrier or solid carrier can be used in an amount usually from about 1 to 99 wt.%, preferably, about 1 to 80 wt.%, based on the total mass of the formulation.

If you want to use a surfactant as an emulsifier, a substance that increases the wetting ability of wetting agent, dispersant, etc. it is possible to use nonionic and anionic surfactants, such as Soaps, alcylaryl esters of polyoxyethylene (for example, Neugen™EA 142™ (TM: registered trademark, etc.; produced by Dai-ichi Kogyo Seiyaki Co., Ltd.), complex aryl esters of polyoxyethylene (e.g., Nonal™produced by Toho Chemical Co., Ltd.), the alkyl sulphates (for example, Yumal 10™, Yumal 40™manufactured by Kao Corporation), alkyl sulphonates (e.g., Neogen™, Neogen T™produced by Dai-ichi Kogyo Seiyaki Co., Ltd.; Neopelex™, stitches is by Kao Corporation), ethers of polyethylene glycol (e.g., Nonipol 85™, Nonipol 100™, Nonipol 160™produced by Sanyo Chemical Industries, Ltd.) and esters of polyhydric alcohols (for example, Tween 20™Tween 80™manufactured by Kao Corporation). Surfactants can be used in an amount usually from about 0.1 to 50 wt.%, preferably, from about 0.1 to 25 wt.%, based on the total mass of the formulation.

The content of the compound (I) or its salt in the herbicide, preferably, is from about 1 to 90 wt.% in the emulsion, hydrate, etc., from about 0.01 to 10 wt.% oil, powder, DL (psypokes) powder and from about 0.05 to 10 wt.% in fine agent F and granules, but depending on the intended use concentration may be appropriately changed. Emulsion, hydrate and similar appropriately diluted (e.g., 100-100000 times) with water or a similar solvent in the case of using sputtering.

When the compound (I) or its salt is used as a herbicide, its amount varies depending on the scope, period of application, method of application, type of weeds grown products and so on, but usually the amount of active ingredient (compound (I) or its salt) is from about 0.05 to 50 g, preferably from about 0.1 to 5 g/ar field paddy rice or the ome from 0.04 to 10 g, preferably, from about 0.08 to 5 g/ar field.

For use on weeds in the fields of compound (I) or its salt is preferably used as tools for soil treatment before emergence or processing of stems, leaves and soil. For example, the herbicides of the present invention can be safely used even after 2-3 weeks without the development of any herbicide damage.

The herbicide containing the compound (I) or its salt of the present invention, can be applied simultaneously with one or more (preferably 1-3) other herbicides, plant growth regulators, bactericides, insecticides, acaricides, nematicides, etc. if necessary. In addition, the herbicide according to this invention can be used in a mixture with one or more (preferably 1-3) other herbicides, plant growth regulators, bactericides, insecticides, acaricides, nematicides and similar drugs. Other herbicides (herbicide active ingredients include, for example, (1) herbicides based on sulfonylureas (chlorsulfuron, sulfometuron, chloroaromatic, triasulfuron, amidosulfuron, oxasulfuron, tribenuronmethyl, prosulfuron, ethanesulfonate, triflusulfuron, thifensulfuron, flazasulfuron, rimsulfuron, nicosulfuron, flupyrsulfuron, enculturated, pyrazosulfuron, imazosulfuron, sulfosulfuron, chinaculture, azimsulfuron, metsulfuron, halosulfuron, ethoxysulfuron, cycloaliphatic, iodosulfuron, etc.), (2) pyrazol herbicides (perflourinated, pyrazolate, paradoxien, benzefoam etc.), (3) urethane herbicides (Vallat, butyl, triallate, phenmedipham, chlorpropham, Azul, fenazepam, benthiocarb, molinet, asbroker, perimutter, timepart, swap etc.), (4) herbicides based chloroacetanilide (propachlor, metazachlor, alachlor, acetochlor, metolachlor, butachlor, pretilachlor, tanishlar etc.), (5) herbicides based on diphenyl ether (acifluorfen, oscillogram, lactofen, fomesafen, klonipin, gametocidal, bifenox, CNP, etc.), (6) herbicides based on triazine (Simazine, atrazine, propazine, cyanazine, ametryn, simetryn, deltamethrin, prometryn etc.), (7) herbicides based on proximity or benzoic acid (2,3,6-TBA, dicamba, quinclorac, quinmerac, clopyralid, picloram, triclopyr, fluroxypyr, benazolin, dichloromethyl, fluazifop, galaxytool, quizalofop, chalufour, 2,4-RA, MCP, MSRV, finacial etc.), (8) herbicides based on amide or urea (isoxaben, diflufenican, Diuron, linuron, fluometuron, Difenoxin, maildaemon, Isoproturon, Sauron, tebuthiuron, methabenzthiazuron, propanil, mefenacet, clomipram, e.g. anilide, bromobutyl, dameron, cumyluron, etamesonic, oxazalone etc.), (9) organic phosphorus-containing herbicides (glyphosate, bialaphos, amiprophosmethyl, anilofos, bensulide, piperophos, butamifos, anilofos etc.), (10) herbicides based on dinitroaniline (bromoxynil, ioxynil, dinoseb, trifluralin, prodiamine etc.), (11) herbicides based cyclohexandione (aloxide, sethoxydim, chloroxygen, clethodim, cycloxydim, tralkoxydim, etc.), (12) herbicides based on imidazoline (imazamethabenz, imazapyr, imazamethabenz, imazethapyr, imazamox, imazaquin etc.), (13) herbicides based on bipyridine (paraquat, Diquat etc.), (14) other herbicides (bentazon, tridiphane, indianian, amitrol, carfentrazone, sulfentrazone, fehlerraten, phentramin, isoxaflutole, clomazone, maleic hydrazide, peridot, ozone chloride, norflurazon, pyrithiobac, bromacil, terbacil, metribuzin, oxacyclobutane, cinmetacin, flamelurker, tendonitis, flumioxazin, platesetter, azafenidin, beforethat, oxadiazon, oxadiargyl, phenoxazone, chalapati, cafestol, PerkinElmer, bispyribac sodium, perbenzoic, piritramid, phentramin, indianian, ACN, benzamycin, dithiopyr, dalapon, chlorine etc) and so on

The plant growth regulators (active ingredients that regulate the growth of plants) include, for example, hymexazol, paclobutrazol uniconazole-P, invented, prohexadione calcium etc. Bactericides (antibacterial active ingredients include, for example, (1) bactericides based on POLYHALOGENATED compounds (Captan, etc.), (2) organophosphorus bactericides (IBP, EDDP, cyclophosphates etc.), (3) benzimidazole bactericides (benomyl, carbendazim, thiophanate etc.), (4) carboxamide bactericides (mepronil, flutolanil, leflunomid, parameter, telital, pencycuron, cropropamide, diclocil etc.), (5) acylalanines bactericides (metalaxyl, etc.), (6) azole bactericides (triflumizole, ipconazole, perforated, prochloraz etc.), (7) bactericides based on ethoxyacrylate acid (AZOXYSTROBIN, metamyosyn etc.), (8) bactericides, representing antibiotics (validamycin And, blasticidin S, kasugamycin, polyoxin etc.), (9) other bactericides (phtalic, provenzal, isoprothiolane, tricyclazole, pyroquilon, verison, acibenzolar S-methyl, declomycin, oxolinic acid, fenesin oxide, TPN, iprodion etc), etc. Insecticides (insecticide active ingredients include, for example, (1) organophosphorus insecticides (fenthion, fenitrothion, pirimiphosmethyl), diazinon, quinalphos, isoxathion, predatation, chlorpyrifos, vamidothion, Malathion, pentat, dimethoat, disulfoton, monocrotophos, tetrachlorvinphos, chlorfenvinfos, propafol, Arafat, trichlorfon, EPN, feasts is Orthos etc), (2) urethane insecticides (carbaryl, metolcarb, isoprocarb, VRMS, propoxur, CMS, carbofuran, carbosulfan, benfuracarb, furathiocarb, methomyl, thiodicarb, etc.), (3) synthetic PYRETHROID insecticides (cicloprofen, etofenprox etc.), (4) nereistoxin insecticides (cartap, bensultap, thiocyclam etc.), (5) neonicotinoid insecticides (Imidacloprid, nitenpyram, acetamiprid, thiamethoxam, thiacloprid, dinotefuran, clothianidin etc.), (6) other insecticides (buprofezin, tebufenozide, fipronil, ethiprole etc. and so the Acaricides (acaricide active ingredients include, for example, hexythiazox, pyridaben, fenpyroximate, tebufenpyrad, chlorfenapyr, etoxazole, pyrimidifen etc. Nematicides (nematocide active ingredients include, for example, fosthiazate etc. Such further agrochemical active ingredients (for example, herbicide active ingredients, active ingredients, regulating plant growth, antibacterial active ingredients of insecticidal active ingredients, acaricide active ingredients, nematocide active ingredients, etc. can be used in amounts, usually from about 0.1 to 20 wt.%, preferably, from about 0.1 to 10 wt.%, based on the total mass of the preparation.

Herbicides containing the compound (I) or its salt of the present invention, when neo is the divergence can be mixed with synergists (e.g., piperonylbutoxide etc), stimulants (e.g., eugenol etc), repellents (e.g., creosote, etc.), dyes (for example, Food Blue No. 1 and so on) and fertilizers (e.g. urea and so on).

Examples

Further, the present invention is described in more detail by reference to examples (examples of the synthesis of intermediate compounds), examples, synthesis examples of drugs and test examples, but the invention is not limited to them.

As a solution for elution in the column chromatography in the reference examples and the examples of synthesis using solvent used for the analysis of TLC (thin layer chromatography). For TLC analysis using silikagelevye plates for TLC 60F254manufactured by Merck, and to determine using a UV detector. As silica gel for column using silica gel 60 (0,063 to 0,200 mm), manufactured by Merck. When the solvent for elution using a mixed solvent, the bulk composition of the mixture of solvents is shown in brackets.

Spectra of proton nuclear magnetic resonance (1H NMR) recorded on the following instruments : Bruker AC-200P (200 MHz) and Bruker AV-400 (400 MHz) with tetramethylsilane was as an internal standard, and all Delta values are shown in ppm Spectra of nuclear magnetic resonance of fluorine (19F NMR) is registryroot spectrometer Bruker AC-200P (188 MHz) and Bruker AV-400 (376 MHz) using ferrichloride as an internal standard, and all Delta values are shown in ppm

Spectra of infrared absorption (IR) register spectrometer model Perkin-Elmer Paragon 100 FT-IR, and the position of the absorption bands are shown as wave numbers (cm-1). The melting temperature measured by the device for measuring the melting temperature trace Yanagimoto.

Abbreviations used in the reference examples, examples of the synthesis and the tables have the following meanings: Me: methyl group, Et: ethyl group, n-Pr: normal through the group, I-Pr: isopropyl group, t-Pr: cyclopropyl group, n-Bu: normal bucilina group, ISO-Bu: isobutylene group, TMS: trimethylsilyl group, s: singlet, d: doublet, t: triplet, q: Quartet, usher.: broad, m: multiplet, DD: doublet of doublets, dt: doublet of triplets, TT: triplet of triplets, DQC: doublet of quartets, TCEs: a triplet of quartets, user. from: broadened singlet, J: the constant of spin-spin splitting, CDCl3: heavy chloroform, DMSO-d6: heavy dimethyl sulfoxide, Tpl.: melting point, decomp.: decomposition, Hz: Hertz, THF: tetrahydrofuran, DMF: N,N-dimethylformamide, dffp: 1,3-bis(diphenylphosphino)propane.

Reference example 1

Synthesis of 6-ethyl-2-methylimidazo[1,2-b]pyridazine

6-Chloro-2-methylimidazo[1,2-b]pyridazin (5,00 g, to 29.8 mmol) and dichloride, [1,3-bis(diphenylphosphino)propane]is ikela (II) (0.08 g, 0.15 mmol) is suspended in a mixture of dry ether (40 ml) and dry THF (20 ml) and then stirred while cooling in an ice bath, during which the mixture for 5 minutes, added dropwise a solution of ethylmagnesium in ether (3 M, 15 ml, 45 mmol) (internal temperature 10°or lower). The temperature of the reaction solution was increased to room temperature and the mixture is stirred at the same temperature for 2 hours and boiling under reflux for 3 hours. The reaction solution while continuing to stir, cooled to room temperature and to it in small pieces add water (30 ml). Next, the reaction mixture was stirred at room temperature and pH adjusted to approximately 5-6 with concentrated hydrochloric acid. Organic and aqueous layers are separated from each other and the aqueous layer was extracted with ethyl acetate (70 ml·2). The organic layers are combined and washed with water (250 ml·3). The organic layer is dried over magnesium sulfate and concentrating, the residue is purified column chromatography on silica gel (chloroform:ethyl acetate = 2:1→1:1), the resulting crude oily substance additionally purified column chromatography on silica gel (ethyl acetate) and get listed in the title compound as a pale red oily substance. The output is equal to 1.32 g (27.4 per cent).

1H NMR (CDCl3, #x003B4; ): of 1.33 (3H, t, J=7.5 Hz), 2,48 (3H, s), 2,82 (2H, q, J=7.5 Hz), 6.87 in (1H, d, J=9,2 Hz), the 7.65 (1H, s), 7,72 (1H, d, J=9,2 Hz).

IR (pure, cm-1): 2973, 2934, 2876, 1543, 1460, 1382, 1333, 1300, 1263, 1155, 1125, 1057, 1000, 820, 726, 699.

Reference example 2

Synthesis of 6-ethyl-2-methylimidazo[1,2-b]pyridazin-3-ralfinamide

6-Ethyl-2-methylimidazo[1,2-b]pyridazin (2.70 g, and 16.7 mmol) dissolved in 1,2-dichloroethane (30 ml), to this solution, with stirring, at room temperature added chlorosulfonic acid (1.27 g, 18.5 mmol) and the mixture refluxed with stirring for 5 hours. Then the reaction solution is cooled to about 70°and within 1 minute to it dropwise added triethylamine (2.38 g, 23.5 mmol). After adding dropwise, the reaction solution is refluxed under stirring for 20 minutes. After that, the reaction solution is cooled to about 70°and to him within 1 minute added dropwise phosphorus oxychloride (3,86 g of 25.2 mmol). After adding dropwise, the mixture is refluxed with stirring for 2 hours. The reaction solution is allowed to cool to about 50°and poured into 50 ml of warm water (about 50°). The mixture is stirred for 5 minutes and the organic layer separated. The aqueous layer was extracted with chloroform (50 ml·2). The organic layers are combined, washed with water, dried over magnesium sulfate and concentrated. The residue is dissolved in acetonitrile (40 ml), to this solution add 14N aqueous ammonia (7 ml) under stirring at room temperature and the mixture is stirred at room temperature for 2 hours. After the reaction finished, the reaction solution is poured into a mixture of ice water (150 ml) and the pH adjusted to about 4 with concentrated hydrochloric acid, and receiving crystals, which are then collected by filtration, washed with water and dried under reduced pressure. After that, the crystals purified column chromatography on silica gel (chloroform:acetone = 9:1→4:1). Specified in the title compound obtained as white crystals. Yield 1.8 g (44,7%).

Tpl.=215,0-215,5°

1H NMR (DMSO-d6that δ): of 1.30 (3H, t, J=7.5 Hz), to 2.57 (3H, s), with 2.93 (2H, q, J=7.5 Hz), 7,39 (1H, d, J=9.3 Hz), 7,47 (2H, user. C)8,08 (1H, d, J=9,3 Hz).

IR (nujol, cm-1): 3304, 3177, 3090, 1546, 1540, 1507, 1463, 1389, 1362, 1341, 1309, 1201, 1166, 1127, 1086, 1057, 959, 900, 864, 824, 772, 686, 670, 652, 591, 525.

Reference example 3

Synthesis of 2-chloro-6-n-propylimidazol[1,2-b]pyridazine

2,6-Dichloroimidazo[1,2-b]pyridazin (1.6 g, 8.5 mmol), dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) (catalytic amount) and anhydrous tetrahydrofuran (20 ml) was placed in a 100-ml three-neck flask under nitrogen atmosphere and stirred at the OHL is a discussion on an ice bath, and to this mixture is added dropwise at a temperature of 10°With or below the add solution propylaniline in tetrahydrofuran (2M, 6.4 ml, 12.8 mmol). After the addition the mixture is stirred for 1 hour at the same temperature, for 1 hour at room temperature and for 2 hours at a temperature of from 50 to 60°C. After the reaction finished, the reaction solution is allowed to cool, added water (50 ml), the mixture is stirred and extracted with ethyl acetate (20 ml·2). The organic layers are combined, washed with water, dried over magnesium sulfate, concentrated and the residue purified column chromatography on silica gel (hexane:ethyl acetate = 2:1), obtaining mentioned in the title compound as orange crystals (containing a small amount of impurities). The output is 0.8 g (48,2%).

Tpl.: not measured

1H NMR (CDCl3that δ): a 1.01 (3H, t, J=7,3 Hz), 1,7-1,9 (2H, m), and 2.79 (2H, t, J=7,6 Hz), of 6.96 (1H, d, J=9.3 Hz), of 7.75 (1H, d, J=9.3 Hz), 7,80 (1H, s).

Reference example 4

Synthesis of 2-chloro-6-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

2-Chloro-6-n-propylimidazol[1,2-b]pyridazin (0.8 g, 4.1 mmol) and dichloroethane (10 ml) is placed in a 200-ml flask with a form of eggplant, stirred at room temperature and to this mixture is added chlorosulfonic acid (0.54 g, 4.5 mmol) in one portion and the mixture is boiled with inverse x is Hladilnika under stirring for 4 hours. The reaction solution is cooled to about 70°With him one portion add triethylamine (0.5 g, 5 mmol) and stirred to dissolve the solids, then the solution in one portion add phosphorus oxychloride (0,79 g, 5 mmol) and the mixture refluxed with stirring for 2 hours. After completion of the reaction, the reaction solution is allowed to cool, added water (50 ml) and the organic phase is separated. The organic phase is washed with saturated salt solution, dried over magnesium sulfate, concentrated, to the residue add acetonitrile (10 ml) and 28% aqueous ammonia (4 ml) and stirred at room temperature for 2 hours. After completion of the reaction to the reaction solution was added water (100 ml), adjusted pH to about 2 with diluted hydrochloric acid and the resulting crystals are collected by filtration, washed with water, chloroform and dried under reduced pressure, obtaining mentioned in the title compound as light brown crystals. The output is the 0,49 g (43,5% for stage 3).

Tpl.=174-175°

1H NMR (DMSO-d6that δ)as 0.96 (3H, t, J=7.4 Hz), 1,7-1,9 (2H, m), 2.8 to 3.0 (2H, m), 7,53 (1H, d, J=9.5 Hz), 7,82 (2H, user. C), 8,19 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3377, 3324, 3189, 1545, 1364, 1322, 1187, 1166, 821, 680, 597.

Reference example 5

Synthesis of 6-n-butyl-2-chloroimidazo[1,2-b]pyridazine

Zinc chloride (2,04 g, 15.0 mmol) is dried at 180°C for 2 hours in vacuum, then cooled to room temperature and to it add anhydrous tetrahydrofuran (20,0 ml). To the mixture for about 30 minutes dropwise while cooling in an ice bath, add n-utility (1.6 M, 9.0 ml, 14.4 mmol) and stirred for 30 minutes under cooling in an ice bath, receiving saline (n butylzinc in tetrahydrofuran. Separately in a nitrogen atmosphere to prepare a suspension of 2,6-dichloroimidazo[1,2-b]pyridazine (1.88 g, 10.0 mmol) dichloride and [1,3-bis(diphenylphosphino)propane]Nickel (II) (0.16 g, 0.30 mmol) in anhydrous tetrahydrofuran (20,0 ml) and thereto within 30 minutes added dropwise the previously prepared solution of chloride of n-butylzinc in tetrahydrofuran, the temperature of which is supported at 3-6°C. the Mixture is stirred for 15 minutes under cooling in an ice bath for 3 hours at room temperature then poured into a saturated solution of salt and pH adjusted to 2 with diluted hydrochloric acid. The reaction solution is extracted twice with ethyl acetate, the extracts combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (ethyl acetate:hexane = 1:4), getting mentioned in the title compound as pale yellow crystals. The output is the 2,03 g 96,8%).

Tpl.=61,0-63,0°

1H NMR (CDCl3that δ)as 0.96 (3H, t, J=7,3 Hz)of 1.41 (2H, TCEs, J=7,5, 7,3 Hz)of 1.73 (2H, TT, J=7,8, 7.5 Hz), of 2.81 (2H, t, J=7.8 Hz), of 6.96 (1H, d, J=9.4 Hz), 7,74 (1H, d, J=9.4 Hz), 7,79 (1H, s).

IR (nujol, cm-1): 3115, 3061, 1545, 1466, 1378, 1326, 1276, 817.

Reference example 6

Synthesis of 6-n-butyl-2-chloroimidazo[1,2-b]pyridazin-3-ralfinamide

6-n-Butyl-2-chloroimidazo[1,2-b]pyridazin (1,00 g, 4.77 mmol) was dissolved in chloroform (10.0 ml) and to this solution, with stirring, dropwise at room temperature added chlorosulfonic acid (0.35 ml, at 5.27 mmol). After boiling the mixture under reflux for 5 hours TLC confirm that remained of the original material, so it adds an extra amount of chlorosulfonic acid (0.35 ml, at 5.27 mmol) and the mixture refluxed for 4 hours. The resulting suspension is allowed to cool to room temperature, add triethylamine (2,50 ml of 17.9 mmol) and phosphorus oxychloride (2.00 ml, 21.5 mmol) and the mixture is again refluxed for 4 hours. The reaction solution is cooled to room temperature, poured into water and extracted 3 times with chloroform, the extracts are combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, getting 3,24 g of a dark red liquid. This liquid races is varaut in acetonitrile (10.0 ml) and added dropwise to a solution of 25% ammonia water (5,00 g, of 73.5 mmol) in acetonitrile (15.0 ml) under cooling in an ice bath. The mixture is stirred for 30 minutes under cooling in an ice bath and for 1 hour at room temperature and then the acetonitrile is distilled off under reduced pressure. Bring pH balance to 2 with diluted hydrochloric acid and twice extracted with chloroform, the chloroform layers are combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (ethyl acetate:hexane = 1:1→chloroform:ethanol = 20:1), obtaining mentioned in the title compound as white crystals. The output is equal to 0.92 g (66,8%).

Tpl.=165,5-KZT 166.5°

1H NMR (DMSO-d6that δ): 0,93 (3H, t, J=7,3 Hz)to 1.37 (2H, TCEs, J=7,5, and 7.3 Hz), 1,72 (2H, TT, J=7,9 7,5 Hz), with 2.93 (2H, t, J=7.9 Hz), 7,53 (1H, d, J=9.4 Hz), 7,80 (2H, s), 8,18 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3412, 3360, 3287, 3197, 1546, 1464, 1376, 1321, 1172.

Reference example 7

Synthesis of N'-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine

N,N-diisobutylamine (5,44 g, 34.5 mmol) dissolved in chloroform (25,0 ml), cooled in a bath of a mixture of ice - sodium chloride and to this solution are added dropwise phosphorus oxychloride (3,22 ml, 34.5 mmol) at -2°With or below. After stirring the mixture at a temperature of -2°or lower within 30 minutes there was added 2,6-di is laronidase[1,2-b]pyridazin-3-ylsulphonyl (x 6.15 g, 23,0 mmol). After stirring the mixture at -10°within 10 minutes to the solution for 20 minutes at a temperature of 5°or lower dropwise added triethylamine (19.3 ml, 138 mmol). The mixture is stirred for 1 hour at 0°or lower and for 1 hour at room temperature, then poured into aqueous saturated sodium bicarbonate solution and extracted 5 times with chloroform. The extracts are combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (ethyl acetate:hexane = 1:1), obtaining mentioned in the title compound as pale yellow crystals. The output is equal to 5.58 g (59,6%).

Tpl.=151,0-154,0°

1H NMR (CDCl3that δ): 0,76 (6N, d, J=6,7 Hz), 0,97 (6N, d, J=6,7 Hz), 1,90-2,10 (2H, m), 3,23 (2H, d, J=7,6 Hz), or 3.28 (2H, d, J=7,7 Hz), 7,26 (1H, d, J=9.5 Hz), of 7.90 (1H, d, J=9.5 Hz), 8,51 (1H, s).

IR (nujol, cm-1): 1615, 1456, 1324, 1311, 1146, 910, 858, 654.

Reference example 8

Synthesis of N'-(2-chloro-6-cyclopropylamino[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine

The magnesium metal powder (0.27 g, 11.1 mmol) is mixed with iodine (5 mg), heated desiccant in a nitrogen atmosphere, cooled to room temperature and to this mixture is added anhydrous tetrahydrofuran (15.0 ml). To the mixture, stir at room temperature, dropwise add Aut cyclopropylboronic (1,33 g, 1.10 mmol), maintained at a temperature of from 28 to 33°S, and then the mixture is stirred at room temperature for 30 minutes, obtaining a pale yellowish-gray solution cyclopropylmagnesium in tetrahydrofuran. Separately, in anhydrous tetrahydrofuran (10.0 ml) under nitrogen atmosphere was dissolved zinc chloride (1.50 g, 11.0 mmol), dried at 180°C for 4 hours in vacuum, and then incubated at 0°or lower in a bath of ice and sodium chloride, for which to this solution is added dropwise the previously prepared solution of cyclopropylmagnesium in tetrahydrofuran. The mixture is stirred at about -10°C for 15 minutes and the resulting suspension in the form of powder added dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) (0.27 g, 0.50 mmol) and then to this mixture is added dropwise a solution of N'-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine (2,03 g, 5.00 mmol)dissolved in dry tetrahydrofuran (10.0 ml). The mixture was stirred at -10°C for 2 hours, then at room temperature for 16 hours then poured into aqueous saturated solution of salt, bring the pH to 2 with diluted hydrochloric acid and extracted 4 times with chloroform. The extracts are combined, dried over anhydrous magnesium sulfate, concentrated under reduced pressure and the residue purified speaker chromatogra what s on silica gel (ethyl acetate:hexane = 1:1), whereby regenerate 0.64 g (31.5 per cent) of the original N'-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine and also get mentioned in the title compound as pale yellow crystals. The output is equal to 0.94 g (45,7%).

Tpl.=154,0-160,0°

1H NMR (CDCl3that δ): 0,74 (6N, d, J=6,7 Hz), 0,95 (6N, d, J=6,7 Hz), 1,00-1,10 (2H, m), 1,10-1,25 (2H, m), 1.85 to 2,10 (2H, m), 2,10-of 2.20 (1H, m), 3,19 (2H, d, J=7.5 Hz), or 3.28 (2H, d, J=7.5 Hz), 6,98 (1H, d, J=9,4 Hz), 7,78 (1H, d, J=9.4 Hz), to 8.45 (1H, s).

IR (nujol) ν (see-1): 1613, 1464, 1334, 1318, 1143, 909, 859, 661.

Reference example 9

Synthesis of N'-(2-chloro-6-etherimide[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 8, except that instead of the solution of cyclopropylmagnesium in tetrahydrofuran use a solution of commercially available vinylmania in tetrahydrofuran and dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) is used in an amount of 3 mol.% relative to the source of N'-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine. The output is the 80,4%.

Tpl.=194,0-198,0°

1H NMR (CDCl3that δ): 0,71 (6N, d, J=6,7 Hz), 0,94 (6N, d, J=6.6 Hz), 1.85 to 2,10 (2H, m), 3,17 (2H, d, J=7.5 Hz), 3,26 (2H, d, J=7,7 Hz), 5,77 (1H, d, J=11,1 Hz), 6,16 (1H, d, J=17,8 Hz), PC 6.82(1H, DD, J=17,8 and 11.1 Hz), 7,46 (1H, d, J=9.5 Hz), 7,89 (1H, d, J=9.5 Hz), and 8.50 (1H, s).

IR (nujol, cm-1): 1614, 1456, 1350, 1319, 1145, 913, 859, 664, 612.

Reference example 10

Synthesis of N'-(2-chloro-6-(1-propenyl)imidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine

Specified in the title compound obtained as a mixture of E - and Z-isomers (E:Z=5:3) as pale-yellow crystals by the same reaction as in reference example 8, except that instead of the solution of cyclopropylmagnesium in tetrahydrofuran use a solution of commercially available 1-propanimidamide in tetrahydrofuran, and dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) is used in an amount of 3 mol.% relative to the source of N'-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine. The output is 100%.

Tpl.: not measured, because the E and Z in the mixture.

1H NMR (CDCl3that δ): [E isomer] 0,72 (6N, d, J=6.6 Hz), 0,94 (6N, d, J=6.6 Hz), 1.85 to 2,10 (2H, m), from 2.00 (3H, DD, J=6,9, 1.5 Hz), 3,17 (2H, d, J=7,6 Hz), 3,26 (2H, d, J=7,7 Hz), 6,51 (1H, DQC, J=16,0, 1.5 Hz), of 6.71 (1H, DQC, J=16,0, 6.9 Hz), 7,35 (1H, d, J=9.5 Hz), 7,82 (1H, d, J=9.5 Hz), and 8.50 (1H, s).

1H NMR (CDCl3that δ): [Z isomer] 0,72 (6N, d, J=6.6 Hz), 0,92 (6N, d, J=6.6 Hz), 1.85 to 2,10 (2H, m), of 2.21 (3H, DD, J=7,3, 1.8 Hz), 3,12 (2H, d, J=7.5 Hz)at 3.25 (2H, d, J=7,7 Hz), 6,23 (1H, DQC, J=11,9, and 7.3 Hz), 6,40 (1H, DQC, J=11,9, 1.8 Hz), 7,19 (1H, d, J=9.5 Hz), the 7.85 (1H, d, J=9.5 Hz), 8,43 (1H, s).

IR (nujol, cm-1): 1609, 1456, 131, 1319, 1144, 911.

Reference example 11

Synthesis of N'-(2-chloro-6-aminimides[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine

a) N'-(2-chloro-6-(trimethylsilylethynyl)imidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine obtained as pale-yellow crystals by the same reaction as in reference example 8, except that instead of the bromide solution cyclopropylamine in tetrahydrofuran use a solution trimethylsilylacetamide lithium in tetrahydrofuran, and dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) is used in an amount of 3 mol.% relative to the source of N'-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine. The output is equal to 32.9 per cent.

Tpl.=180,0-182,0°C.

1H NMR (CDCl3that δ): 0,30 (N, C)0,73 (6N, d, J=6,7 Hz), 0,97 (6N, d, J=6.6 Hz), 1.85 to 2,10 (2H, m), 3,24 (2H, d, J=7,6 Hz), with 3.27 (2H, d, J=7,7 Hz), 7,30 (1H, d, J=9.4 Hz), 7,86 (1H, d, J=9.4 Hz), 8,56 (1H, ).

IR (nujol, cm-1): 1614, 1455, 1339, 1314, 1302, 1140, 914, 864, 839.

(b) N'-(2-chloro-6-(trimethylsilylethynyl)imidazo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine (2,31 g, 4,63 mmol) is dissolved in a solvent mixture of tetrahydrofuran-water (10:1) and to the solution with stirring under cooling in an ice bath, add a hydrate of tetrabutylammonium fluoride (1.50 g, 5,04 mmol). After stirring the mixture for 20 min while cooling in an ice bath and then it is carbonated shall return distilled off under reduced pressure and the residue is dissolved in ethyl acetate. The ethyl acetate solution washed twice with water, dried over anhydrous magnesium sulfate, concentrated to dry under reduced pressure, obtaining mentioned in the title compound as pale yellow crystals. The output is a 1.96 g (100%).

Tpl.=166,0-167,5°C.

1H NMR (DMSO-d6that δ): 0,68 (6N, d, J=6.6 Hz), 0.88 to (6N, d, J=6.6 Hz), 1.85 to 2,10 (2H, m), 3,19 (2H, d, J=7,6 Hz)to 3.33 (2H, d, J=7,6 Hz), 4,94 (1H, s), to 7.68 (1H, d, J=9.4 Hz), 8,30 (1H, d, J=9.4 Hz), to 8.45 (1H, ).

IR (nujol, cm-1): 3270, 2120, 1613, 1453, 1347, 1332, 1316, 1147, 870, 664.

Reference example 12

Synthesis of 2-chloro-6-cyclopropylamino[1,2-b]pyridazin-3-ralfinamide

N'-(2-chloro-6-cyclopropylamino[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine (0,93 g of 2.26 mmol) dissolved in dioxane (9,00 ml) and to this solution with stirring, added dropwise 36% concentrated hydrochloric acid (9.0 ml, 107 mmol) at 100°C. the Mixture is stirred for 15 hours at a temperature of from 100 to 105°C, then allowed to cool to room temperature and concentrate under reduced pressure to the formation of crystals. To the residue is added water (30 ml) and the crystals are completely settled, then filtered off, washed with water and methanol, getting mentioned in the title compound as white crystals. The output is 0.31 g (50.4 percent).

Tpl.=194,0-196,0°C.

H NMR (DMSO-d6that δ): 1,10-1,25 (4H, m), 2,30 at 2.45 (1H, m), of 7.36 (1H, d, J=9.4 Hz), 7,78 (2H, user. C)to 8.12 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3348, 3247, 1553, 1468, 1455, 1358, 1316, 1170, 908, 825, 662.

Reference example 13

Synthesis of 2-chloro-6-etherimide[1,2-b]pyridazin-3-ralfinamide

Carry out the same reaction in the same manner as in reference example 12, except that instead of N'-(2-chloro-6-cyclopropylamino[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine use N'-(2-chloro-6-etherimide[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine. The resulting crystals purified column chromatography on silica gel (chloroform:methanol = 10:1), obtaining mentioned in the title compound as white crystals. The output is equal to 42.1%.

Tpl.=229,0-233,0°C.

1H NMR (DMSO-d6that δ): by 5.87 (1H, d, J=11.2 Hz), 6,50 (1H, d, J=17,9 Hz)6,86 (1H, DD, J=17,9, 11.2 Hz), 7,89 (2H, s), of 7.96 (1H, d, J=9.6 Hz), compared to 8.26 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3316, 3183, 1466, 1368, 1321, 1167.

Reference example 14

Synthesis of (E)-2-chloro-6-(1-propenyl)imidazo[1,2-b]pyridazin-3-ralfinamide

The reaction is carried out in the same manner as in reference example 12, except that instead of N'-(2-chloro-6-cyclopropylamino[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine use N'-(2-chloro-6-(1-propenyl)imide is zo[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine in the form of a mixture of E and Z. The resulting crystals purified column chromatography on silica gel (chloroform:methanol = 20:1), obtaining mentioned in the title compound as white crystals. The output is equal to 70.1%.

Tpl.=225,0-229,0°C.

1H NMR (DMSO-d6that δ): up to 1.98 (3H, DD, J=6,8, 1.7 Hz), of 6.71 (1H, DQC, J=16,0, 1.7 Hz), 7,01 (1H, DQC, J=16,0, 6,8 Hz), 7,83 (2H, s), to 7.84 (1H, d, J=9.5 Hz), 8,19 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3323, 3179, 1662, 1550, 1466, 1360, 1325, 1173.

Reference example 15

Synthesis of 2-chloro-6-(2-chloranil)imidazo[1,2-b]pyridazin-3-ralfinamide

The reaction is carried out in the same manner as in reference example 12, except that instead of N'-(2-chloro-6-cyclopropylamino[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine use N'-(2-chloro-6-aminimides[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine. The resulting crystals purified column chromatography on silica gel (ethyl acetate:hexane = 1:1), obtaining the E - and Z-isomers indicated in the title compound as white crystals. Exit E-isomer equal to 7.5%, and the output of the Z-isomer is equal to 72.4%.

Physical characteristics of the E-isomer:

Tpl.>240°C (decomp.).

1H NMR (DMSO-d6that δ): 7,37 (1H, d, J=13,8 Hz), 7,82 (1H, d, J=9.6 Hz), to $ 7.91 (1H, d, J=13,8 Hz), to 7.93 (2H, user. C)8,29 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3329, 3182, 1616, 1467, 1361, 1324, 1169, 945.

Physically the characteristics of the Z-isomer:

Tpl.=197,0-200,0°C.

1H NMR (DMSO-d6that δ): 7,14 (1H, d, J=8,3 Hz), 7,20 (1H, d, J=8,3 Hz), 7,83 (2H, user. C)of 8.06 (1H, d, J=9.6 Hz), with 8.33 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3370, 3260, 1632, 1465, 1364, 1308, 1187, 1164, 842.

Reference example 16

Synthesis of 2-chloro-6-aminimides[1,2-b]pyridazin-3-ralfinamide

N'-(2-chloro-6-aminimides[1,2-b]pyridazin-3-ylsulphonyl)-N,N-diisobutylamine (792 mg, 2.00 mmol) suspended in dioxane (10.0 ml) and to the suspension with stirring dropwise at room temperature is added 28% aqueous ammonia (4,00 g, 65,8 mmol). The mixture is stirred at room temperature for 3 days, then concentrated to remove the ammonia, and the pH adjusted to 1 with concentrated hydrochloric acid. The reaction solution was diluted with water and extracted with ethyl acetate, the extract is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (ethyl acetate:hexane = 1:1), obtaining mentioned in the title compound as pale yellow crystals. The output is 71 mg (13.8 per cent).

Tpl.>234°C (decomp.).

1H NMR (DMSO-d6that δ): to 4.92 (1H, s), of 7.69 (1H, d, J=9.4 Hz), 8,02 (2H, user. C), 8,32 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3359, 3294, 3242, 2123, 1464, 1356, 1312, 1170.

Reference example 17

Synthesis of 2-chloro-6-n-propylimidazol[1,2-b]pyridazin the

2,6-dichloroimidazo[1,2-b]pyridazin (10.0 g, 53.2 mmol) and dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) (0,43 g, 0.80 mmol) are added to a tetrahydrofuran (80,0 ml) under nitrogen atmosphere and the mixture under cooling in an ice bath for 60 minutes added dropwise a solution of bromide n-Propylamine in tetrahydrofuran (2M, 31.9 per ml, to 63.8 mmol). The mixture is stirred for 10 minutes, cooling in an ice bath, the reaction mixture is heated to room temperature and stirred for 2 hours at room temperature. To the reaction mixture was added with cold water (700 ml), then acidified with concentrated hydrochloric acid, the precipitated solid is collected by filtration, the insoluble solid is washed with diluted hydrochloric acid and then with water. On the one hand, the filtrate is extracted with ethyl acetate, the extracts are combined and washed with diluted hydrochloric acid, saturated salt solution, aqueous saturated sodium bicarbonate solution and saturated saline solution in this order. The resulting organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated. The concentrated residue and the solid is collected by filtration, purified column chromatography on silica gel (ethyl acetate:hexane = 3:7), receiving specified in zag is lowke connection in the form of white crystals. The output is of 9.21 g (88.5 percent).

Tpl.=73,9-80,0°

1H NMR (CDCl3that δ): a 1.01 (3H, t, J=7.4 Hz), of 1.78 (2H, m), and 2.79 (2H, t, J=7,6 Hz), of 6.96 (1H, d, J=9.3 Hz), of 7.75 (1H, d, J=9.3 Hz), 7,80 (1H, s).

IR (nujol, cm-1): 3122, 1466, 1377, 1314, 1302.

Reference example 18

Synthesis of 2-chloro-6-isobutylamides[1,2-b]pyridazine

The reaction is carried out in the same manner as in reference example 17, except that instead of a solution of bromide n-Propylamine in tetrahydrofuran use a solution of bromide isobutylamine in tetrahydrofuran. The resulting crude product is purified column chromatography on silica gel (ethyl acetate:hexane = 1:4), getting mentioned in the title compound as pale yellow crystals. The output is equal to 1.27 g (60,6%).

Tpl.=71,0 is 72.5°

1H NMR (CDCl3that δ): 0,98 (6N, d, J=6.6 Hz), is 2.09 (1H, m), 2,68 (2H, d, J=7,3 Hz)6,94 (1H, d, J=9.3 Hz), of 7.75 (1H, d, J=9.3 Hz), 7,81 (1H, s).

IR (nujol, cm-1): 3126, 3059, 1545, 1466, 1369, 1331, 1320, 1279, 803.

Reference example 19

Synthesis of 2-chloro-6-isobutylamides[1,2-b]pyridazin-3-ralfinamide

The reaction is carried out in the same manner as in reference example 6, except that instead of 2-chloro-6-n-butylimido[1,2-b]pyridazine use of 2-chloro-6-isobutylamides[1,2-b]pyridazin. The resulting reaction mixture cleanse the column chromatography on silica gel (ethyl acetate:hexane = 1:1), getting listed in the title compound as white crystals. The output is equal to 1.12 g (64,0%).

Tpl.=168,0-169, 5mm°

1H NMR (DMSO-d6that δ): 0,93 (6N, d, J=6.6 Hz), and 2.14 (1H, m), 2,82 (2H, d, J=7,4 Hz), 7,51 (1H, d, J=9.4 Hz), 7,80 (2H, s), 8,19 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3316, 3180, 3117, 1548, 1469, 1362, 1336, 1321, 1200, 1173, 849, 678.

Reference example 20

Synthesis of 2-chloro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl

2-Chloro-6-n-propylimidazol[1,2-b]pyridazin (of 5.00 g, 25.6 mmol) dissolved in 1,2-dichloroethane (30,0 ml) and to this solution at room temperature added chlorosulfonic acid (3,40 ml of 51.1 mmol). The mixture is refluxed for 8.5 hours, then cooled to room temperature and to it was added triethylamine (7,84 ml, 56.2 mmol) and phosphorus oxychloride (5,24 ml, 56.2 mmol) and refluxed for 4 hours. To the reaction mixture add the cold water and the mixture is then extracted with chloroform. The extracts are combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The concentrated residue is purified column chromatography on silica gel (ethyl acetate:hexane = 3:7), receiving specified in the title compound as pale yellow crystals. The output is the yield of 7.40 g (98.4 per cent).

Tpl.=94,2-95,5°

1H NMR (CDCl3that δ): of 1.06 (3H, t, J=7.4 Hz), a 1.88 (2H, m) to 2.99 (2H, t, J=7,6 Hz), was 7.36 (1H, d, J=9.4 Hz), 7,95 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 1464, 1436, 1386, 1314, 1166, 620, 573, 562, 550.

Reference example 21

Synthesis of 2-fluoro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl

Dry potassium fluoride (7.30 g, 130 mmol), 18-crown-6 (1,33 g of 5.03 mmol) and 2-chloro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl (7,40 g of 25.2 mmol) is refluxed in DMF (100 ml) for 3 hours and then left overnight at room temperature. The reaction mixture was concentrated under reduced pressure, to the concentrated residue add the cold water and the mixture is then extracted with chloroform. The extracts are combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The concentrated residue is purified column chromatography on silica gel (ethyl acetate:hexane = 3:7), receiving 5,28 g of a mixture containing unreacted starting material. Then dry potassium fluoride (7.30 g, 130 mmol), 18-crown-6 (1.22 g, 4.61 mmol) and 5,28 g of the reaction mixture is refluxed in DMF (50,0 ml) for 5 hours and then stirred at 150°With during the night. The reaction mixture is cooled, concentrated under reduced pressure, to the concentrated residue add the cold water and the mixture is then extracted with chloroform. The extracts are combined, dried over anhydrous self the volume of magnesium, filtered, concentrated and the concentrated residue is purified column chromatography on silica gel (ethyl acetate:hexane = 3:7), receiving specified in the title compound as white crystals. The output is 2,02 g (30.7 per cent).

1H NMR (CDCl3that δ): of 1.05 (3H, t, J=7,3 Hz), of 1.85 (2H, m), 2,95 (2H, t, J=7,7 Hz), 7,37 (1H, d, J=9.4 Hz), to 7.93 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 1538, 1434, 1310, 1240, 1220, 1188, 799, 765, 695, 613, 595.

Reference example 22

Synthesis of 2-fluoro-6-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

(a) 2-Fluoro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl (1,00 g, a 3.83 mmol) was diluted with acetonitrile (20,0 ml), to this mixture is added a solution of sodium hydroxide (0,23 g of 5.75 mmol) in water (8.0 ml) and stirred at room temperature for 4 hours. Since the reaction does not go to the end, add a further quantity of sodium hydroxide (0.08 g, 2.00 mmol) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, concentrated to residue water is added and then the mixture is acidified with concentrated hydrochloric acid. To the concentrated residue add acetone and the insoluble solid is removed by filtration, the filtrate is concentrated under reduced pressure, getting 1.18 g of a yellowish brown oily the substances, containing 2-fluoro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl acid.

(b) an Oily substance (1.18 g)containing 2-fluoro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl acid, dissolved in 1,2-dichloroethane (5.0 ml), to this solution at room temperature is added phosphorus oxychloride (0,70 ml, 7,66 mmol) and the mixture refluxed for 4 hours. Since the reaction does not go to the end, to the mixture an additional amount of phosphorus oxychloride (0,70 ml, 7,66 mmol) and the mixture refluxed for 2 hours. The reaction mixture is cooled, add cold water and then extracted with chloroform. The extracts are combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The concentrated residue was diluted with acetonitrile (2.0 ml), added dropwise to a solution of 28% ammonia water (8.0 ml) in acetonitrile (5.0 ml) under cooling in an ice bath and stirred for 3 hours at room temperature. The reaction mixture was diluted with water and then acidified dropwise adding concentrated hydrochloric acid. The precipitated solid is collected by filtration, washed with water and the solid is purified column chromatography on silica gel (acetone:chloroform = 2:5), receiving specified in the title compound as yellowish white crystals. Output is equal to 0.33 g (33.4 per cent).

Tpl.=147,8-148,0°

1H NMR (DMSO-d6that δ): 0,97 (3H, t, J=7.4 Hz), of 1.76 (2H, m), 2,89 (2H, t, J=7,7 Hz), 7,56 (1H, d, J=9.4 Hz), to 7.84 (2H, s), 8,19 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3318, 1540, 1465, 1412, 1351, 1305, 1170, 609.

19F NMR (DMSO-d6that δ): -114,3.

Reference example 23

Synthesis of 2-ethylthio-6-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

Sodium hydride (60%, 0.73 g, 18.2 mmol) suspended in DMF (10.0 ml) under cooling in an ice bath, to this suspension is added dropwise ethanthiol (1.35 ml, 18.2 mmol) and the mixture was stirred at 0°C for 2 hours. To this mixture is added 2-chloro-6-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl (1,00 g of 3.64 mmol) and heated at 110°C for 2.5 hours with stirring. The reaction mixture is allowed to cool, diluted with water and acidified dropwise adding concentrated hydrochloric acid. The precipitated solid is collected by filtration, washed with water, solids suspended in a solvent composed of a mixture of chloroform and ethyl acetate, the insoluble solid is collected by filtration and the solids washed with chloroform, getting mentioned in the title compound in the form of grey crystals. The output is equal to 0.45 g (41,2%).

Tpl.=175,9-177,2°

1H NMR (DMSO-d6that δ): of 0.95 (3H, t, J=7.4 Hz), of 1.34 (2H, t, J=7,3 Hz), 1,75 (2 is, m), 2,87 (2H, t, J=7,7 Hz), 3,19 (2H, q, J=7,3 Hz), 7,41 (1H, d, J=9.3 Hz), 7,56 (2H, s)to 8.12 (1H, d, J=9,3 Hz).

IR (nujol, cm-1): 3309, 3188, 3059, 1466, 1430, 1348, 1325, 1165, 599.

Reference example 24

Synthesis of 2-ethylsulfanyl-6-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

2 Ethylthio-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl (0,30 g, 1.00 mmol) is suspended in a mixture of acetonitrile (1.0 ml) and water (4.0 ml), to the resulting mixture at 45°With add percarbonate sodium (effective oxygen concentration of 12.2%; 0.33 g, of 2.50 mmol) and stirred at 50-60°C for 2.5 hours. The reaction mixture was poured into water, acidified with diluted hydrochloric acid and the precipitated insoluble solid is collected by filtration and washed with water, getting mentioned in the title compound as white crystals. The output is 0.25 g (75,3%).

Tpl.=232,3-233,0°

1H NMR (DMSO-d6that δ): 0,97 (3H, t, J=7,3 Hz)to 1.21 (3H, t, J=7,3 Hz), of 1.78 (2H, m), 2,96 (2H, t, J=7,7 Hz), 3,62 (2H, q, J=7,3 Hz), a 7.62 (1H, d, J=9.4 Hz), of 7.96 (1H, s)of 8.37 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3354, 3269, 1464, 1351, 1318, 1166, 1137, 743, 711, 452.

Reference example 25

Synthesis of ethyl 6-n-propylimidazol[1,2-b]pyridazin-2-icarbonell

Ethyl 6-chloroimidazo[1,2-b]pyridazin-2-ylcarbonyl (1,00 g, 4,43 mmol) and dichloride, [1,3-bis(diphenylphosphino)propane]Nickel (II) (0.24 g, 0.44 mmol) is added is to tetrahydrofuran (8.0 ml) under nitrogen atmosphere and to this solution with stirring and cooling in an ice bath is added dropwise a solution of n-propylzinc bromide in tetrahydrofuran (0.5m, 13.3 ml of 6.65 mmol). The mixture is stirred for 20 minutes under cooling in an ice bath and for 0.5 hour at room temperature, to the reaction mixture was added with cold water (50,0 ml) and then acidified with diluted hydrochloric acid. The reaction solution is extracted with ethyl acetate, the extracts combined, washed with diluted hydrochloric acid and saturated salt solution. The resulting organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated. The concentrated residue is purified column chromatography on silica gel (acetone:hexane = 1:3), getting mentioned in the title compound as white crystals. The output is of 0.77 g (74.8 percent).

Tpl.=54,0-54,5°

1H NMR (CDCl3that δ): 1,02 (3H, t, J=7.4 Hz), the 1.44 (3H, t, J=7,1 Hz), of 1.80 (2H, m), of 2.81 (2H, t, J=7,6 Hz), 4,47 (2H, q, J=7,1 Hz), 7,00 (1H, d, J=9.5 Hz), of 7.90 (1H, d, J=9.5 Hz), 8,43 (1H, s).

IR (nujol, cm-1): 3121, 1716, 1541, 1306, 1238, 1228, 1195.

Reference example 26

Synthesis of 6-n-propylimidazol[1,2-b]pyridazin-2-ylcarboxamine

Ethyl 6-n-propylimidazol[1,2-b]pyridazin-2-ylcarbonyl (4,90 g, 21,0 mmol) was diluted with acetonitrile (7.0 ml), to this solution was added 28% aqueous ammonia solution (10.0 ml) and stirred at 100°C for 7 hours in a sealed tube. The reaction mixture is cooled to room temperature, diluted with water (0,0 ml), the insoluble solid is collected by filtration and washed with water, getting mentioned in the title compound as white crystals. The output is 3,39 g (79,0%).

Tpl.=223,5-224,2°

1H NMR (CDCl3that δ): 1,02 (3H, t, J=7.4 Hz), to 1.79 (2H, m), of 2.81 (2H, t, J=7,6 Hz), 5,64 (1H, user. C)7,01 (1H, d, J=9.4 Hz), 7,21 (1H, user. C), 7,81 (1H, d, J=9.4 Hz), 8,43 (1H, s).

IR (nujol, cm-1): 3437, 3175, 3104, 1632, 1542, 1319, 1294, 812, 682.

Reference example 27

Synthesis of 6-n-propylimidazol[1,2-b]pyridazin-2-ylcarbonyl

6-n-Propylimidazol[1,2-b]pyridazin-2-ylcarbonyl (3,38 g, 16.5 mmol) dissolved in pyridine (10.0 ml), to this solution under stirring and cooling in an ice bath, add triperoxonane anhydride (3,51 ml of 24.8 mmol), the mixture is stirred for 0.5 hour under cooling in an ice bath and for 0.5 hour at room temperature. The reaction mixture is acidified by adding water and concentrated hydrochloric acid, the insoluble solid is separated by filtration on solid and aqueous solution. The solid is suspended in ether, stirred and insoluble matter is removed by this receiving ether extract. An aqueous solution saturated with sodium chloride and then extracted with ethyl acetate, obtaining an ethyl acetate extract. The ether extract and an ethyl acetate extract of the conc is t and purified column chromatography on silica gel (ethyl acetate:chloroform = 2:5), getting listed in the title compound as white crystals. The output is equal to 2.41 g (78.2%).

Tpl.=81,8-82,4°

1H NMR (CDCl3that δ): 1,02 (3H, t, J=7.4 Hz), of 1.80 (2H, m), and 2.83 (2H, t, J=7,6 Hz), was 7.08 (1H, d, J=9.4 Hz), 7,88 (1H, d, J=9.4 Hz), 8,30 (1H, s).

IR (nujol, cm-1): 3108, 2235, 1544, 1466, 1326, 1292, 1132, 984, 818.

Reference example 28

Synthesis of 2-cyano-6-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

The solution sitedisability in a mixture of heptane-tetrahydrofuran-ethylbenzene (2.0m, up 3.22 ml, 6,44 mmol) diluted with ether (30,0 ml), thereto for 12 minutes at a temperature of -60°or lower added dropwise a solution of 6-n-propylimidazol[1,2-b]pyridazin-2-ylcarbonyl (1,00 g, 5.37 mmol) in ether (20,0 ml) and the mixture was stirred at -60°C for 1.5 hours. Unreacted starting material is not dissolved, so added tetrahydrofuran (20,0 ml) and stirred at -60°C for 1.5 hours. In this mixture at a temperature of -60°or lower for 0.5 hours injected gaseous sulphur dioxide resulting from the interaction of hydrosulfite sodium and concentrated sulfuric acid, and stirred at the temperature of -60°With or below within 20 minutes, after which the temperature of the mixture gradually increased to 0°C. the Precipitated solid is collected by filtration and washed with ether. the received resulting solid is added to a solution of N-chlorosuccinimide (1,15 g, 8,59 mmol) in a mixture of dichloromethane (20,0 ml) and water (20,0 ml) and stirred for 1 hour while cooling in an ice bath. The organic layer is separated and the aqueous layer was extracted with chloroform. The organic layers are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated. The concentrated residue was diluted with acetonitrile (10.0 ml) and added 28% aqueous ammonia solution (2.0 ml)while cooling in an ice bath and stirring at the same temperature for 0.5 hours. The reaction mixture was concentrated, then water is added, the insoluble solid is collected by filtration and washed with water. The resulting solid is washed with chloroform, getting mentioned in the title compound as white crystals. The output is equal to 0.20 g (14,0%).

Tpl.=237,4-243,8°

1H NMR (DMSO-d6that δ): 0,97 (3H, t, J=7,3 Hz), of 1.78 (2H, m), 2,82 (2H, t, J=7,7 Hz), to 7.64 (1H, d, J=9.6 Hz), to 8.20 (2H, user. C), with 8.33 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3316, 3185, 2243, 1550, 1464, 1361, 1175, 606.

Reference example 29

Synthesis of 3-chloro-6-isopropylpyridine

(a) 5-Methyl-4-oxohexanoyl acid (3,60 g 25,0 mmol) and anhydrous hydrazine (0,80 g, 26.0 mmol) is heated for 3 hours in ethanol (36,0 ml) under stirring. After concentrating the reaction solution under reduced pressure to the residue add g is Xan, precipitating crystals, and the crystals are collected by filtration, obtaining 4,5-dihydro-6-isopropyl-3(2H)-pyridazinone in the form of crystals. The output is 3,10,

(b) 4,5-Dihydro-6-isopropyl-3(2H)-pyridazinone (3,10 g) dissolved in acetic acid (30,0 ml) and to this solution for 10 minutes while heating at 100°and With stirring, added dropwise bromine (3.50 g, 22,0 mmol). After boiling the reaction solution under reflux for 1 hour under reduced pressure, distilled acetic acid, to the residue water is added (100 ml) and the mixture is then extracted 5 times with ethyl acetate. Combine the extracts, dried over anhydrous magnesium sulfate and concentrated, obtaining the crude 6-isopropyl-3(2H)-pyridazinone. The output is 3,30,

(c) 6-Isopropyl-3(2H)-pyridazinone (3,30 g) and phosphorus oxychloride (15.0 ml) is refluxed for 1 hour. After distillation of the excess of phosphorus oxychloride to the residue add ice water (200 ml) and then the pH is brought to 6 with 20% aqueous solution of sodium hydroxide. The reaction solution is extracted 3 times with ethyl acetate, the extracts combined, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (ethyl acetate:chloroform = 1:2), getting mentioned in the title compound as pale red crystals. The output is equal to 1.60 g (40.8 percent 5-methyl-4-oxohexanoate is islote).

Tpl.=32-33°

1H NMR (CDCl3that δ): 1,35-1,40 (6N, m)to 3.33 (1H, Sept, J=7.0 Hz), 7,34 (1H, d, J=8,8 Hz), 7,44 (1H, d, J=8,8 Hz).

IR (nujol, cm-1): 1572, 1540, 1409, 1167, 1149, 1069, 1041, 854, 790.

Reference example 30

Synthesis of 3-amino-6-isopropylpyridine

3-Chloro-6-isopropylpyridine (1.60 g, 10.2 mmol) and 28% aqueous ammonia solution (15.0 ml) are placed in a reactor in the form of a sealed tube and stirred under pressure at 140°within 24 hours and at 165°C for 25 hours. The reaction solution is allowed to cool, poured into water (30,0 ml), adjusted pH to 9, and extracted 3 times with ethyl acetate. Combine the extracts, dried over anhydrous sodium sulfate and concentrated under reduced pressure, obtaining crude crystals. The crystals are filtered off, washing with a mixture of diisopropyl ether/hexane, getting mentioned in the title compound as light brown crystals. The output is the 0,41 g (29,3%).

Tpl.=131-132°

1H NMR (CDCl3that δ): 1,30 (6N, d, J=7,0 Hz), 3,17 (1H, Sept, J=7.0 Hz), 4,69 (2H, user. C)6,72 (1H, d, J=9.1 Hz), 7,12 (1H, d, J=9.1 Hz).

IR (nujol, cm-1): 3312, 3139, 1645, 1608, 1555, 1056, 850, 840, 651.

Reference example 31

Synthesis of 6-isopropyl-2-methylimidazo[1,2-b]pyridazine

3-Amino-6-isopropylpyridine (0,41 g, 2,99 mmol) and bromoacetone (0,53 g, 3.10 mmol) is mixed with acetone what Rila (5.0 ml) and refluxed for 6 hours. After completion of the reaction solution is poured in water (20,0 ml) and the pH adjusted to 9 with 20% aqueous solution of sodium hydroxide. The reaction solution is extracted twice with ethyl acetate and the extracts are combined, dried over anhydrous sodium sulfate and concentrated. The residue is purified column chromatography on silica gel (ethyl acetate:chloroform = 1:1), obtaining mentioned in the title compound as a brown oily substance. Yield 0.30 g (57,2%).

1H NMR (CDCl3that δ): 1,33 (6N, d, J=7,0 Hz), 2,48 (3H, d, J=0.8 Hz), to 3.09 (1H, Sept, J=7.0 Hz), make 6.90 (1H, d, J=9.4 Hz), 7,65-to 7.67 (1H, m), 7,74 (1H, d, J=9.4 Hz).

IR (pure, cm-1): 1539, 1327, 1289, 1123, 1084, 1042, 989, 815, 727.

Reference example 32

Synthesis of 6-isopropyl-2-methylimidazo[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as light brown crystals by the same reaction as in reference example 4, except that instead of 2-chloro-6-n-propylimidazol[1,2-b]pyridazine use 6-isopropyl-2-methylimidazo[1,2-b]pyridazin. The output is 27.6 per cent.

Tpl.=199-200°

1H NMR (DMSO-d6that δ): 1,32 (6N, d, J=6.9 Hz), to 2.57 (3H, s), a 3.2 and 3.4 (1H, m), 7,44 (2H, user. C), 7,47 (1H, d, J=9.5 Hz), 8,11 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3338, 3067, 1543, 1347, 1332, 1162, 1047, 828, 763, 740, 606.

Reference example 33

Synthesis of 6-chloro-2-n-propylimidazol[1,2-b]pyridazine

p>

The crude product get the same reaction as in reference example 31, except that instead of 3-amino-6-isopropylpyridine using 3-amino-6-chloropyridazine and 1-chloro-2-pentanon used instead of bromoacetone. This product was then purified column chromatography on silica gel (ethyl acetate:chloroform = 1:2), receiving specified in the title compound in the form of flesh-colored crystals. The output is 43.7 per cent.

1H NMR (CDCl3that δ): 1,00 (3H, t, J=7.4 Hz), 1,7-1,9 (2H, m), and 2.79 (2H, t, J=7,6 Hz), of 6.99 (1H, d, J=9.4 Hz), 7,71 (1H, s), 7,80 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 1608, 1518, 1455, 1328, 1286, 1133, 1091, 987, 940, 818, 764, 708, 603, 508.

Reference example 34

Synthesis of 6-chloro-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as white crystals in the same manner as in reference example 6, except that instead of 2-chloro-6-n-butylimido[1,2-b]pyridazine using 6-chloro-2-n-propylimidazol[1,2-b]pyridazin. The output is 45,1%.

Tpl.=155-156°C (decomp.)

1H NMR (DMSO-d6that δ): 0,94 (3H, t, J=7,3 Hz), 1,7-1,8 (2H, m), 2,98 (2H, t, J=7.4 Hz), to 7.59 (1H, d, J=9.5 Hz), of 7.75 (2H, user. C)8,30 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3404, 3259, 1524, 1359, 1298, 1180, 1164, 1142, 818, 737, 612.

Reference example 35

Synthesis of 2-chloro-6-isopropylimidazole[1,2-b]pyridazine

Mix Chloroacetic acid (0.32 g, 3.3 mmol), triethylamine (0.33 g, 3.3 mmol), ethanol (5.0 ml) and water (5.0 ml) and to this mixture, with stirring, at room temperature, add 3-amino-6-isopropylpyridine (0.45 g, or 3.28 mmol) and, after heating the mixture at a temperature of from 80 to 90°C for 5 hours under stirring, the reaction solution is concentrated until dry. The resulting solid substance and phosphorus oxychloride (5.0 ml) was stirred at 150°C for 12 hours in the reactor in the form of a closed tube. The reaction solution is allowed to cool to room temperature and poured into water (50,0 ml) with temperatures ranging from 40 to 50°to destroy the excess of phosphorus oxychloride. Adjust the pH of the reaction solution to 7 20% aqueous sodium hydroxide solution and extracted three times with ethyl acetate, the extracts combined, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (ethyl acetate:chloroform = 1:2), getting mentioned in the title compound as pale yellow crystals. Yield 0.15 g (23,4%).

Tpl.=69-71°

1H NMR (CDCl3that δ): 1,34 (6N, d, J=7,0 Hz), the 3.11 (1H, Sept, J=7.0 Hz), of 6.99 (1H, d, J=9.4 Hz), 7,75-7,8 (2H, m).

IR (nujol, cm-1): 3128, 3050, 1545, 1347, 1327, 1306, 1275, 1257, 1192, 1140, 1088, 1044, 961.

Reference example 36

Synthesis of 2-chloro-6-isopropylimidazole[1,2-b]is ridazin-3-ralfinamide

Specified in the title compound obtained as light brown crystals by the same reaction as in reference example 4, except that instead of 2-chloro-6-n-propylimidazol[1,2-b]pyridazine use of 2-chloro-6-isopropylimidazole[1,2-b]pyridazin. The output is 28.5%.

Tpl.=179-180°C (decomp.)

1H NMR (DMSO-d6that δ): 1,33 (6N, d, J=6.9 Hz), or 3.28 (1H, Sept, J=6.9 Hz), to 7.61 (1H, d, J=9.5 Hz), to 7.77 (2H, user. C), 8,21 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3347, 1549, 1460, 1379, 1366, 1357, 1331, 1317, 1254, 1174, 1166, 1069, 1036, 903, 826.

Reference example 37

Synthesis of 2-chloro-6-ethylimidazole[1,2-b]pyridazine

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 3, except that instead of the solution of propylaniline in tetrahydrofuran use a solution of ethylmagnesium in tetrahydrofuran. The output is 66,2%.

1H NMR (CDCl3that δ): up to 1.35 (3H, t, J=7,6 Hz), 2,85 (2H, q, J=7,6 Hz), 6,97 (1H, d, J=9.3 Hz), of 7.75 (1H, d, J=9.3 Hz), 7,80 (1H, s).

IR (nujol, cm-1): 3121, 3058, 1544, 1471, 1318, 1280, 1262, 1189, 1142, 1121, 1059, 983, 953, 822.

Reference example 38

Synthesis of 2-chloro-6-ethylimidazole[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as light brown crystals takoyzhe reaction as in reference example 4, except that instead of 2-chloro-6-n-propylimidazol[1,2-b]pyridazine use of 2-chloro-6-ethylimidazole[1,2-b]pyridazin. The output is 74,1%.

Tpl.=204-205°

1H NMR (DMSO-d6that δ): 1,31 (3H, t, J=7,6 Hz), 2,95 (2H, q, J=7,6 Hz), 7,54 (1H, d, J=9.4 Hz), 7,82 (2H, user. C), 8,19 (1H, d, J=9.4 Hz).

IR (nujol, cm-1): 3317, 3211, 1365, 1356, 1325, 1172, 829, 668.

Reference example 39

Synthesis of 2-methyl-6-n-propylimidazol[1,2-b]pyridazine

Specified in the title compound obtained as a reddish oily substance the same reaction as in reference example 1, except that instead of the solution ethylacetamide in the air use a solution of n-propylaniline in ether and the solvent instead of a mixture of ether and tetrahydrofuran (THF) using tetrahydrofuran. The output is 19,1%.

1H NMR (CDCl3that δ): 1,00 (3H, t, J=7.4 Hz), 1,7-1,9 (2H, m), 2,48 (3H, d, J=0.7 Hz), 2,77 (2H, t, J=7.5 Hz), 6,85 (1H, d, J=9,2 Hz), 7,66 (1H, d, J=0.7 Hz), 7,72 (1H, d, J=9,2 Hz).

IR (nujol, cm-1): 2961, 1541, 1464, 1326, 1296, 1153, 1124, 989, 816, 726.

Reference example 40

Synthesis of 2-methyl-6-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as light brown crystals by the same reaction as in reference example 4, except that instead of 2-chloro-6-n-propylene the azo[1,2-b]pyridazine using 2-methyl-6-n-propylimidazol[1,2-b]pyridazin. The yield was 14.6%.

Tpl.=178-179°C (decomp.)

1H NMR (DMSO-d6that δ)as 0.96 (3H, t, J=7,3 Hz), 1,7-1,9 (2H, m), of 2.56 (3H, s), 2,8-2,9 (2H, m), 7,39 (1H, d, J=9.3 Hz), 7,46 (2H, user. C)8,08 (1H, d, J=9,3 Hz).

IR (nujol, cm-1): 3384, 3327, 1543, 1508, 1420, 1348, 1327, 1309, 1162, 827.

Reference example 41

Synthesis of 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as white crystals by the same reaction as in reference example 6, except that instead of 2-chloro-6-n-butylimido[1,2-b]pyridazine using 6-chloro-2-ethylimidazole[1,2-b]pyridazin. The output is 11.5%.

Tpl.=201-203°

1H NMR (DMSO-d6that δ): of 1.27 (3H, t, J=7.5 Hz), 3,01 (2H, q, J=7.5 Hz), to 7.59 (1H, d, J=9.5 Hz), 7,74 (2H, s), 8,30 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3347, 1520, 1503, 1462, 1448, 1346, 1298, 1171, 1134, 1076, 819, 737.

Reference example 42

Synthesis of 2-ethyl-6-atitikimas[1,2-b]pyridazin-3-ralfinamide

In DMF (5.0 ml) suspended for 60% sodium hydride (0,19 g of 4.75 mmol) and to this mixture with stirring, add ethanthiol (0,29 g, 4.6 mmol). After cessation of hydrogen evolution to this mixture is added 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ylsulphonyl (0,30 g, 1.15 mmol) and stirred at 50°C for 3 hours. After completion of the reaction, the reaction solution was poured into water (50,0 ml, the pH was adjusted to 2 with diluted hydrochloric acid, the precipitated crystals are filtered and washed with water and ether, getting mentioned in the title compound as pale yellow crystals. The output is equal to 0.19 g (57,3%).

Tpl.=164-165°

1H NMR (DMSO-d6that δ): of 1.26 (3H, t, J=7.5 Hz), of 1.37 (3H, t, J=7,3 Hz), 2,98 (2H, q, J=7.5 Hz), and 3.31 (2H, q, J=7,3 Hz), 7,31 (1H, d, J=9.5 Hz), 7,39 (2H, s), 8,01 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3384, 1353, 1336, 1301, 1163.

Reference example 43

Synthesis of 6-methylthio-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 42, except that instead of 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl and methanethiol used instead of ethanthiol. The output is 73,3%.

Tpl.=185-187°

1H NMR (DMSO-d6that δ): 0,93 (3H, t, J=7.4 Hz), 1,6-1,8 (2H, m)to 2.67 (3H, s)to 2.94 (2H, t, J=7.4 Hz), was 7.36 (1H, d, J=9.5 Hz), 7,39 (2H, user. C)8,01 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3378, 1536, 1446, 1307, 1171, 823, 616.

Reference example 44

Synthesis of 6-ethoxy-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-yellow crystals by the same Rea is a function as in reference example 42, except that instead of 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl and ethanol is used instead of ethanthiol. The output is to 77.7%.

Tpl.=170-176°

1H NMR (DMSO-d6that δ): 0,93 (3H, t, J=7.4 Hz), of 1.39 (3H, t, J=7.0 Hz), 1,6-1,8 (2H, m), only 2.91 (2H, t, J=7.4 Hz), 4,48 (2H, q, J=7.0 Hz), 7,06 (1H, d, J=9.7 Hz), 7,40 (2H, user. C)of 8.06 (1H, d, J=9.7 Hz).

IR (nujol, cm-1): 3351, 1551, 1504, 1346, 1166, 823, 629.

Reference example 45

Synthesis of 6-dimethylamino-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide

A mixture of 6-chloro-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide (0.50 g, is 1.81 mmol), 50% aqueous dimethylamine (1.0 ml) and tert-butanol (5.0 ml) is heated at 100°C for 8 hours under stirring in a reactor in the form of a closed tube. The reaction solution is allowed to cool to room temperature, poured it in the water (50,0 ml) and adjusted pH to 6 with diluted hydrochloric acid, precipitating the crystals are then filtered off and washed with water, getting mentioned in the title compound as light yellow crystals. The output is equal to 0.38 g (74,0%).

Tpl.=215-217°

1H NMR (DMSO-d6that δ): to 0.92 (3H, t, J=7,3 Hz), 1,6-1,8 (2H, m), 2,87 (2H, t, J=7.4 Hz), 3.00 and (6N, (C), 7,13 (2H, user. C), 7,20 (1H, d, J=10.0 Hz), 7,86 (1H, d, J=10.0 Hz).

IR (nujol, cm-1): 3340, 1565, 1501, 1345, 1318, 1163, 810, 623.

Reference example 46

Synthesis of 6-chloro-2-triptoreline[1,2-b]pyridazin-3-ralfinamide

6-Chloro-2-triptoreline[1,2-b]pyridazin (6,00 g, 27,1 mmol) was dissolved in 1,1,2,2-tetrachlorethane (60,0 ml) and to this solution was added with stirring chlorosulfonic acid (97%, 2,80 ml of 40.7 mmol) at room temperature. The mixture is refluxed for 8 hours, then cooled to room temperature and dropwise added triethylamine (4,39 g, a 43.4 mmol) and phosphorus oxychloride (7.47 g, 48.7 per mmol). The reaction mixture is heated at 120°C for 3 hours under stirring, then cooled to 50°and to it was added water (150 ml). After distribution of the reaction solution, the aqueous layer was twice extracted with chloroform, the organic layers combined washed twice with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is dissolved in acetonitrile (100 ml) and stirred at room temperature, during which the solution was added aqueous ammonia (14 M 9,00 ml, 126 mmol). The reaction solution was stirred at room temperature for 2 hours, poured into a mixture of ice water (400 ml) and the pH adjusted to 2 with concentrated hydrochloric acid, precipitating the crystals are then filtered off and washed with water. Crystals sushi is t and then purified by chromatography on silica gel (ethyl acetate:chloroform = 1:9→ 1:4→1:2), getting mentioned in the title compound as colorless crystals. The output is equal to 3.80 g (46,6%).

Tpl.=223,0-223,5°

1H NMR (DMSO-d6that δ): to 7.77 (1H, d, J=9.6 Hz), to 8.20 (2H, user. C)charged 8.52 (1H, d, J=9.6 Hz).

19F NMR (DMSO-d6that δ): -58,48

IR (nujol, cm-1): 3177, 3104, 3089, 3069, 1568, 1530, 1452, 1385, 1371, 1361, 1307, 1243, 1173, 1157, 1133, 1119, 1041, 928, 840.

Reference example 47

Synthesis of 6-ethylthio-2-triptoreline[1,2-b]pyridazin-3-ralfinamide

6-chloro-2-triptoreline[1,2-b]pyridazin-3-ylsulphonyl (1,00 g of 3.33 mmol) suspended in tert-butyl alcohol (20,0 ml) and stirred at room temperature, during which they added tert-piperonyl potassium (80%, 1.40 g, 9,98 mmol) and ethanthiol (0.54 ml, 7,29 mmol). After boiling the mixture under reflux for 4 hours, the reaction solution is allowed to cool to room temperature, poured into a mixture of ice water (200 ml) and the pH adjusted to 3. The precipitated crystals are filtered and washed with water, getting mentioned in the title compound as colorless crystals. The output is of 0.54 g (50,0%).

Tpl.=208-210°

1H NMR (DMSO-d6that δ): to 1.38 (3H, t, J=7,3 Hz), the 3.35 (2H, q, J=7,3 Hz), of 7.48 (1H, d, J=9.6 Hz), 7,83 (2H, user. C), 8,18 (1H, d, J=9.6 Hz).

19F NMR (DMSO-d6that δ): -58,22

IR (nujol, cm-1): 3368, 3198, 3100, 3061, 1598, 1540, 1532, 1455, 1375,1360, 1320, 1210, 1182, 1162, 1130, 1112, 1038, 973, 916, 820.

Reference example 48

Synthesis of 6-ethoxy-2-triptoreline[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 42, except that instead of 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-triptoreline[1,2-b]pyridazin-3-ylsulphonyl and ethanol is used instead of ethanthiol. The output amounted to 83.1%.

Tpl.=191-192°

1H NMR (DMSO-d6that δ): of 1.41 (3H, t, J=7.0 Hz), 4,55 (2H, q, J=7.0 Hz), 7,25 (1H, d, J=9.8 Hz), 7,88 (2H, user. C), compared to 8.26 (1H, d, J=9.8 Hz).

19F NMR (DMSO-d6that δ): -58,17

IR (nujol, cm-1): 3370, 3266, 1618, 1558, 1522, 1493, 1473, 1388, 1371, 1324, 1315, 1296, 1234, 1203, 1180, 1165, 1147, 1122, 1041, 1024, 1003, 906, 828, 732.

Reference example 49

Synthesis of 6-methylthio-2-triptoreline[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as colorless crystals by the same reaction as in reference example 47, except that instead of a combination of tert-butoxide potassium and ethanthiol use an aqueous solution of sodium salt of methanethiol. The output is of 87.5%.

Tpl.=272-273°

1H NMR (DMSO-d6that δ): 2,71 (3H, s), 7,53 (1H, d, J=9.6 Hz), to 7.84 (2H, user. C), 8,18 (1H, d, J=9,GC).

19F NMR (DMSO-d6that δ): -58,25

IR (nujol, cm-1): 3356, 3260, 3095, 3029, 1557, 1538, 1523, 1449, 1372, 1360, 1307, 1206, 1182, 1168, 1144, 1115, 1037, 929, 823.

Reference example 50

Synthesis of 2-ethyl-6-methylimidazo[1,2-b]pyridazine

3-Amino-6-methylpyridazine (4,00 g, 27.5 mmol) and 1-bromo-2-butanone (90%, 7,38 g, to 44.0 mmol) is refluxed in 1-propanol (40,0 ml) for 13 hours. The reaction solution is cooled to room temperature and concentrated under reduced pressure, then the residue is dissolved in acetone (50,0 ml) and neutralized with 20% aqueous solution of sodium hydroxide. The reaction solution is concentrated under reduced pressure and then the residue is dissolved in chloroform, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (isopropanol:hexane = 1:2), receiving specified in the title compound in the form of grey crystals. The output is of 2.33 g (39.4 percent).

Tpl.=53-55°

1H NMR (CDCl3that δ): up to 1.35 (3H, t, J=7.5 Hz), 2,53 (3H, s)2,84 (2H, q, J=7.5 Hz), at 6.84 (1H, d, J=9,2 Hz), the 7.65 (1H, s), 7,72 (1H, d, J=9,2 Hz).

Reference example 51

Synthesis of 2-ethyl-6-methylimidazo[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as light brown crystals by the same reaction as in reference example 2, except for the m, instead of 6-ethyl-2-methylimidazo[1,2-b]pyridazine use 2-ethyl-6-methylimidazo[1,2-b]pyridazin. The output is to 44.0%.

Tpl.=198-199°

1H NMR (DMSO-d6that δ): a 1.25 (3H, t, J=7.5 Hz), 2,62 (3H, s)to 2.99 (2H, q, J=7.5 Hz), 7,34 (1H, d, J=9.3 Hz), 7,49 (2H, user. C)8,08 (1H, d, J=9,3 Hz).

IR (nujol, cm-1): 3312, 3195, 3061, 1578, 1546, 1489, 1397, 1383, 1363, 1342, 1306, 1202, 1169, 1133, 1083, 1036, 990, 906, 853, 818.

Reference example 52

Synthesis of 2-ethyl-6-dimethylaminopyridine[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as colorless crystals by the same reaction as in reference example 45, except that instead of 6-chloro-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ylsulphonyl. The output is 87,4%.

Tpl.=211-213°

1H NMR (DMSO-d6that δ): 1,22 (3H, t, J=7.5 Hz), only 2.91 (2H, q, J=7.5 Hz), 3,10 (6N, (C), 7,14 (2H, user. C)7,19 (1H, d, J=10.0 Hz), the 7.85 (1H, d, J=10.0 Hz).

IR (nujol, cm-1): 3318, 2695, 1629, 1604, 1556, 1504, 1462, 1429, 1406, 1375, 1363, 1349, 1334, 1323, 1312, 1276, 1221, 1183, 1163, 1148, 1100, 1061, 1049, 970.

Reference example 53

Synthesis of 2-ethyl-6-methylthioribose[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as colorless crystals by the same reaction as in reference example 47, except that pax is 6-chloro-2-triptoreline[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ylsulphonyl and instead of a combination of tert-butoxide potassium and ethanthiol use an aqueous solution of sodium salt of methanethiol. The output is to 78.3%.

Tpl.=196-197°

1H NMR (DMSO-d6that δ): of 1.26 (3H, t, J=7.5 Hz), to 2.67 (2H, s), 2,98 (2H, q, J=7.5 Hz), was 7.36 (1H, d, J=9.5 Hz), 7,40 (2H, user. C)of 8.00 (1H, d, J=9.5 Hz).

Reference example 54

Synthesis of 2-ethyl-6-methylsulfonylmethane[1,2-b]pyridazin-3-ralfinamide

2-Ethyl-6-methylthioribose[1,2-b]pyridazin-3-ylsulphonyl (1.10 g, 4.04 mmol) was dissolved in DMF (10.0 ml) and stirred under cooling in an ice bath, during which to this solution was added m-chloroperbenzoic acid (abbreviated as m-HPBC) (70%, 2,48 g, 10.1 mmol). The mixture is stirred under cooling in an ice bath for 1 hour and at room temperature for 3 hours, then the reaction solution was poured into water (50,0 ml) and to this mixture is added 25% aqueous ammonia (1.0 ml). After stirring the reaction solution for 5 minutes, the precipitated crystals are filtered and washed with water, getting mentioned in the title compound as colorless crystals. The output is equal to 1.04 g (84,5%).

Tpl.=225-226°

1H NMR (DMSO-d6that δ): of 1.29 (3H, t, J=7.5 Hz), to 3.09 (2H, q, J=7.5 Hz), 3,63 (3H, s), 7,89 (2H, user. C)7,94 (1H, d, J=9.5 Hz), 8,53 (1H, d, J=9.5 Hz).

IR (nujol, cm-1): 3615, 3352, 3015, 1608, 1547, 1523, 1505, 1455, 1411, 1396, 1369, 1339, 1313, 1266, 1210, 1171, 1158, 1130, 1117, 1082, 1000, 969, 919, 826.

Reference example 55

Synthesis of 2-ethyl-6-methoxyimino[1,2-b]pyrido the Jn-3-ralfinamide

6-Chloro-2-ethylimidazole[1,2-b]pyridazin-3-ylsulphonyl (1.50 g, of 5.75 mmol) suspended in methanol (30,0 ml) and stirred at room temperature, during which this mixture is added sodium methoxide (28%, 3,34 g, 17.3 mmol). The mixture is refluxed for 5 hours, then the reaction solution is poured into a mixture of ice water (200 ml) and the pH adjusted to 2 with concentrated hydrochloric acid. The precipitated crystals are filtered and washed with water, getting mentioned in the title compound as colorless crystals. The output is 1.02 g (69.3 percent).

Tpl.=213-214°

1H NMR (DMSO-d6that δ): 1,24 (3H, t, J=7.5 Hz), 2,96 (2H, q, J=7.5 Hz), of 4.05 (3H, s), was 7.08 (1H, d, J=9.6 Hz), 7,42 (2H, user. C)of 8.06 (1H, d, J=9.6 Hz).

Reference example 56

Synthesis of 2-ethyl-6-toxemias[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-orange crystals by the same reaction as in reference example 55, except that instead of a combination of sodium methoxide and methanol use a combination of ethoxide sodium and ethanol. The output is 68,0%.

Tpl.=200-202°

1H NMR (DMSO-d6that δ): a 1.25 (3H, t, J=7.5 Hz), of 1.39 (3H, t, J=7,1 Hz), 2,96 (2H, q, J=7.5 Hz), of 4.49 (2H, q, J=7,1 Hz), 7,05 (1H, d, J=9.7 Hz), 7,40 (2H, user. C)of 8.06 (1H, d, J=9.7 Hz).

IR (nujol, see -1): 3320, 1340, 1280, 1210, 1165, 825.

Reference example 57

Synthesis of 6-ethoxy-2-methylimidazo[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as white crystals by the same reaction as in reference example 55, except that instead of 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-methylimidazo[1,2-b]pyridazin-3-ylsulphonyl and instead of the combination of sodium methoxide and methanol use a combination of ethoxide sodium and ethanol. The output is 92,0%.

Tpl.=225-226°

1H NMR (DMSO-d6that δ): of 1.39 (3H, t, J=7.5 Hz), to 2.55 (3H, s), 4,50 (2H, q, J=7.5 Hz), 7,03 (1H, d, J=9.6 Hz), 7,38 (2H, user. C)8,02 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3355, 1349, 1293, 1222, 1172, 826.

Reference example 58

Synthesis of 6-ethylthio-2-methylimidazo[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as light brown crystals by the same reaction as in reference example 47, except that instead of 6-chloro-2-triptoreline[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2-methylimidazo[1,2-b]pyridazin-3-ylsulphonyl. The output is 62,0%.

Tpl.=217-219°

1H NMR (DMSO-d6that δ): of 1.36 (3H, t, J=7.2 Hz), of 2.56 (3H, s), 3,30 (2H, q, J=7.2 Hz), 7,29 (1H, d, J=9.3 Hz), 7,38 (2H, user. C)of 7.97 (1H, d, J=9,3 Hz).

-1): 3380, 1343, 1303, 1169, 1141, 1068, 816.

Reference example 59

Synthesis of 2-methyl-6-methylsulfonylmethane[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 54, except that instead of 2-ethyl-6-methylthioribose[1,2-b]pyridazin-3-ralfinamide using 2-methyl-6-methylthioribose[1,2-b]pyridazin-3-ylsulphonyl. The output is of 84.0%.

Tpl.=245-246°

1H NMR (DMSO-d6that δ): 2,69 (3H, s), 3,63 (3H, s), 7,88 (2H, user. C)7,88 (1H, d, J=9.6 Hz), and 8.50 (1H, d, J=9.6 Hz).

IR (nujol, cm-1): 3380, 1348, 1323, 1174, 1122, 778, 723.

Reference example 60

Synthesis of 2-chloro-6-isopropoxypyridine[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as white crystals by the same reaction as in reference example 55, except that instead of 6-chloro-2-ethylimidazole[1,2-b]pyridazin-3-ralfinamide using 2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl and instead of the combination of sodium methoxide and methanol use a combination of isopropoxide sodium and isopropanol. The output is to 82.6%.

Tpl.=213-214°

1H NMR (DMSO-d6that δ): 1,40 (6N, d, J=6.0 Hz), of 5.48 (1H, Sept, J=6.0 Hz), 7,10 (1H, d, J=9.6 Hz), 7,74 (2H, s), of 8.09 (1H, d, J=9.6 Hz).

The background is the first example 61

Synthesis of 2-chloro-6-ethylaminoethanol[1,2-b]pyridazin-3-ralfinamide

2,6-Dichloroimidazo[1,2-b]pyridazin-3-ylsulphonyl (2.00 g, 7,50 mmol) and ethylamine (50%, 10.0 ml) was stirred in acetonitrile (100 ml) at 70°C for 8 hours. The reaction mixture is concentrated until dry, dissolved in a mixture of ice water (to 50.0 ml) and the pH adjusted to 6 with concentrated hydrochloric acid. The precipitated crystals are filtered and washed with water, getting mentioned in the title compound as pale yellow crystals. The output is equal to 1.10 g (53,3%).

Tpl.=218-220°

1H NMR (DMSO-d6that δ): 1,22 (3H, t), 3,23-to 3.67 (1H, m), 6.90 to (1H, d), 7,27 (2H, user. C)to 7.67 (1H, d).

Reference example 62

Synthesis of 6-chloro-2,8-dimethylimidazo[1,2-b]pyridazine

3-Amino-6-chloro-4-methylpyridazin (5.50 g, to 38.3 mmol) and bromoacetone (6,90 g, 40.0 mmol) is refluxed in acetonitrile (50,0 ml) for 8 hours. The reaction solution is concentrated under reduced pressure, to the residue water is added (100 ml), then pH adjusted to 9 with 20% aqueous sodium hydroxide and extracted twice with ethyl acetate. The extracts are combined, dried over anhydrous magnesium sulfate, concentrated and the residue purified column chromatography on silica gel (ethyl acetate:chloroform = 1:2), receiving specified in the header soedinenii the form of white crystals. The output is equal to 3.80 g (54,6%).

Tpl.=109-110°

1H NMR (CDCl3that δ): 2,49-of 2.50 (3H, m), 2,63-of 2.64 (3H, m), 6,83-6,85 (1H, m), 7,66 (1H, s).

IR (nujol, cm-1): 3129, 1592, 1532, 1289, 1113, 1092, 985, 928, 843, 772.

Reference example 63

Synthesis of 6-chloro-2,8-dimethylimidazo[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as white crystals by the same reaction as in reference example 2, except that instead of 6-ethyl-2-methylimidazo[1,2-b]pyridazine using 6-chloro-2,8-dimethylimidazo[1,2-b]pyridazin. The output consists of 51.1%.

Tpl.=247-248°

1H NMR (DMSO-d6that δ): 2,59 (6N,) and 7.5 and 7.6 (1H, m), 7,71 (2H, user. C).

IR (nujol, cm-1): 3324, 3160, 3063, 1557, 1509, 1459, 1377, 1340, 1295, 1170, 1134, 1067, 933, 910, 863, 724, 613.

Reference example 64

Synthesis of 2,8-dimethyl-6-dimethylaminopyridine[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 45, except that instead of 6-chloro-2-n-propylimidazol[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2,8-dimethylimidazo[1,2-b]pyridazin-3-ylsulphonyl. The output is 85.9%.

Tpl.=248-249°

1H NMR (DMSO-d6that δ): 2,4-2,5 (6N, m)is 3.08 (6N, (C), was 7.08 (1H, s), 7,12 (2H, user. C).

IR (nujol, cm-1): 3349, 611, 1525, 1352, 1320, 1184, 1166, 1135, 901, 763, 619.

Reference example 65

Synthesis of 2,8-dimethyl-6-methylthioribose[1,2-b]pyridazin-3-ralfinamide

Specified in the title compound obtained as pale-yellow crystals by the same reaction as in reference example 47, except that instead of 6-chloro-2-triptoreline[1,2-b]pyridazin-3-ralfinamide using 6-chloro-2,8-dimethylimidazo[1,2-b]pyridazin-3-ylsulphonyl and instead of the combination of ethanthiol and tert-butoxide potassium using an aqueous solution of sodium salt of methanethiol. The output is 62.2%.

Tpl.=233-234°

1H NMR (DMSO-d6that δ): 2,50 (3H, s)to 2.55 (3H, s)of 2.64 (3H, s), 7.24 to to 7.25 (1H, m), 7,38 (2H, user. C).

IR (nujol, cm-1): 3373, 1346, 1292, 1179, 1138, 1127, 858, 730, 611.

Example of synthesis 1

Synthesis of 1-(4,6-dimethoxypyrimidine-2-yl)-3-(6-ethyl-2-methylimidazo[1,2-b]pyridazin-3-ylsulphonyl)urea (Compound No. 13)

As shown in the above reaction scheme, 6-ethyl-2-methylimidazo[1,2-b]pyridazin-3-ylsulphonyl (0,60 g of 2.50 mmol) and phenyl N-(4,6-dimethoxypyrimidine-2-yl)carbamate (0,76 g, was 2.76 mmol) suspended in acetonitrile (10 ml) and stirred while cooling in an ice bath, to this mixture is added DBU (0,46 g, to 3.02 mmol). The temperature of the reaction solution was raised to room temperature and the mixture was stirred at this te is the temperature for 4 hours. The reaction solution is poured into a mixture of ice water (150 ml) and the pH adjusted to 3 with concentrated hydrochloric acid. The reaction mixture was stirred at room temperature for 5 minutes, the precipitated crystals are washed with water, acetonitrile and diethyl ether in this order and collected by filtration. The crystals are dried under reduced pressure, obtaining mentioned in the title compound as colorless crystals. The output is equal to 0.55 g (52%), melting point 172-174°C.

1H NMR (DMSO-d6that δ ppm): of 1.02 (3H, t, J=7.5 Hz), of 2.64 (3H, s), 2,69 (2H, q, J=7.5 Hz), 3,97 (6N, (C), 6,03 (1H, s), 7,44 (1H, d, J=9.4 Hz), 8,15 (1H, d, J=9.4 Hz), 10,56 (1H, s), 13,21 (1H, user. C).

Example of synthesis 2

Synthesis of 1-(4,6-dimethoxypyrimidine-2-yl)-3-(2-ethyl-6-atitikimas[1,2-b]pyridazin-3-ylsulphonyl)urea (Compound No. 7)

As shown in the above reaction scheme, 2-ethyl-6-atitikimas[1,2-b]pyridazin-3-ylsulphonyl (0,19 g, 0.66 mmol) and phenyl N-(4,6-dimethoxypyrimidine-2-yl)carbamate (0.20 g, 0.73 mmol) suspended in acetonitrile (5 ml) and stirred at room temperature, to this mixture is added DBU (0.11 g, 0.73 mmol). After the mixture was stirred at room temperature for 2 hours, the reaction solution was poured into water (50 ml) and the pH adjusted to 2 with diluted hydrochloric acid. The precipitated crystals are collected is by filtration, washed with water and ether in this order. The crystals are dried under reduced pressure, obtaining mentioned in the title compound as colorless crystals. The output is equal to 0.18 g (58%), the melting point of 160-165°C (decomp.).

1H NMR (DMSO-d6that δ ppm): to 1.21 (3H, t, J=7.5 Hz), is 1.31 (3H, t, J=7.5 Hz), to 3.0-3.2 (4H, m), 3,93 (6N, (C), the 6.06 (1H, s), 7,42 (1H, d, J=9.5 Hz), of 8.09 (1H, d, J=9.6 Hz), 10,59 (1H, user. C)to 12.9 (1H, user. C).

Example of synthesis 3

Synthesis of 1-(4,6-dimethoxypyrimidine-2-yl)-3-(6-ethoxy-2-methylimidazo[1,2-a]pyridine-3-ylsulphonyl)urea (Compound No. 32)

As shown in the above reaction scheme, 6-ethoxy-2-methylimidazo[1,2-a]pyridine-3-ylsulphonyl (0.04 g, 0,156 mmol) and phenyl N-(4,6-dimethoxypyrimidine-2-yl)carbamate (0,048 g, 0,172 mmol) suspended in acetonitrile (1 ml) and stirred at room temperature, to this mixture is added DBU (0,026 g, 0,172 mmol). After the mixture was stirred at room temperature for 2 hours, the reaction solution was poured into water (20 ml) and the pH adjusted to 3 with diluted hydrochloric acid. The precipitated crystals are collected by filtration, washed with water and ether in this order. The crystals are dried under reduced pressure, obtaining mentioned in the title compound as light brown crystals. The output is equal to 0.06 g (87%), melting point 159-164°C (decomp.).

H NMR (DMSO-d6that δ ppm): to 1.38 (3H, t, J=7.0 Hz), of 2.56 (3H, s), 3,92 (6N, (C), of 4.05 (2H, q, J=6.9 Hz), 6,00 (1H, s), 7,3-7,5 (1H, m), the 7.65 (1H, d, J=9.7 Hz), 8,3 an 8.4 (1H, m), 10,54 (1H, user. C)a 12.7-13,0 (1H, user. C).

The compounds shown in the following tables 1-4, and compound No. 35 synthesized in the same manner as described above. As control compounds used in the following test examples were synthesized compounds comparisons 1 and 2. The table also shows the above-described compound No. 13, 7 and 32.

Table 1
Connection # R1R2R3XTpl.(°)
1With2H5NCH3OCH3182-184
2With2H5NClOCH3174-175
3ClNNHC2H5OCH3169-171
4With2H5NN(CH3)2OCH3174-176
5With H5NOC2H5OCH3180-181
6With2H5NOCH3OCH3118-123 (Razlog.)
7With2H5NSC2H5OCH3160-165 (Razlog.)
8With2H5NSCH3OCH3146-148
9With2H5NSO2CH3OCH3206-208
10CF3NOC2H5OCH3169-171
11CF3NSC2H5OCH3179-180
12CF3NSCH3OCH3266-267
13CH3NC2H5OCH3172-174
14CH3NN(CH3)2OCH383-185 (Razlog.)
15CH3CH3N(CH3)2OCH3266-268 (Razlog.)
16CH3NOC2H5OCH3168-170 (Razlog.)
17CH3NOCH3OCH3241
18CH3NSC2H5OCH3163-165
19CH3NSCH3OCH3178-180 (Razlog.)
20CH3CH3SCH3OCH3191-193 (Razlog.)
21CH3NSO2CH3OCH3246-248 (Razlog.)
22ClNN(CH3)2OCH3193-195
23ClNOC2H5OCH3168-169
24ClNOC3H7< / br>
(fine arts)
OCH3178-180
25ClNSC2H5OCH3180-182
26ClNSCH3OCH3163-165
27ClNSCH3CH3172-174
28n-C3H7NClOCH3183-188 (Razlog.)
29n-C3H7NN(CH3)2OCH3203-206 (Razlog.)
30n-C3H7NOC2H5OCH3177-178 (Razlog.)
31n-C3H7NSCH3OCH3176-178 (Razlog.)
The connection of comparison 1CH3NNOCH3173-175 (Razlog.)
The connection of comparison 2ClNNOCH3189-190
Table 2
Connection # R1R2XTpl.(°)
32CH3OC2H5OCH3159-164 (Razlog.)
Table 3
Connection # R1R2R3XTpl.(°)
33CH3NOCH3OCH3211-213
34CH3NOC2H5OCH3-185
Table 4
Connection # R1XTpl.(°)
35SO2CH3OCH3190-201

These NMR (DMSO-d6that δ ppm)

Connection # 1

of 1.32 (3H, t, J=7.5 Hz), is 2.37 (3H, s), 3,06 (2H, q, J=7.5 Hz), 3,99 (6N, (C), of 6.02 (1H, s), 7,38 (1H, d, J=9,3 Hz)to 8.14 (1H, d, J=9.3 Hz), 10,55 (1H, s), 13,26 1H, user. C).

Connection # 2

of 1.33 (3H, t, J=7.5 Hz), to 3.09 (2H, q, J=7.5 Hz), 3,99 (6N, C)to 6.00 (1H, s), 7,63 (1H, d, J=9.6 Hz), 8,35 (1H, d, J=9.6 Hz), of 10.58 (1H, user. C), 13,37 (1H, user. C).

Connection # 3

to 1.00 (3H, t), 2,80 is 3.23 (2H, m), 3.96 points (6N, (C), 5,98 (1H, s), 6,93 (1H, d), 7,38 (1H, s), 7,80 (1H, d) or 10.60 (1H, user. C)13,02 (1H, user. C).

Connection # 4

of 1.28 (3H, t, J=7.5 Hz), 2,94 (6N, (C), 2,98 (2H, q, J=7.5 Hz), 3,92 (6N, (C), 6,01 (1H, s), 7,22 (1H, d, J=10.0 Hz), of 7.90 (1H, d, J=10.0 Hz), 10,53 (1H, s), is 12.85 (1H, user. C).

Connection # 5

to 1.24 (3H, t, J=7.0 Hz), is 1.31 (3H, t, J=7.5 Hz), 3,03 (2H, q, J=7.5 Hz), 3,94 (6N, C)to 4.17 (2H, q, J=7.0 Hz), 6,04 (1H, s), 7,11 (1H, d, J=9.7 Hz), to 8.12 (1H, d, J=9.7 Hz), 10,57 (1H, user. C)13,00 (1H, user. C).

Connection # 6

of 1.30 (3H, t, J=7.5 Hz), 3,03 (2H, q, J=7.5 Hz), 3,80 (3H, s), 3,92 (6N, (C), of 6.02 (1H, s), to 7.15 (1H, d, J=9.7 Hz), 8,10 (1H, d, J=9.7 Hz), 10,56 (1H, s), 13,01 (1H, user. C).

Connection # 7: Cm. example of synthesis 2.

Connection # 8

of 1.31 (3H, t, J=7.5 Hz), 2,47 (3H, s), 3,06 (2H, q, J=7.5 Hz), 3,93 (6N, (C), 6,04 (1H, s), 7,45 (1H, d, J=9.6 Hz), of 8.09 (1H, d, J=9.6 Hz), 10,57 (1H, user. C)12,96 (1H, user. C).

Connection # 9

of 1.36 (3H, t, J=7.5 Hz), 3,18 (2H, q, J=7.5 Hz), 3,26 (3H, s), 3,95 (6N, (C), of 5.99 (1H, s), to 7.99 (1H, d, J=9.5 Hz), 8,58 (1H, d, J=9.5 Hz), 10,56 (1H, s), 13,34 (1H, user. C).

Connection # 10

to 1.24 (3H, t, J=7.0 Hz), 3,94 (6N, C)4,20 (2H, q, J=7.0 Hz), the 6.06 (1H, s), 7,31 (1H, d, J=9.8 Hz), a 8.34 (1H, d, J=9.8 Hz), 10,70 (1H, user. C), 13,26 (1H, user. C).

Connection # 11

to 1.24 (3H, t, J=7,3 Hz), is 3.08 (2H, q, J=7,3 Hz), 3,94 (6N, C)5,94 (1H, s), 7,58 (1H, d, J=9.6 Hz), of 8.28 (1H, d, J=9.6 Hz), 10,69 (1H, user. C), 13,21 (1H, user. C).

Connection # 12

2,49 (3H, s), 3,93 (6N,s), 6,04 (1H, s), 7,63 (1H, d, J=9.6 Hz), 8,29 (1H, d, J=9.6 Hz), 10,69 (1H, user. C), 13,23 (1H, user. C).

Connection # 13: Cm. example of synthesis 1.

Connection # 14

to 2.55 (3H, s), 2,94 (6N, (C), 3,92 (6N, C)to 6.00 (1H, s), 7,21 (1H, d, J=9.9 Hz), the 7.85 (1H, d, J=9.9 Hz), 10,52 (1H, user. C)is 12.85 (1H, user. C).

Connection # 15

the 2.46 (3H, s)to 2.55 (3H, s), 2,92 (6N, (C), 3,92 (6N, (C), of 6.02 (1H, s), 7,10-7,11 (1H, m), 10,52 (1H, s), 12,83 (1H, s).

Connection # 16

of 1.26 (3H, t, J=7.5 Hz), 2.63 in (3H, s), 3.96 points (6N, (C), is 4.21 (2H, q, J=7.5 Hz), of 6.02 (1H, s), 7,11 (1H, d, J=9.9 Hz), 8,10 (1H, d, J=9.9 Hz), 10,54 (1H, user. C)13,00 (1H, user. C).

Connection # 17

2,60 (3H, s), 3,81 (3H, s), 3,92 (6N, (C), 6,01 (1H, s), 7,14 (1H, d, J=9.7 Hz), 8,10 (1H, d, J=9.7 Hz), 10,56 (1H, user. C)13,01 (1H, user. C).

Connection # 18

of 1.23 (3H, t, J=7.5 Hz), 2.63 in (3H, s), is 3.08 (2H, q, J=7.5 Hz), 3,95 (6N, (C), of 5.99 (1H, s), 7,35 (1H, d, J=9.6 Hz), 8,02 (1H, d, J=9.6 Hz), 10,50 (1H, user. C)12,90 (1H, user. C).

Connection # 19

Connection # 20

of 2.44 (3H, s)of 2.50 (3H, s), 2,62 (3H, s), 3,93 (6N, (C), 6,03 (1H, s), 7,32 (1H, s), 10,56 (1H, s), 12,93 (1H, s).

Connection # 21

of 2.75 (3H, s), or 3.28 (3H, s), 3.96 points (6N, (C), 5,98 (1H, s), 7,98 (1H, d, J=9.0 Hz), 8,56 (1H, d, J=9.0 Hz), 10,53 (1H, user. C), 13,31 (1H, user. C).

Connection # 22

2,97 (6N, (C), 3,92 (6N, (C), 5,96 (1H, s), 7,26 (1H, d, J=10.0 Hz), 7,88 (1H, d, J=10.0 Hz), 10,50 (1H, user. C)12,90 (1H, user. C).

Connection # 25

to 1.24 (3H, t, J=7,3 Hz), of 3.07 (2H, q, J=7,3 Hz), 3,94 (6N, (C), 6,04 (1H, s), 7,52 (1H, d, J=9.6 Hz), to 8.12 (1H, d, J=9.6 Hz), 10,67 (1H, user. C)13,10 (1H, user. C).

Connection # 26

2,47 (3H, s), 3,93 (6N, (C), 6,03 (1H, s), EUR 7.57 (1H, d, J=9.6 Hz), 8,13 (1H, d, J=9.6 Hz), 10,65 (1H, user. C), 13,12 (1H, user. C)./p>

Connection # 27

2,39 (3H, s), 2,48 (3H, s)to 3.92 (3H, s), to 6.58 (1H, s), 7,53 (1H, d, J=9.5 Hz), 8,10 (1H, d, J=9.5 Hz), a 10.74 (1H, user. C)of 13.75 (1H, user. C).

Connection # 28

and 0.98 (3H, t, J=7.4 Hz), 1,7-1,9 (2H, m), totaling 3.04 (2H, t, J=7.4 Hz), 3,99 (6N, (C), 6,01 (1H, s), 7,63 (1H, d, J=9.5 Hz), 8,35 (1H, d, J=9.5 Hz), of 10.58 (1H, s), 13,38 (1H, s).

Connection # 29

of 0.95 (3H, t, J=7,3 Hz), 1,7-1,9 (2H, m), of 2.9-3.0 (8H, m), 3,92 (6N, (C), 6,03 (1H, s), 7.23 percent (1H, d, J=10.0 Hz), of 7.90 (1H, d, J=10.0 Hz), 10,54 (1H, s), and 12.9 (1H, s).

Connection # 30

to 0.97 (3H, t, J=7,3 Hz)to 1.22 (3H, t, J=7,1 Hz), 1,7-1,9 (2H, m), 2,98 (2H, t, J=7.4 Hz), 3,93 (6N, C)to 4.15 (2H, q, J=7.0 Hz), equal to 6.05 (1H, s), 7,12 (1H, d, J=9.7 Hz), 8,13 (1H, d, J=9.7 Hz), of 10.58 (1H, ), 13,0 (1H, s).

Connection # 31

to 0.97 (3H, t, J=7,3 Hz), 1,7-1,9 (2H, m), of 2.45 (3H, s)of 3.00 (2H, t, J=7.5 Hz), 3,93 (6N, C), equal to 6.05 (1H, s), 7,45 (1H, d, J=9.6 Hz), of 8.09 (1H, d, J=9.5 Hz), of 10.58 (1H, s), 12,9 is 13.0 (1H, user. C).

Compound No. 32: Cm. example of synthesis 3.

Example of synthesis 4

Synthesis of 1-(2-chloro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl)-3-(4,6-dimethoxypyrimidine-2-yl)urea (compound No. 38)

2-Chloro-6-n-propylimidazol[1,2-b]pyridazin-3-ylsulphonyl (0,49 g, 1.78 mmol), phenyl N-(4,6-dimethoxypyrimidine-2-yl)carbamate (0.55 g, 2 mmol) and acetonitrile (5 ml) was placed in 25-ml flask with a form of eggplant, stirred at room temperature and to this mixture is added DBU (0.31 g, 2 mmol) in one portion and the mixture is stirred at room temperature for 3 hours. After the reaction finished, the reaction solution was pouring out of the t in water (50 ml) and the pH adjusted to about 2 with diluted hydrochloric acid, the resulting crystals are formed. The crystals are collected by filtration, washed with water, acetone and ether in this order and dried under reduced pressure, obtaining mentioned in the title compound as light brown crystals. The output is equal to 0.71 g (89.5 per cent).

Tpl.=199-201°C (decomp.)

1H NMR (DMSO-d6that δ): 0,70 (3H, t, J=7,3 Hz), 1,4-1,5 (2H, m), 2,6-2,7 (2H, m), 3,97 (6N, (C), between 6.08 (1H, s), EUR 7.57 (1H, d, J=9.4 Hz), compared to 8.26 (1H, d, J=9.4 Hz), is 10.68 (1H, user. C)to 13.4 to 13.5 (1H, m).

IR (nujol, cm-1): 3643, 1720, 1703, 1607, 1573, 1453, 1359, 1324, 1290, 1199, 1162, 1016, 888, 840, 629, 589, 514.

Compound No. 36, 37 and 39-52, shown in the following table 5 are synthesized in the same manner as described above. The table also shows the above-described compound No. 38.

Table 5
Connection # R1R2R3XTpl.(°)
36CH3Nn-C3H7OCH3180-184 (Razlog.)
37ClNWith2H5OCH3162-166
38ClNn-C3 H7OCH3199-201 (Razlog.)
39CH3NISO-C3H7OCH3164-165 (Razlog.)
40ClNISO-C3H7OCH3197-199
41ClNn-C4H9OCH3164-167
42ClNISO-C4H9OCH3171-174
43ClNCH2=SNOCH3140-144
44ClNC-C3H5OCH3166-169
45ClN(E)-CH3SN=SNOCH3170-174
46FNn-C3H7OCH3177,3-178,5
47CNNn-C3H7OCH3167,6-170,0
48SC2H5Nn-C3H 7OCH3169,9-170,4
49SO2C2H5Nn-C3H7OCH3228,4-to 230.8
50ClH(E)-Cl-CH=CHOCH3170,0-172,5
51ClN(Z)-Cl-CH=CHOCH3171,0-174,0
52ClNHC≡OCH3>200 (Razlog.)

These NMR (DMSO-d6that δ ppm)

Connection # 36

of 0.71 (3H, t, J=7.4 Hz), 1,4-1,5 (2H, m), 2,6-2,7 (5H, m), 3,97 (6N, C), equal to 6.05 (1H, s), the 7.43 (1H, d, J=9.4 Hz), 8,15 (1H, d, J=9.4 Hz), 10,5 to 10.6 (1H, usher.), of 13.2 and 13.3 (1H, usher.).

Connection # 37

of 1.02 (3H, t, J=7.5 Hz), 2,70 (2H, q, J=7.5 Hz), 3.96 points (6N, (C), the 6.06 (1H, s), 7,58 (1H, d, J=9.4 Hz), compared to 8.26 (1H, d, J=9.4 Hz), 10,66 (1H, user. C)13,39 (1H, user. C).

Compound No. 38: Cm. example of synthesis 4.

Compound No. 39

1,09 (6N, d, J=6,9 Hz)of 2.64 (3H, s), 2,96 (1H, Sept, J=6.9 Hz), 3,95 (6N, (C), 6,04 (1H, s), 7,51 (1H, d, J=9.4 Hz), 8,17 (1H, d, J=9.4 Hz), 10,56 (1H, user. C)to 13.1 and 13.2 (1H, usher.).

Connection # 40

1,09 (6N, d, J=7,0 Hz), 2,97 (1H, Sept, J=7.0 Hz), 3,95 (6N, (C), the 6.06 (1H, s), the 7.65 (1H, d, J=9.5 Hz), of 8.28 (1H, d, J=9.5 Hz), 10,66 (1H, user. C), 13,31 (1H, user. C).

Connection # 41

of 0.71 (3H, t, J=7.4 Hz), 1,09 (2H, Sextus, J=7,4 Hz)of 1.39 (2H, TT, and 7.7, 7.4 Hz), to 2.66 (2H, t, J=7,7 Hz), 3,97 (6N, (C), 6,07 (1H, s),7,58 (1H, d, J=9.4 Hz), compared to 8.26 (1H, d, J=9.4 Hz), is 10.68 (1H, user. C)13,42 (1H, user. C).

Connection # 42

0,66 (6N, d, J=6.6 Hz), a 1.88 (1H, m), 2,53 (2H, d, J=7,4 Hz), 3,97 (6N, C)6,09 (1H, s), 7,56 (1H, d, J=9.4 Hz), compared to 8.26 (1H, d, J=9.4 Hz), is 10.68 (1H, user. C)13,42 (1H, user. C).

Connection # 43

3,96 (6N, (C), 5,77 (1H, d, J=11,0 Hz), equal to 6.05 (1H, s), 6.35mm (1H, d, J=17,7 Hz), to 6.58 (1H, DD, J=17.7 and, of 11.0 Hz), of 7.97 (1H, d, J=9.6 Hz), 8,32 (1H, d, J=9.6 Hz), to 10.62 (1H, user. C), 13,34 (1H, user. C).

Connection # 44

0,75-0,90 (2H, m), 0,90-of 1.05 (2H, m), 2.05 is-to 2.15 (1H, m), 3.96 points (6N, (C), the 6.06 (1H, s), 7,53 (1H, d, J=9.5 Hz), 8,19 (1H, d, J=9.5 Hz), at 10.64 (1H, user. C), 13,21 (1H, user. C).

Connection # 45

to 1.83 (3H, DD, J=6,8, and 1.6 Hz), 3,97 (6N, (C), 6,10 (1H, s), of 6.20 (1H, DQC, J=16,0, and 1.6 Hz), 6,83 (1H, DQC, J=16,0, 6,8 Hz), to 7.84 (1H, d, J=9.6 Hz), of 8.25 (1H, d, J=9.6 Hz), as 10.63 (1H, user. C)made 13.36 (1H, user. C).

Connection # 46

to 0.72 (3H, t, J=7,3 Hz)to 1.48 (2H, m)to 2.67 (2H, t, J=7,6 Hz), 3,97 (6N, (C), the 6.06 (1H, s), 7,60 (1H, d, J=9.4 Hz), of 8.27 (1H, d, J=9.4 Hz), 10,66 (1H, s), 13,40 (1H, s).

Connection # 47

to 0.73 (3H, t, J=7,4 Hz)and 1.51 (2H, m), a 2.71 (2H, t, J=7,6 Hz), 3,97 (6N, (C), between 6.08 (1H, s), 7,66 (1H, d, J=9.5 Hz), 8,40 (1H, d, J=9.5 Hz), is 10.75 (1H, user. C), the 13.4-13.8V (1H, usher.).

Connection # 48

of 0.68 (3H, t, J=7,3 Hz)to 1.37 (3H, t, J=7,3 Hz), USD 1.43 (2H, m), 2,58 (2H, t, J=7,7 Hz), 3,23 (2H, q, J=7,3 Hz), 3.96 points (6N, (C), the 6.06 (1H, s), 7,45 (1H, d, J=9.3 Hz), 8,18 (1H, d, J=9.3 Hz), 10,57 (1H, s), 13,24 (1H, s).

Connection # 49

to 0.72 (3H, t, J=7,3 Hz)of 1.18 (3H, t, J=7,3 Hz)to 1.45 (2H, m)to 2.65 (2H, t, J=7.9 Hz), 3,74 (2H, q, J=7,3 Hz), 3,98 (6N, (C), 6,11 (1H, s), 7,66 (1H, d, J=9.4 Hz), to 8.45 (1H, d, J=9.4 Hz), 10,77 (1H, s), 13,60 (1H, s).

Connection # 50

3,96 (6N, C)6,09 (1H, s), of 6.73 (1H, d, J=13,7 Hz), 7,60 (1H, d, J=13,7 Hz), and 7.8 (1H, d, J=9.6 Hz), at 8.36 (1H, d, J=9.6 Hz), 10,61 (1H, user. C), 13,31 (1H, user. C).

Connection # 51

3,94 (6N, (C), 6,03 (1H, s), 6,85 (1H, d, J=8,2 Hz), 7,01 (1H, d, J=8,2 Hz), 7,92 (1H, d, J=9.5 Hz), scored 8.38 (1H, d, J=9.5 Hz), to 10.62 (1H, user. C), 13,21 (1H, user. C).

Connection # 52

3,99 (6N, (C), to 4.81 (1H, s), 5,98 (1H, s), 7,71 (1H, d, J=9.4 Hz), of 8.37 (1H, d, J=9.4 Hz), at 10.64 (1H, user. C)13,52 (1H, user. C).

Preparative example 1

10.6 parts of compound No. 23 of table 1, 5 parts of ethylene glycol, 0.1 part of butylparaben, 0.2 part of a silicone emulsion (Antifoam E20, Kao Corporation), 0.5 parts of colloidal, water-containing aluminium silicate (Kunipia F, Kunimine Kogyo Co., Ltd.), 0.3 part of sodium carboxymethylcellulose (Cellogen 7A, Dai-ichi Kogyo Seiyaku Co., Ltd.), 1 part of sulphate allylanisole ester polyoxyalkylene (Neugen EA-177, Dai-ichi Kogyo Seiyaku Co., Ltd.), 1 part districtkemerovo ester polyoxyalkylene (New Cargen FS-7, Takemoto Oil &Fat Co., Ltd.), 0.5 parts of glycerol complex ester of rosin (Solpoal 7518, Toho Chemical Industry Co., Ltd) and 20.8 parts of water are mixed and pulverized in wet conditions the mill, Dynomill KDL (Sinmal Enterprise), obtaining a homogeneous suspension, and then there was added 2 parts of a condensate of sodium naphthalenesulfonate (New Cargen PS-P, Takemoto Oil &Fat Co., Ltd.), 2 parts of didecyldimethylammonium chloride (Catiogen DDM, Dai-ichi Kogyo Seiyaku Co., Ltd.), 15 parts of monolaurate of polyoxyethylene (Emanon 1112, Kao Corporation) and 41 of the water, getting a homogeneous fluid medium.

Preparative example 2

10.6 parts of compound No. 37 from table 5, 5 parts is etilenglikola, 0.1 part of butylparaben, 0.2 part of a silicone emulsion (Antifoam E20, Kao Corporation), 0.5 parts of colloidal, water-containing aluminium silicate (Kunipia F, Kunimine Kogyo Co., Ltd.), 0.3 part of sodium carboxymethylcellulose (Cellogen 7A, Dai-ichi Kogyo Seiyaku Co., Ltd.), 1 part of sulphate allylanisole ester polyoxyalkylene (Neugen EA-177, Dai-ichi Kogyo Seiyaku Co., Ltd.), 1 part districtkemerovo ester polyoxyalkylene (New Cargen FS-7, Takemoto Oil &Fat Co., Ltd.), 0.5 parts of glycerol complex ester of rosin (Solpoal 7518, Toho Chemical Industry Co., Ltd) and 20.8 parts of water are mixed and pulverized in wet conditions the mill, Dynomill KDL (Sinmal Enterprise), obtaining a homogeneous suspension, and then there was added 2 parts of a condensate of sodium naphthalenesulfonate (New Cargen PS-P, Takemoto Oil &Fat Co., Ltd.), 2 parts of didecyldimethylammonium chloride (Catiogen DDM, Dai-ichi Kogyo Seiyaku Co., Ltd.), 12 parts of monolaurate of polyoxyethylene (Emanon 1112, Kao Corporation) and 44 parts of water, getting a homogeneous fluid medium.

Preparative example 3

10.6 parts of compound No. 44 from table 5, 10 parts of ethylene glycol, 0.1 part of butylparaben, 0.2 part of a silicone emulsion (Antifoam E20, Kao Corporation), and 0.8 parts of colloidal, water-containing aluminium silicate (Kunipia F, Kunimine Kogyo Co., Ltd.), 2 parts of sulphate allylanisole ester polyoxyalkylene (Neugen EA-177, Dai-ichi Kogyo Seiyaku Co., Ltd), 2 parts districtkemerovo ester polyoxyalkylene (New Cargen FS-7, Takemoto Oil &Fat Co., Ltd.), 1 part glycerin complex ester of rosin (Solpoal 7518, TohoChemical Industry Co., Ltd) and 73.3 parts of water are mixed and pulverized in wet conditions the mill, Dynomill KDL (Sinmal Enterprise), obtaining a homogeneous suspension (fluid medium).

Preparative example 4

Mix 1.1 connection part No. 38 of table 5, 30 parts of bentonite (Kunigel V2, Kunimine Kogyo Co., Ltd.), 66,4 parts of calcium carbonate (Tancal O-430, Asahi Komatsu Co., Ltd.), 2 parts of sodium polyacrylate (Toxanon GR-31A, Sanyo Chemical Industries, Ltd.) and 0.5 parts of dioctylsulfosuccinate sodium (Sanmoline OT, Sanyo Chemical Industries, Ltd.), add water and knead the mixture. After this mixed product ekstragiruyut and granularit through sieves with a diameter of 1.2 mm and dried at 60°receiving granules having a particle diameter of from 0.5 to 1.7 mm

Test example 1

5 cm·5 cm Jiffy Pot™ put the soil for cultivation of paddy rice, then in each pot add water, sow and grow within the prescribed period under the conditions of irrigation, seed, sensitive to the herbicide on the basis of sulfonylurea Scirpus juncoides var. ohwianus, sensitive to the herbicide on the basis of sulfonylurea Lindernia procumbens (Krock.) Philcox, sensitive to the herbicide on the basis of sulfonylurea Lindernia dubia subsp. major Pennell, herbicide on the basis of sulfonylurea Scirpus juncoides var. ohwianus, herbicide on the basis of sulfonylurea Lindernia procumbens (Krock.) Philcox and herbicide on the basis of sulfonylurea Lindernia dubia subsp. major Pennell. When the plant is I reached the stage of emergence of the second sheet, the prescribed amount Jiffy Pot, where they grow plants, transferred into a 150-cm2rectangular plastic container, add water up to a height of 3 cm and a capacity of add chemical diluent containing compound, in the amount of 1 g/ar. Chemical thinner receive, dissolving 1.5 g of the compound in 2 l of N,N-dimethylformamide (DMF)containing 2% (m/Rev) surfactants Tween™ 20, and then diluting it with water, bringing the total volume to 10 liters

Three weeks after handling chemical substance assess the effect on every weed on the criteria shown in table 6.

Table 6
IndexEffectThe degree of suppression (herbicide ratio), %
0No0
1Very minorfrom 1 to 20
2Minorfrom 21 to 40
3Averagefrom 41 to 60
4Highfrom 61 to 80
5Superbfrom 81 to 100

The results are shown in tables 7 and 8.

Table is CA 7
Connection

No.
S

cirpus

juncoides

var.

ohwianus
S

Lindernia

procumbens

(Krock.)

Philcox
S

Lindernia dubia

subsp.

major

Pennell
R

Scirpus

juncoides var.

ohwianus
R

Lindernia

procumbens

(Krock.)

Philcox
R

Lindernia dubia

subsp.

major

Pennell
3555555
4555535
7555534
8555555
955 5535
1155555
12555535
13555555
14555534
16555545
18555555
195 55554
2355554
2555554
26555534
3155554
344545
35555535
From the Association

comparison

1
555201
Connection

comparison

2
555000
Table 8
Connection

No.
S

Scirpus

juncoides var.

ohwianus
S

Lindernia

procumbens

(Krock.)

Philcox
S

Lindernia dubia

subsp.

major

Pennell
R

Scirpus

juncoides var.

ohwianus
R

Lindernia

procumbens

(Krock.)

Philcox
R

Lindernia dubia

subsp.

major

Pennell
36555555
37555555
38 555555
39555555
40555555
41555545
4355545
4455545
455554 5
4655555
S: sensitive to the herbicide on the basis of sulfonylurea;

Scirpus juncoides var. ohwianus and Lindernia procumbens (Krock.) Philcox produced in Kyoto Prefecture; and

Lindernia dubia subsp. major Pennell made in Makabe, Ibaraki Prefecture.

R: herbicide on the basis of sulfonylurea;

Sciprus juncoides var. ohwianus produced in Iwamizawa in Hokkaido;

Lindernia procumbens (Krock.) Philcox produced in Tajiri, Miyagi Prefecture; and

Lindernia dubia subsp. major Pennell produced in Kawanishi, Prefecture Yamagata.

INDUSTRIAL APPLICABILITY

The herbicide of the present invention can be used to control weeds, including weeds resistant to the herbicide on the basis of sulfonylureas on the fields of rice-paddy, and can also be used to reduce the number of active ingredients in the combination product.

1. Herbicide for weeds resistant to the herbicide on the basis of sulfonylureas, including the compound represented by the formula

where Q is a condensed heterocyclic group represented by the formula

where R1 represents a halogen atom, optionally halogenated lower alkyl group, lower alkylsulfonyl group;

R2 represents a hydrogen atom;

R3 represents a lower alkyl group, lower cycloalkyl group, lower alkylamino group, lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, a lower alkylamino or lower dialkylamino;

X represents a lower alkyl group or lower CNS group and Y represents a lower CNS group.

2. The herbicide according to claim 1, where R1 represents a halogen atom, optionally halogenated lower alkyl group, or lower alkylsulfonyl group, R3 represents a lower alkyl group, lower cycloalkyl group, lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, a lower alkylamino or lower dialkylamino, and X and Y each represent a lower CNS group.

3. The herbicide according to claim 1, where R1 represents a halogen atom or an optionally halogenated lower alkyl group, R2 represents a hydrogen atom, R3 represents a lower alkyl group, NISS the Yu cycloalkyl group, lower CNS group, a lower allylthiourea, lower alkylsulfonyl group, a lower alkylamino or lower dialkylamino, and X represents a lower alkyl group or lower CNS group and Y represents a lower CNS group.

4. The herbicide according to claim 1, where Q is a condensed heterocyclic group represented by the above formula Q1 or Q4.

5. The compound represented by the formula

where R1 represents a halogen atom or an optionally halogenated lower alkyl group, R2 represents a hydrogen atom, R3 represents a C2-4alkyl group or a lower cycloalkyl group, and X represents a lower alkyl group or lower CNS group and Y represents a lower CNS group.

6. The compound according to claim 5, where R1 represents a halogen atom, R3 represents a C2-4kilou group or lower cycloalkyl group, and X and Y each represent a methoxy group.

7. Herbicide for weeds resistant to the herbicide on the basis of sulfonylureas, including the compound described in item 5.

8. Herbicide for weeds resistant to the herbicide on the basis of sulfonylureas, including the compound described in item 6.

9. The herbicide on Liu the WMD one of claims 1 to 4, 7 and 8, which has a significant effect on the weeds, herbicide on the basis of sulfonylureas.

10. Method of weed control, herbicide on the basis of sulfonylureas, which includes applying a herbicide according to any one of claims 1 to 4, 7 and 8.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to triheterocyclic compound of the formula (I): wherein X represents carbon atom; Y represents carbon or nitrogen atom; W represents carbon or nitrogen atom; U represents -CR2, and Z represents -CR2 or nitrogen atom; ring A represents (C5-C6)-cycloalkyl ring or 5-membered heterocyclic ring comprising one nitrogen, oxygen or sulfur atom; R1 represents alkyl, alkenyl, alkynyl, -NR4R5, -OR6 and others; R3 represents phenyl ring substituted with 1-3 substitutes or pyridyl or 1,3-dioxoindanyl ring substituted with 1-2 substitutes, and its pharmaceutically acceptable salts and pharmaceutical composition containing thereof as an active component. Also, invention relates to derivatives of pyrazolopyrimidine and derivatives of pyrrolopyrimidine. Compounds of the formula (I) show antagonistic activity with respect to corticotropin-releasing factor receptors. The compound can be used in treatment and/or prophylaxis of depression, anxiety state, disorders in food intake, post-traumatic stress, ulcerous disease, irritable bowel syndrome, Alzheimer's disease, abuse in drugs using or alcoholic syndrome dependence.

EFFECT: valuable medicinal properties of compounds and pharmaceutical agent.

7 cl, 1 dwg, 24 ex

FIELD: pharmacology, medicine.

SUBSTANCE: invention relates to new mercaptoacetylamide derivatives, which represents angiotensine converting enzyme and neutral endopeptidase inhibitors and useful in treatment of cardiovascular condition. More particularly invention relates to derivatives of formula I , wherein R1 represents hydrogen or acyl; wherein R2 represents hydrogen or biphenylmethyl; { represents -(CH2)n (n = 1, integer); B1 and B2 are independently hydrogen; or pharmaceutically acceptable salts or stereomers thereof. Method for production of compounds of formula I and formula II, pharmaceutical composition on the base of formula I, method for production thereof and method for treatment of cardiovascular condition.

EFFECT: new derivatives having value biological properties.

14 cl, 3 tbl, 4 ex, 1 dwg

FIELD: organic chemistry, medicine, veterinary science, pharmacy.

SUBSTANCE: invention relates to derivatives of tetrahydropyranyl-cyclopentyl-tetrahydropyridopyridine of the formula (1): , wherein R3 means oxygen atom or absent; R8 is chosen from: (a) hydrogen atom; (b) (C1-C3)-alkyl that can be unsubstituted or substituted with 1-6 fluorine atoms; (c) -O-(C1-C3)-alkyl; (d) fluorine atom, and (e) hydroxy-group, and their pharmaceutically acceptable salts and separate diastereomers. These compounds are modulators of activity of chemokine receptors. Also, invention relates to a pharmaceutical composition based on compounds of the formula (1), method for modulation of activity of chemokine receptors in humans and animals and a method for preparing a medicinal agent. Invention provides preparing novel modulators of chemokine receptors activity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 13 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of pyridazinoquinoline of the formula (II): or their tautomers, or their pharmaceutically acceptable salts wherein ring A represents ortho-condensed phenyl and monosubstituted with R4 wherein R4 means halogen atom; R1 represents -(CH2)nL wherein n means a whole number from 1 to 6; L is chosen from unsubstituted phenyl or its benzo-derivative, or L is chosen from phenyl or its benzo-derivative and substituted with one or two groups chosen from -CN, -CF3, (C1-C4)-alkyl, or L is chosen from -OH, -OCOR', -SOmR' wherein m means 0, 1 or 2, -NR'R'' under condition that -NR'R'' differs from -NH2, -NR'COR'', or L is chosen from heterocycle or heteroaryl wherein in each abovementioned case any group from R' or R'' is chosen from hydrogen atom, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, phenyl, phenyl-(C1-C4)-alkyl and wherein any group from R' or R'' is unsubstituted or substituted 1, 2 or 3 times with phenyl, -OH, O-(C1-C4)-alkyl at carbon atoms wherein in any abovementioned case heterocycle is chosen from five- or six-membered heterocyclic ring comprising 1, 2 or 3 heteroatoms chosen from oxygen (O), nitrogen (N) or sulfur (S) atoms or its condensed benzo-derivative, indicated heterocycle wherein carbon atom is disubstituted to form (C5-C7)-spiro-group and indicated heterocycle wherein carbon atom © is substituted for oxygen atom (O) to form carbonyl group and wherein in any case heteroaryl is chosen from unsubstituted thiophene, furan, imidazole, triazole, tetrazole. Compounds of the formula (II) are antagonists of glycine-receptors and can be used in preparing pharmaceutical agents designated for treatment or prophylaxis of ischemic disease.

EFFECT: valuable medicinal properties of compounds.

5 cl, 8 tbl, 148 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to the substituted pyrazoles, pharmaceutical compositions comprising these compounds and methods for their using in treatment of autoimmune diseases wherein cathepsin S is their mediating agent. Described substituted pyrazoles represent compounds of the formula (I): wherein a dotted line is placed near the group -C-R6 or absent, or it represents a bond; Y represents nitrogen atom or -CR20; Z represents nitrogen atom or -CR21; T represents nitrogen atom or -CR2; S represents nitrogen atom or -CR3 under condition that from 0 to 3 among S, T, Y and Z represent nitrogen atom, and additionally under condition that one among S, T, Y and Z can represent the group =N+-O- if other three are not nitrogen atom; R20 is chosen from hydrogen, halogen atom, hydroxy-, cyano-group, 4-7-membered heterocycle comprising nitrogen and oxygen atom; R21 represents hydrogen atom; R2 is chosen from hydrogen, halogen atom and hydroxy-group; R3 is chosen from hydrogen, halogen atom, (C1-C5)-alkoxy-group, (C1-C5)-alkyl, cyano-group, -RgRhN, 4-7-membered heterocyclyl comprising nitrogen and oxygen atom and -R17OC=O; R5 and R6 represent hydrogen atom; R7 and R8 can be combined in common and form optionally substituted 5-7-membered carbocylic or heterocyclic ring comprising nitrogen atom and wherein the indicated ring can be unsaturated or aromatic and this ring is substituted optionally with -Rt(C=O)- or -RtSO2; Rt represents (C1-C6)-alkyl; Rg, Rh and R17 represent (C1-C5)-alkyl; G represents (C3-C6)-alkanediyl; Ar represents monocyclic aryl ring optionally substituted from 1 to 3 substitutes chosen independently from halogen atom, (C1-C5)-alkyl and (C1-C5)-halogenalkyl; R32 represents hydrogen atom, (C1-C5)-alkyl, cyano-group, C1-C5)-hydroxyalkyl, -(C=O)NRvRx, -CHO or (C1-C6)-alkoxycarbonyl wherein each from Rv and Rx is chosen independently from hydrogen atom (H), (C1-C5)-alkyl, (C1-C5)-hydroxyalkyl, (C1-C5)-heterocyclyl comprising nitrogen and oxygen atom, (C1-C5)-heterocyclyl comprising nitrogen and oxygen atom-(C1-C5)-alkylene, (C1-C5)-aminoalkylene; Q represents -NR33, sulfur (S) or oxygen (O) atom; R33 represents hydrogen atom, (C1-C5)-alkyl, (C2-C5)-heterocyclyl comprising oxygen atom-(C1-C5)-alkylene, -R35OC=O and -R35OC=O; R35 represents (C1-C5)-alkyl, or their pharmaceutically acceptable salts, amides and esters, or their stereoisomeric forms.

EFFECT: improved for inhibition, valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

25 cl, 3 tbl, 135 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to bicyclic heterocyclic substituted phenyloxazolidinones that represent compounds of the formula (I): wherein R is taken from the group consisting of -OH, O-heteroaryl, -N3, -OSO2R'', -NR'''R'''', or the formula: wherein: (ii) R'' represents direct or branched alkyl comprising up to 5 carbon atoms; (iii) R''' and R'''' are taken independently from the group consisting of hydrogen atom (H), -CO2-R1, -CO-R1, -CS-R1 and -SO2-R4 wherein R1 is taken among the group consisting of cycloalkyl comprising from 3 to 6 carbon atoms and direct or branched alkyl comprising up to 6 carbon atoms; R4 is taken from direct or branched alkyl comprising up to 4 carbon atoms; and R4a represents -CN or -NO2; R4b represents -SR4c, amino-group, -NHR4c or -NR4cR4d wherein R4c and R4d are taken independently from hydrogen atom (H) or alkyl; X represents from 0 to 4 members taken independently from the group consisting of halogen atom; and Y represents radical of the formula (II): or (III): wherein R5, R6, R7 and R8 represent independently hydrogen atom (H), or R and R6 and/or R7 and R8 form in common oxo-group; R9 and R10 represent independently hydrogen atom (H); A, B, C and D are taken from carbon atom (C) and nitrogen atom (N) to form phenyl ring or 5-6-membered heteroaromatic ring wherein the indicated heteroaromatic ring comprises from 1 to 4 members taken from the group consisting of nitrogen atom (N); Z is taken from alkyl, heteroaryl comprising nitrogen atom (N); and m represents 0 or 1. These compounds are useful as antibacterial agents and can be used for treatment of patient with the state caused the bacterial infection or with the bacterial infection caused by S. aureus and E. faecium.

EFFECT: valuable medicinal properties of compounds.

45 cl, 1 tbl, 50 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to derivatives of carboline of the general formula (I): wherein R3 means hydrogen atom (H), hydroxyl (OH), -O-(C1-C6)-alkyl; R4 means -N(R17)2 wherein R17 means hydrogen atom (H), (C1-C6)-alkyl, -C(O)-phenyl, -C(O)-(C1-C10)-alkyl, -S(O)y-R14 wherein y = 0, 1 or 2; R14 means (C1-C6)-alkyl, phenyl substituted with halogen atom; or R means amino-group (-NH2), -NH-C(O)-R15 wherein R15 means pyrrolidine, pyrazolidine, furan, pyridine, pyrazine, imidazoline, isoxazolidine, 2-isoxaline, thiophene possibly substituted with -CF3 or (C1-C6)-alkyl; (C3-C7)-cycloalkyl, -N(R13)2 wherein R12 means hydrogen atom (H) or phenyl under condition that -N(R13)2 doesn't mean -NH2; phenyl possibly substituted with (C1-C6)-alkyl, -CF3 if two substituted at phenyl form dioxalane ring; R5 means hydrogen atom (H), or R and R5 in common with nitrogen atom (N) form a heterocycle. Also, invention describes a method for their preparing. Compounds of the formula (I) are suitable for preparing medicinal agents used in prophylaxis and treatment of diseases wherein the enhanced activity of 1 κB is involves.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

6 cl, 2 tbl, 83 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of tetrahydropyridine of the formula (I): wherein (a) means unsubstituted phenyl group or phenyl group substituted with 1, 2 or 3 substitutes chosen independently among (C1-C4)-alkoxy-group, or (b) means unsubstituted indolyl group; R1 and R2 are similar or different and mean hydrogen atom, (C1-C4)-alkyl or phenyl group; X means alkylene group with a direct chain comprising 5, 6, 7 carbon atoms, and to their pharmaceutically acceptable salts also. Also, invention relates to a pharmaceutical composition possessing the inhibitory activity with respect to HDAC based on these compounds. Invention provides new compounds and pharmaceutical composition based on thereof for aims the stimulation of anti-proliferative effect in warm-blooded animals, such as humans.

EFFECT: valuable medicinal properties of compounds and composition.

4 cl, 1 tbl, 9 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for preparing substituted imidazopyridine of the general formula (1): wherein R1 means (C1-C6)-alkoxy-group or -NH2. Method involves interaction of compound of the formula (2): with 3-halogen-2-butanone in cyclohexanone medium at temperature 80-100°C. Using cyclohexanone as a solvent allows reducing the process period and to enhance the yield of the end product.

EFFECT: improved preparing method.

9 cl, 19 ex

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing a pharmaceutically active compound 3-{2-[4-(6-fluorobenzo[d]isoxazole-3-yl)piperidine-1-yl]ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-4-one (risperidone) of the formula (I): that possesses the neuroleptic properties. Method involves the condensation reaction of (2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-yl)acetaldehyde of the formula (II): with (6-fluoro-3-piperidinyl)-1,2-benzisoxazole of the formula (IV): to yield intermediate enamine representing 3-{2-[4-(6-fluorobenzo[d]isoxazole-3-yl)piperidine-1-yl]vinyl}-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-4-one of the formula (III): and the following reduction of this enamine in the presence of hydride. Also, invention claims intermediate compounds of the formula (II) and formula (III) and describes a method for preparing compound of the formula (II) comprising oxidation of 3-(2-hydroxyethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-4-one of the formula (X): Method is characterized by high reproducibility in large-scale manufacturing and represents the unique combination of the synthesis simplicity, decreased cost, safety and protection of the environment.

EFFECT: improved preparing method.

9 cl, 3 ex

FIELD: organic chemistry, insecticides, agriculture.

SUBSTANCE: invention describes a method for protection of seedlings or plants grown from them against insects. Method involves contacting seeds with compound of the formula (I)

or its salt taken in the effective amount and acceptable for agriculture wherein A and B represent oxygen atom (O); R1 represents hydrogen atom (H); R2 represents H; R3 represents (C1-C6)-alkyl; R4 represents (C1-C6)-alkyl or -CN; R5 represents H or halogen atom; R6 represents (C1-C6)-halogenalkyl or halogen atom; R7 represents pyridinyl substituted with from one to three substitutes chosen independently from R9; R8 represents H; each R9 represents independently halogen atom; Also, invention describes a composition covering seedling that comprises compound of the formula (I) by cl. 1 or its salt as a biologically active agent and taken in the effective amount, film-forming agent or adhesive agent. Invention provides effective treatment of seedlings for protection against insects being not only seedlings but also plants at later stages of their growth.

EFFECT: valuable properties of composition, improved method of treatment.

16 cl, 39 tbl, 31 ex

FIELD: fungicides.

SUBSTANCE: invention relates to fungicide composition containing 2,6-dichloro-N-{[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl}-benzamide (compound I) and mankozeb (compound II), and method for treatment or prophylaxis controlling of phytopathogenic fungi of agriculture cultures using the said composition. Product containing compound I and compound II in weight ratio of from 1/100 to 5/1 also is disclosed.

EFFECT: fungicide composition of high efficiency.

9 cl, 1 tbl, 1 ex

FIELD: agriculture, pest control.

SUBSTANCE: the suggested covering for pest control is made of polymeric material and includes, at least, two layers: the upper layer and the lower one, moreover, the lower layer contains a herbicide and one or more pesticides chosen out of the group pf fungicides and insecticides, as for the upper layer, it contains insecticide and/or fungicides not obligatory. The method deals with applying the above-mentioned covering upon the ground and making incisions in the sites for further planting the seedlings. Polymeric composition contains a herbicide to obtain polymeric covering. The innovation enables to provide high-efficient protection and safety of plants.

EFFECT: higher efficiency of plant protection.

28 cl, 3 dwg, 5 ex, 4 tbl

FIELD: agriculture, pest control.

SUBSTANCE: the suggested covering for pest control is made of polymeric material and includes, at least, two layers: the upper layer and the lower one, moreover, the lower layer contains a herbicide and one or more pesticides chosen out of the group pf fungicides and insecticides, as for the upper layer, it contains insecticide and/or fungicides not obligatory. The method deals with applying the above-mentioned covering upon the ground and making incisions in the sites for further planting the seedlings. Polymeric composition contains a herbicide to obtain polymeric covering. The innovation enables to provide high-efficient protection and safety of plants.

EFFECT: higher efficiency of plant protection.

28 cl, 3 dwg, 5 ex, 4 tbl

FIELD: agriculture, pest control.

SUBSTANCE: the suggested covering for pest control is made of polymeric material and includes, at least, two layers: the upper layer and the lower one, moreover, the lower layer contains a herbicide and one or more pesticides chosen out of the group pf fungicides and insecticides, as for the upper layer, it contains insecticide and/or fungicides not obligatory. The method deals with applying the above-mentioned covering upon the ground and making incisions in the sites for further planting the seedlings. Polymeric composition contains a herbicide to obtain polymeric covering. The innovation enables to provide high-efficient protection and safety of plants.

EFFECT: higher efficiency of plant protection.

28 cl, 3 dwg, 5 ex, 4 tbl

FIELD: agriculture, herbicides.

SUBSTANCE: invention relates to aqueous herbicidal concentrate compositions containing glyphosate or salt thereof dissolved in aqueous medium,, surfactant in solution or in form of stable suspension, emulsion or dispersion in said medium, oxalic acid or salt thereof wherein ratio of surfactant and oxalic acid or salt thereof is from 5:1 to 40:1 and ratio of glyphosate or salt thereof based on acidic equivalent and oxalic acid or salt thereof is from 2:1 to 125:1. Also disclosed are method for reducing of surfactant content in said composition including dilution thereof with water; method for suppression of imopea growth by applying of aqueous composition on imopea leaves, as well as solid herbicidal concentrate composition containing glyphosate ammonium salt, oxalic acid or salt thereof and surfactant.

EFFECT: compositions of increased effectiveness.

21 cl, 191 tbl, 99 ex

FIELD: organic chemistry, pesticides.

SUBSTANCE: invention relates to concentrated pesticide solution, containing 0.5-50 mass/vol.% one or more water insoluble pesticides and lignin in mass ratio lignin/pesticide of 1:10-1:1, dissolved in polar solvent mixable with water in amount to adjust total volume to 100 %. Dispersed in water concentrated pesticide solution is applied onto pests or locus thereof.

EFFECT: storage stable products.

9 cl, 7 tbl, 2 ex

FIELD: organic chemistry, pesticides.

SUBSTANCE: invention relates to concentrated pesticide solution, containing 0.5-50 mass/vol.% one or more water insoluble pesticides and lignin in mass ratio lignin/pesticide of 1:10-1:1, dissolved in polar solvent mixable with water in amount to adjust total volume to 100 %. Dispersed in water concentrated pesticide solution is applied onto pests or locus thereof.

EFFECT: storage stable products.

9 cl, 7 tbl, 2 ex

FIELD: organic chemistry, pesticides.

SUBSTANCE: invention relates to concentrated pesticide solution, containing 0.5-50 mass/vol.% one or more water insoluble pesticides and lignin in mass ratio lignin/pesticide of 1:10-1:1, dissolved in polar solvent mixable with water in amount to adjust total volume to 100 %. Dispersed in water concentrated pesticide solution is applied onto pests or locus thereof.

EFFECT: storage stable products.

9 cl, 7 tbl, 2 ex

FIELD: organic chemistry, pesticides.

SUBSTANCE: invention relates to concentrated pesticide solution, containing 0.5-50 mass/vol.% one or more water insoluble pesticides and lignin in mass ratio lignin/pesticide of 1:10-1:1, dissolved in polar solvent mixable with water in amount to adjust total volume to 100 %. Dispersed in water concentrated pesticide solution is applied onto pests or locus thereof.

EFFECT: storage stable products.

9 cl, 7 tbl, 2 ex

FIELD: herbicidal composition.

SUBSTANCE: invention relates to herbicidal composition in form of emulsifying concentrate containing (mass %): 2-methoxy-3,6-dichlorobenzoic acid 55-74; substituted sulfonylurea 0.5-2.5; surfactant 10-35; primary, secondary or tertiary amine 1-30; and balance: solvent.

EFFECT: herbicidal preparation with increased dispersity, improved emulsion stability and increased herbicidal activity.

3 cl, 2 tbl, 20 ex

Up!