Derivatives triazolopyrimidine, the retrieval method, the fungicidal composition, method of combating fungi

 

(57) Abstract:

Derivatives triazolopyrimidine General formula I, where R1possibly substituted alkyl, cycloalkyl or bicycloalkyl; R2is a hydrogen atom; R3- 3 - 4-membered ring containing one S atom of the heterocycle; R4is a halogen atom, is produced by interaction of the compounds of formula II in which Hal is chlorine or bromine, with a compound of the formula HNR1R2obtaining the compounds of formula I in which R4- chlorine atom or bromine, and optionally the reaction of the compounds I with a fluorinating agent to obtain compounds I in which R4the fluorine atom. The compounds of formula I exhibit fungicidal activity, especially against fungi from the class of records of Ascomycetes, such as Venturia inaequalis, Botrytis cineria and Alternaria solani. 5 S. and 6 C.p. f-crystals, 2 PL.

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This invention relates to certain derivatives of triazolopyrimidine, method of their preparation, compositions containing such compounds and their use as fungicides.

European application N 92204097.7, are simultaneously considered discloses compounds of General formula

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in which R1represents a possibly substituted alkyl, alkenyl, alkadienes, the CEC of the CP;

R1and R2together with the nitrogen atom between them represents a possibly substituted heterocyclic residue;

R3represents a possibly substituted aryl group;

R4represents a hydrogen atom, halogen atom or the group-NR5R6where R5is a hydrogen atom or an amino, alkyl, cycloalkyl or bicycloalkyl, group, and R6is a hydrogen atom or altergroup.

These compounds exhibit fungicidal activity, especially against fungi from the class of records of Ascomycetes, such as Venturia inaequalis, Botrytis cinerea u Alternaria solani.

Currently, it is found that some cycloalkyl and heterocyclic analogs of compounds of the formula A also exhibit fungicidal activity.

According to the invention provides compounds of formula

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in which R1represents a possibly substituted alkyl, alkenyl, alkadienes, cycloalkyl, bicycloalkyl or heterocyclyl;

R2represents a hydrogen atom or accelgroup, or R1and R2together with the nitrogen atom between them represents a possibly substituted heterocyclic residue;

R3represents a possibly substituted cycloalkyl or hetero is or amino, alkyl, cycloalkyl or bicycloalkyl and R6is a hydrogen atom or altergroup.

If compounds of this invention contains alkyl, alkenyl, quinil or alkadienes substituents, these substituents may be linear or branched and may contain up to 12, mainly to 6, and especially up to 4 carbon atoms. Cycloalkyl group may contain from 3 to 8, mostly 3 to 6 carbon atoms. Bicycloalkyl group may contain from 4 to 12, mostly 4 to 8 carbon atoms. The aryl group may be any aromatic hydrocarbon group, especially phenyl or naftilos group. Heterocyclic ring may be either saturated or unsaturated system of rings containing at least one heteroatom, preferably 3 - to 6-membered ring and a 5 - and 6-membered ring is particularly preferred. The most preferred nitrogen-, oxygen-, sulfur-containing heterocycles, such as pyridinyl, pyrimidinyl, pyrrolidinyl, furyl, pyranyl, morpholinyl, thienyl.

If any of the above substituents is indicated as possibly substituted, the substitute who may be present, can be one or more of the substituents typically used when creating a PE is you want to make, persistence, penetration or other properties. Specific examples of such substituents are, for example, halogen atoms, nitro, cyano, thiocyano, hydroxyl, alkyl, halogenated, cyanate, alkoxyl, halogenoalkanes, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulfonyl, alkylsulfonyl, carbarnoyl, alkylamino, phenyl, benzyl, benzyloxy, heterocyclyl, especially furyl, cycloalkyl, especially cyclopropyl. Usually can be 0 - 3 substituent. If any of the above substituents contains or represents aryl or cycloalkyl part, aryl or cycloalkyl part may itself be substituted by one or more halogen atoms, nitro, cyano, alkyl, halogenation, alkoxyl or halogenation. In the case of groups of cycloalkyl and heterocyclyl possible substituents include groups, with two intermediate carbon atom of cycloalkyl or heterocyclyl form a saturated or unsaturated hydrocarbon ring. In other words, a saturated or unsaturated hydrocarbon ring may be skondensirovannye with cycloalkyl or heterocyclyl group.

Preferably C3-8cycloalkyl or C4-8bicycloalkyl or 3 - to 6-membered heterocyclic ring, each group or ring may be substituted by one or more substituents selected from a halogen atom, nitro, cyano, hydroxyl, C1-4alkyl, C1-4halogenated, C1-4alkoxy, C1-4halogenoalkanes, amino, C1-4alkylamino, di-C1-4alkylamino, formyl, C1-4alkoxycarbonyl, carboxyl, phenyl, C1-4halogenosilanes, di-C1-4alkoxyphenyl, furyl, dihalogen-C3-6cycloalkyl or, in the case where R1represents a C3-8cycloalkyl group or a 3 - to 6-membered heterocyclic ring, possibly condensed in anthopology with the benzene ring.

More preferably, R1represents a C1-12alkyl, C2-6alkenyl, C2-4quinil, C4-8alkadienes, C3-8cycloalkyl, C4-8bicycloalkyl or 3-to 6-membered nitrogen-containing heterocyclic ring, which may include up to three substituents selected from halogen atoms, especially chlorine, hydroxyl, C1-4alkyl, especially methyl, C1-4halogenated, especially methoxyethyl, C1-4halogenations, especially triptoreline, phenyl, C1-41represents a C3-8cycloalkyl group or a 3 - to 6-membered heterocyclic ring, it is possible condensation with the benzene ring in anthopology.

Preferably R2represents a hydrogen atom or a C1-4altergroup.

It is also preferred that R3represents a C3-8cycloalkyl or 3 - to 6-membered heterocyclic ring, each group or ring may be substituted by one or more substituents selected from halogen atoms, nitro, cyano, hydroxyl, C1-4alkyl, C1-4halogenated, C1-4alkoxy, C1-4halogenations, amino, C1-4alkylamino, di-C1-4alkylamino, formyl, C1-4alkoxycarbonyl, carboxyl, phenyl, phenoxy and benzyloxy.

More preferably R3represents a C3-6cycloalkyl or 5 - to 6-membered heterocyclic ring, each group or ring may include up to three substituents selected from halogen atoms, C1-4alkyl, C1-4halogenated, C1-4alkoxy and C1-4halogenaryloxy.

Preferably R4represents a hydrogen atom or halogen atom, or a group - NR5R6where R4-8
bicycloalkyl and R6represents a hydrogen atom or a C1-4alkyl, especially methylgroup.

Especially preferred are the compounds of formula I in which R1represents propyl, cyclopentyl, bicycloheptane; R2is a hydrogen atom; R3- thienyl group; R4the chlorine atom.

The present invention also provides a method for producing compounds of formula I, above, which includes: (a) the reaction of compounds of General formula

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in which R3as presented above, and HaI - chlorine or bromine, with a compound of General formula

HNR1R2III

in which R1and R2as described above,

with the formation of the compounds of formula I in which R4represents a chlorine atom or bromine; (b) if required, the reaction of the compounds of formula I obtained by the method (a), with a fluorinating agent to form a compound of formula I, in which R4represents a fluorine atom; (c) if required, the reaction of the compound of the formula obtained by method (a) with a reducing agent to form a compound of formula I, in which R4represents the atom hydrogens; (d) if required, the reaction of the compounds of formula I, obtained cisano above,

before the formation of the compounds of formula I in which R4represents - NR5R6; (e) if required, the reaction of the compounds of formula I obtained by the method (d), in which R5and R6both represent a hydrogen atom, diiodomethane in the presence diastereomer agent before the formation of the compounds of formula I in which R4is an atom of iodine.

Method (a) is generally performed in the presence of a solvent. Suitable solvents include ethers, such as dioxane, diethyl ether, especially tetrahydrofuran, hydrohalogenation hydrocarbons, such as dichloromethane and toluene. The reaction well is performed at temperatures in the range from 0oC to 70oC, the preferred reaction temperature is from 10oC to 35oC. it is Also preferred that the reaction is carried out in the presence of a base. Suitable bases are tertiary amines, such as triethylamine, and inorganic bases such as potassium carbonate and sodium carbonate. Or they can serve as an excess of the compounds of formula III.

Method (b) it is convenient to perform in the presence of a solvent. Suitable solvents are sulfonal, dimethylformamide mixture of acetonitrile and crown ether.El to use toluene, to achieve degradation of the fluorinating agent. The reaction is usually carried out at a temperature in the range from room temperature (about 15oC) to the boiling temperature of the reaction mixture, the preferred reaction temperature is from 40oC to the boiling temperature of the reaction mixture. Suitable fluorinating agent are fluorides of alkali metals, especially potassium fluoride, and fluoride antimony.

The reducing agent at the stage (C) is usually catalytically hydrogenating reagent, it is the hydrogen that is used at an elevated pressure in the presence of a catalyst. Preferably the catalyst is palladium on carbon. It is also preferred that the method is carried out in the presence of a base. Suitable bases include tertiary amines, such as triethylamine, and inorganic bases such as sodium carbonate or, especially, sodium hydroxide. This stage can also usually be carried out in the presence of a solvent. Suitable solvents are alcohols, such as methanol. The reaction is usually performed at a temperature in the range from 0oC to 70oC, the preferred reaction temperature is from 10oC to 35oC.

Method (d) is usually performed in the presence of a solvent. Pirnie hydrocarbons, such as dichloromethane, and especially toluene. The reaction is usually conducted at a temperature in the range of 20oC to the boiling temperature of the reaction mixture, the preferred reaction temperature is from 40oC to the boiling temperature of the reaction mixture. It is preferable that the reaction is performed in the presence of a base. Suitable bases are tertiary amines, such as triethylamine, and inorganic bases such as potassium carbonate or sodium carbonate. Or as the base can be used an excess of the compounds of formula IV.

When R1represents the same Deputy that R5and R2represents the same Deputy that R6in the final compound of formula I, the compound of formula III is the same as the compound of the formula IV and stage (a) and (d) can therefore be performed in one stage using double the amount of amine of the formula III/IV.

Diastereomer agent used in stage (e), can be any alkilany ester of nitrous acid is particularly preferred isopentenyl. If you are using alkilany ester of nitrous acid, it can serve as a co-solvent and diiodomethane. The reaction is usually performed at temperatuere formula II can be obtained by the reaction of compounds of General formula

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in which R3above,

with glorieuses or brainwashin agent such as phosphorus oxychloride or bromacil phosphorus.

The compounds of formula V can be obtained by the reaction of 3-amino-1,2,4-triazole with the corresponding ester of malonic acid under alkaline conditions in accordance with the method of J. Makisumi, Chem. Pharm. Bull., 9, 801 (1961).

The compounds of formula II and IV are known compounds and can be obtained analogously to known methods.

It was found that compounds of General formula I possess fungicidal activity. Accordingly, the invention also provides fungicidal compositions which comprise a carrier and as active ingredient a compound of the formula I, which is described above. A method of obtaining such compositions also available, the method comprises introducing the compounds of formula I, described above, with at least one carrier. Such compositions can include one combination or mixture of various compounds of the present invention.

The compounds corresponding to the invention mainly contain from 0.5 to 95 wt.% the active ingredient.

The carrier in the compositions according to the invention, is any N, soil or for convenient storage, transportation and handling. The carriers may be solid or liquid materials, including those in the ordinary gaseous state, but which sigalda to liquid, and any media that is normally used for retseptoriani fungsinya drugs, can be used.

Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicates such as diatomaceous earth; magnesium silicates, such as talc; magnesium silicates, for example attapulgite and vermiculite; aluminum silicates, such as kaolin, montmorillonite and micas; calcium carbonate; calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxide and synthetic calcium silicates or aluminum; elements, for example carbon and sulphur; natural and synthetic resins, such as resin coumarone, polymers and copolymers based on polyvinyl chloride and styrene; solid polihlorvinila; bitumen; waxes, for example beeswax, paraffin wax chlorinated mineral waxes; and solid fertilizers, for example superphosphates.

Suitable liquid carriers are water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, metriso is xylene; fractions of oil, such as kerosene and light mineral oils; chlorinated hydrocarbons, for example, chetyrehhloristy carbon, pentachloroaniline and trichloroethane. Often suitable mixtures of different liquid media.

Antifungal drugs are often recaptured and transported in a concentrated form, which is further diluted immediately before use. The presence of small amounts of surfactants improves the dilution process. Thus it is preferable that at least one carrier in the drug corresponding to the invention, was surface-active substance. For example, the preparation may contain at least two carriers, at least one of which is a surface-active substance.

Surfactant may be an emulsifying agent, dispersing agent or wetting agent; it can be non-ionic and ionic. Examples of suitable surfactants are the salts of sodium and calcium polyacrylate and ligninsulfonate acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylenoxide them with ethylenoxide and/or propylene oxide; condensation products of fatty alcohols or alkyl phenols, for example p-op or p-ochiltree, with ethylene oxide and/or propylene oxide; sulfates or sulfonates of these condensation products, salts of alkaline and alkaline earth metals, predominantly sodium salts of sulfuric esters of sulfonic acids containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, (secondary alkyl) sodium sulfate, sodium salt from sulphonated castor oil and alkylarylsulfonate sodium, such as dodecylbenzenesulfonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.

The preparations of the invention can, for example, receptorrelated as wettable powders, dusty, granules, solutions, mulgirigala concentrates, emulsions, suspension concentrates and aerosols. Wettable powders usually contain 25, 50 or 75 wt.% the active ingredient and usually include, in addition to solid inert carrier 3 -10 wt.% dispersing agent and, if necessary, 0 -10 wt.% stabilizer(s) and/or other additives such as a wetting agent or a binding agent. Dusty usually recaptured as concentrate dust with a composition similar to the composition of smack to obtain a composition, usually containing 0.5 -10 wt.% the active ingredient. Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676-0.152 mm), they can be obtained by sintering or application. Typically, the granules will contain 0.5 -75% of the active ingredient and 0 to 10% of additives such as stabilizers, surfactants, slow release modifiers and binding agents. The so-called "dry flowable powders are composed of granules of relatively small size, having a relatively high concentration of the active ingredient. Mulgirigala concentrates usually contain, in addition to the solvent, if necessary, co-solvent, 1 to 50 wt%./about. the active ingredient, 2 to 20% wt./about. emulsifying agent and 0 to 20% of other additives such as stabilizers, wetting agents and corrosion inhibitors. Suspension concentrates are usually prepared to obtain stable, asedimentary fluid product, they usually contain 10 to 75% of active ingredient, from 0.5 to 15 wt.% dispersing agent, 0.1 to -10 wt.% suspendida agents such as protective colloids and thixotropic agents, 0-10% weight of other additives, such as antifoaming agents, corrosion inhibitors, stabilizers, wetting agents and svetousileniya solids or inorganic salts may be present in the specimen dissolved, to help protect them from sedimentation or as antifreeze agents for water.

Aqueous dispersions and emulsions, for example compositions obtained by diluting wettable powders or concentrates of the invention with water, also belong to the scope of the invention. The above emulsion may be of the type water-in-oil or oil-in-water and can be "mayonesa"-like consistency.

The preparations of the invention may also contain other ingredients, for example other compounds with herbicide, insecticide or fungicide properties.

Of particular interest to increase the duration of the protective effect of the compounds of this invention is the use of media that will provide a slow release of antifungal compounds in the environment of plants that protect. Such preparative forms with slow release of the active substance may for example be placed in the soil between the roots of the vine these forms may include adhesive components, allowing you to attach them directly to the tool of the vine.

The invention furthermore provides the use as fungicides compounds of General formula s with mushrooms in their habitats processing of these places, which can be for example plants undergoing or have already been subjected to fungal attack, seeds of such plants or the medium in which such plants are growing or have grown.

The present invention is widely applicable for the protection of various crops from the effects of mushrooms. For crops that can be protected by these drugs include the vine, cereals such as wheat and barley, apples and tomatoes. The duration of protection is usually dependent on the selected individual compounds, a variety of external factors, such as climate change, whose effects are usually reduced using a suitable form of application. Further, the invention is illustrated by the following examples.

Example 1

Getting 5 - chloro-6-Tien-3-yl-7-cyclopentylamine-1,2,4-triazolo[1,5-a] pyrimidine

(R1=cyclopentyl; R2=H; R3=Tien-3-yl; R4=Cl)

To 5,7-dichloro-6-Tien-3-yl-1,2,4-triazolo[1,5-a]pyrimidine (0.54 g, of 0.002 mol) in tetrahydrofuran (20 ml) was added a mixture of cyclopentylamine (0.2 g 0,002 mol), tetrahydrofuran (2 ml) and triethylamine (0.25 g, 0.002 mol), stirred 1 hour, then drove the solvent in vacuo, the residue was treated with ethyl acetate and water (50 ml each). The organic layer ottavia on silica gel using as eluent a mixture of ethyl acetate: petroleum ether (8:2) (300 ml) and was obtained 0.45 g of 5-chloro-6-Tien-3-yl-7-cyclopentylamine-1,2,4-triazolo[1,5-a] pyrimidine as colorless crystals, so pl. 78oC. Yield: 71% of theoretical.

Example 2 and 3

Using the method described in example 1 was then obtained compounds are shown in table 1. In this table, the compounds shown by formula 1.

Example 4.

The fungicidal activity of the compounds of the invention was studied using the following tests.

(a) Anticorrelation activity against downy mildew of grapevine (Piasmopara viticola; PVA)

Test anticorrelation activity includes direct spraying of the leaves. The bottom surface of the sheet of grape plants (varieties Cabernet Sauvignon), approximately 8 cm tall inoculant water suspension containing 5104zoosporangia/ml Inoculated plants are incubated 24 hours at 21oC in cells with high humidity, then 24 hours in the greenhouse at 20oC and 40% relative humidity. Infected leaves on the lower surface was sprayed with a solution of test compound in water/acetone (1: 1) containing 0.04% of "TWEEN 20" (trade name of a surface active substance, -polyoxyethylene ether sorbitan). Plants opryskivatel using a sprayer with 2 air spray nozzles. The concentration of C20oC and 40% relative humidity for 96 hours and then transferred to a chamber with high humidity for 24 hours for induction of sporulation. The assessment is conducted by the percentage of the surface of the sheet, which is sporulation compared to the same surface of the control.

(b) Direct protective activity against late blight of tomato (Phytophthora infestans; PIP)

Test direct protective action includes spraying the leaves. Tomato plants with two expanded leaves (sort of "First in the field" are sprayed with the test compound at a dose of 600 parts 1 million in the solution prepared by the method (a). After drying, the plants are kept for 24 hours in the greenhouse at 20oC and 40% relative humidity. The upper surface of the sheet inoculant water suspension containing 2105zoosporangia/ml Inoculated plants left for 24 hours at 18oC in cells with high humidity and then for 5 days in growth chambers under 15oC and 80% relative humidity with a 14 hour light day. The evaluation is made by the percentage of area affected sheet in comparison with the same value in the control.

(c) Activity against early rot of tomato (Alternaria solani, As).

The test is carried out using a leaf spray. Seedlings , million, prepared as described in method (a). Plants dried and left for 24 hours in the greenhouse at 20oC and 40% relative humidity, then inoculant the upper surface of the sheet with an aqueous suspension of conidia of A. Solani containing 1104conidia/ml, incubated in a chamber with high humidity at 21oC 4 days and evaluated by the percentage of the surface of the affected sheet in comparison with this value for the control.

(d) a Direct protective effect against gray mold of beans (Botrytis cinerea; BCB)

Test direct protective action carried out using a leaf spray. Plant beans (sort Sutton) with two pairs of leaves are sprayed with a solution of the test compounds at a dose of 600 parts per 1 million, prepared as described in method (a), dried, placed for 24 hours in a glasshouse at 20oC and 40% relative humidity, then the upper surface of the sheet inoculant water suspension containing 1106conidia/ml of the Plant is left for 4 days at 22oC in a chamber with high humidity. The evaluation is made by the percentage of the surface of the affected sheet in comparison with this value in the control.

(e) Activity against Glazkova blotch of wheat in vitro (Pseudocercosporella herpotrichoides; PHI)

This test determines the activity is Aut or suspended in acetone and added to a 4 ml aliquot of potato dextrose broth, half fortress 25-aceitou a Petri dish to obtain a final concentration of 30 parts per million the tested compounds and 0.825% acetone. The inoculum of the fungus consists of miralievich fragments of P. herpotrichoides. grown on potato dextrose broth, half fortress in shake flask and added to the broth to obtain 5104miralievich fragments/ml of broth. Petri dishes are incubated at 20oC for 10 days to assess michelago growth.

(f) Activity against Rhizoctonia in vitro (Rhozoctonia Solani; PSI)

The test determines the activity in vitro of the compounds against Rhizoctonia solani, which causes stem and root rot. The test compound dissolved or suspended in acetone and added to a 4 ml aliquot of potato dextrose broth, half fortress 25-aceitou a Petri dish to obtain a final concentration of 30 parts per million connections and 0.825% acetone. The inoculum of the fungus consists of fragments of mycelium of R. Solani grown in dextrose broth, half fortress in shake flask and added to the broth to obtain 5104miralievich fragments/ml of broth. Petri dishes are incubated at 20oC for 10 days to assess michelago growth.

(g) Activity against scab of apples in vitro (Venturia inaequalis; (VII)

This test determines the activity in vitro of the compounds against Ve in 4 ml aliquot of potato dextrose broth, half fortress, a 25-mesh Petri dish to obtain a final concentration of 30 parts per million and 0.825% acetone. The inoculum of the fungus consists of miralievich fragments and spores. V. inaequalis grown on malt agar and added to the broth to obtain 5104propagules/ml of broth. Petri dishes are incubated at 20oC for 10 days to assess the growth of the mycelium.

The degree of suppression of the disease in all of the above tests is expressed as a score when compared to untreated control or control treated only with solvent without a connection, in accordance with criteria:

0 = less than 50% suppression of the disease

1 = 50-80% suppression of disease

2 = more than 80% suppression of disease

The results of these tests are placed in table 2.

Examples of compositions

Example 5 (emulsifiable concentrate (EC))

Active ingredient: 30% (V/o)

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(Example 1)

The emulsifier(s) Atlox4856 B/Atlox4858 B1)(the mixture containing alkylarylsulfonate calcium, ethoxylates of fatty alcohols and boiling aromatic compounds/mixtures containing alkylarylsulfonate calcium, ethoxylates of fatty alcohols and boiling aromatic compounds) and 5% (V/o)

The solvent ShellsolA2)(a mixture of C9-C10-aromatic hydrocarbons) - Dispersant SopropholFL3)(polyoxyethylene polyaryl femalefirst, salt with the amine) - 3% (V/o)

Rhodorsil antifoam4223)(non-ionic aqueous emulsion of polydimethylsiloxane) to 0.2% (V/o)

The amendment KelzanS4)(xanthan gum) to 0.2% (V/o)

Antifreeze Propylene glycol - 5% (V/o)

Biocidal agent Proxel5)(aqueous solution of dipropyleneglycol containing 20% 1,2-benfotiamin-3-one) and 0.1% (V/o)

Water Up to 1000 ml

Example 7 (Wettable powder (SP))

Active ingredient: 60% (in/in)

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(Example 1)

Wetting agent Atlox49951)(alkilany ether polyethylene) - 2% (in/in)

Dispersant WitcosperseD-606)(mixture of sodium salts of condensed naphthalenesulfonate and alkylarylsulfonates) - 3% (in/in)

Carrier/filler Kaolin - 35% (in/in)

Example 8 (water-dispersible granules (WG))

Active ingredient: 50% (V/C)

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(Example 1)

Dispersant/binder WitcosperseD-4508)(mixture of sodium salts of condensed naphthalenesulfonates acid and alkyl sulphonates) - 8% (in/in)

Wetting agent Morwet8)(the condensation products of formaldegidnym AgrimerATF7)(cross-linked homopolymer of N-vinyl-2-pyrrolidone) - 2% (in/in)

Carrier/filler Kaolin - 35% (in/in)

Example 9 (emulsifiable Concentrate (EC))

Active ingredient: 30% (V/o)

< / BR>
(Example 2)

The emulsifier(s) Atlox4856 B/Atlox4858 B1)(the mixture containing alkylarylsulfonate calcium, ethoxylates of fatty alcohols and boiling aromatic compounds/mixtures containing alkylarylsulfonate calcium, ethoxylates of fatty alcohols and boiling aromatic compounds) and 5% (V/o)

The solvent Shellsol2)(a mixture of C9-C10-aromatic hydrocarbons) - Up to 1000 ml

Example 10 (suspension Concentrate (SC))

Active ingredient: 50% (V/o)

< / BR>
(Example 2)

Dispersant SoprophorFL3)(polyoxyethylene polyaryl femalefirst, salt with the amine) - 3% (V/o)

Rhodorsil antifoam4223)(non-ionic aqueous emulsion of polydimethylsiloxane) to 0.2% (V/o)

The amendment KelzanS4)(xanthan gum) to 0.2% (V/o)

Antifreeze Propylene glycol - 5% (V/o)

Biocidal agent Proxel5)(aqueous solution of dipropyleneglycol containing 20% 1,2-Beni is t - 60% (in/in)

< / BR>
(Example 2)

Wetting agent Atlox49951)(alkilany ether polyethylene) - 2% (in/in)

Dispersant WitcosperseD-606)(mixture of sodium salts of condensed naphthalenesulfonate and alkylarylsulfonates) - 3% (in/in)

Carrier/filler Kaolin - 35% (in/in)

Example 12 (water dispersible granules (WG))

Active ingredient: 50% (V/C)

< / BR>
(Example 2)

Dispersant/binder WitcosperseD-4506)(mixture of sodium salts of condensed naphthalenesulfonate and alkyl sulphonates) - 8% (in/in)

Wetting agent MorwetTFW6)(the condensation product of formaldehyde) - 2% (in/in)

Rhodorsil antifoamEP 67033)(encapsulated silicone) - 1% (V/C)

Disintegrant AgrimerATF7)(crosslinked homopolymer of N-vinyl-2-pyrrolidone) - 2% (in/in)

Carrier/filler Kaolin - 35% (in/in)

1) the Product is on sale from ICI Surfactants

2) the Product is on sale from Deutsche Shell AG

3) the Product is on sale from Rhone-Poulenc

4) the Product is on sale from Kelco Co.

5) the Product is on sale from Zeneka

6) the Product is on sale from Witco

7) Product sales from International Speciality Products

1. Derivative triazolopyrimidine;

R2represents a hydrogen atom;

R3represents a 3 - or 4-membered ring containing one atom S heterocyclyl;

R4represents a halogen atom.

2. Connection on p. 1, in which R1represents a C1- C12-alkyl, C3- C8-cycloalkyl or C4- C8-bicycloalkyl.

3. The compound according to any one of the preceding paragraphs, in which R3is thienyl.

4. The compound according to any one of paragraphs.1 to 3, in which R1represents propyl, cyclopentyl or bicycloheptene, R2is a hydrogen atom, R3- tailgroup, R4represents a chlorine atom.

5. The method of obtaining the compounds of formula I, as defined in the PP.1 to 4, including (a) the reaction of compounds of General formula II

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where R3- as defined in the PP.1 to 4;

Hal represents chlorine or bromine,

with a compound of General formula III

HNR1R2< / BR>
where R1and R2- as defined in any of the preceding paragraphs,

obtaining the compounds of formula I in which R4represents a chlorine atom or bromine, and optionally (C) reaction of the obtained compound of formula I with a fluorinating agent with p is obom under item 5.

7. Fungicidal composition comprising a carrier and an active ingredient - derived triazolopyrimidine, characterized in that as the latter contains a compound of formula I under item 1 in the amount of 0.5 to 95 wt.%.

8. The composition according to p. 7, characterized in that the part of the carrier is a surface-active agent.

9. A method of combating fungi in the place of their habitat, which includes the processing of habitats derived triazolopyrimidine, characterized in that as the latter is used as a compound of formula I at the rate of deposition of 750 l/g of the composition containing 30 to 600 ppm compound under item 1.

10. The method according to p. 9, in which the habitat includes plants subjected or exposed to infestation by fungi.

11. Derivatives triazolopyrimidine on PP.1 to 4, showing fungicidal properties.

 

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,5,6]-6-amino-3-azabicyclo [3.1.0] gex-3-yl)- 6-fluoro-1-(2,4-differenl)-1,4 - dihydro-4-oxo-1,8 - naphthiridine-3-carboxylic and methanesulfonic acid and its preparation" target="_blank">

The invention relates to a new form of the anhydrous salt methanesulfonic acid and 7-([1,5,6]-6-amino-3-azabicyclo[3.1.0] Gex-3-yl)-6-fluoro-1-(2,4-differenl)- 1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid, to a method of use of the compounds in the treatment of bacterial infections in mammals, especially humans, and to pharmaceutical compositions useful for him

The invention relates to pyrazolopyrimidines General formula I and their pharmaceutically acceptable salts, where A is the group NR1R2or CR'1R'2R11, R1- H or C1-C6-alkyl, unsubstituted or substituted certain substituents, such as HE, F, CL and others, or C2-C6alkenyl; or C2-C6-quinil; R2-C1-C6-alkyl, unsubstituted or substituted certain substituents, such as HE, C1-C6-alkoxy and others; or C2-C6alkenyl or2-C6-quinil, or furanyl; and (C1-C4-alkylene)phenyl which may be substituted by 1 to 3 substituents: CL, F, C1-C4-alkyl, and one Deputy:1-C6-alkoxy, CF3, NO2, NH2; or (C1-C4-alkylen) hetaryl where hetaryl - thienyl, possibly substituted by CL, benzothiazyl, pyridyl, chinoline, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, pyrrolyl, pyrrolidinyl, 1-benzylpiperidine, tetrahydropyranyl; or (C1-C4-alkylen)cyclopropyl; or NR1R2form hetaryl selected from the group consisting of pyrrolidyl, possibly substituted benzyl, pyrrolidinyl, possibly substituted by benzyl or HE, the IIR>-C6-alkyl; R3is hydrogen, C1-C6-alkyl, O-(C1-C6alkyl), S(C1-C4- alkyl); R4- C1-C6- alkyl, or S(O)n(C1-C6)-alkyl, where n= 0-2, R5- 2,4,6-substituted phenyl CL, C1-C6-alkyl, CF3; R11-N., HE, or COO- (C1-C2alkyl), provided that the group CR'1R'2R11not an alkyl straight chain; and when R3is N, then R4isn't C1-C6the alkyl

The invention relates to pharmaceutical compositions for the treatment of inflammatory diseases, for example asthma, arthritis and allergies; fear; depression; fatigue syndrome; headache; pain; cancer; irritable bowel syndrome, including Crohn's disease, mucous colitis and symptoms of irritation of the colon; deregulation of the immune system; infections caused by human immunodeficiency virus (HIV); neurovirology diseases, such as Alzheimer's disease; gastrointestinal diseases; disorders of appetite, such as anorexia nervous system; stress caused by bleeding; symptoms of drug and alcohol withdrawal symptoms; addiction to the excessive use of drugs; stress-induced psychotic States and problems of fertilization, containing the above compound of formula I is effective for the treatment of these diseases the number and pharmaceutically acceptable carrier

The invention relates to organic chemistry, specifically to a method for producing 5-hydroxy-6-methyluracil, showing immunotropic activity permitted for medical use and industrial production, and can also be used in the treatment of immune disorders of different Genesis

The invention relates to new derivatives of salicylic acid f-ly Gets-NR-SO2-Ph1A Ph2(COOH)(OH), (I), where Het represents (R1, R2, R3-Het1That gets1represents a cyclic systemin which the free valence is associated with a group NR; X is a group: a) -O-CH=CH-, -CH=CH-O-, -CH= CH-S - or b) -CH=CH-CH=CH-, -CH=CH-CH=N-, -CH=N-CH=CH-, -CH=CH-N=CH-, -N= CH-CH= CH-; R1, R2and R3are substituents at the carbon atom in Het and represent hydrogen, C1-C6- alkyl, halogen, hydroxy - or benzyloxy; R is hydrogen or C1-C6- alkyl; Ph1- phenylene, Ph2is phenyl which may be substituted with halogen, lower alkyl or benzyloxypropionic, provided that the carboxy - and hydroxy-group are in the ortho-position to each other; And a represents - CC-, -CH=CH-, -CH2-CH2-, -CO-CH=CH-, -CH=CH-CO-

The invention relates to new derivatives of salicylic acid f-ly Gets-NR-SO2-Ph1A Ph2(COOH)(OH), (I), where Het represents (R1, R2, R3-Het1That gets1represents a cyclic systemin which the free valence is associated with a group NR; X is a group: a) -O-CH=CH-, -CH=CH-O-, -CH= CH-S - or b) -CH=CH-CH=CH-, -CH=CH-CH=N-, -CH=N-CH=CH-, -CH=CH-N=CH-, -N= CH-CH= CH-; R1, R2and R3are substituents at the carbon atom in Het and represent hydrogen, C1-C6- alkyl, halogen, hydroxy - or benzyloxy; R is hydrogen or C1-C6- alkyl; Ph1- phenylene, Ph2is phenyl which may be substituted with halogen, lower alkyl or benzyloxypropionic, provided that the carboxy - and hydroxy-group are in the ortho-position to each other; And a represents - CC-, -CH=CH-, -CH2-CH2-, -CO-CH=CH-, -CH=CH-CO-

The invention relates to pyrazolopyrimidines General formula I and their pharmaceutically acceptable salts, where A is the group NR1R2or CR'1R'2R11, R1- H or C1-C6-alkyl, unsubstituted or substituted certain substituents, such as HE, F, CL and others, or C2-C6alkenyl; or C2-C6-quinil; R2-C1-C6-alkyl, unsubstituted or substituted certain substituents, such as HE, C1-C6-alkoxy and others; or C2-C6alkenyl or2-C6-quinil, or furanyl; and (C1-C4-alkylene)phenyl which may be substituted by 1 to 3 substituents: CL, F, C1-C4-alkyl, and one Deputy:1-C6-alkoxy, CF3, NO2, NH2; or (C1-C4-alkylen) hetaryl where hetaryl - thienyl, possibly substituted by CL, benzothiazyl, pyridyl, chinoline, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, pyrrolyl, pyrrolidinyl, 1-benzylpiperidine, tetrahydropyranyl; or (C1-C4-alkylen)cyclopropyl; or NR1R2form hetaryl selected from the group consisting of pyrrolidyl, possibly substituted benzyl, pyrrolidinyl, possibly substituted by benzyl or HE, the IIR>-C6-alkyl; R3is hydrogen, C1-C6-alkyl, O-(C1-C6alkyl), S(C1-C4- alkyl); R4- C1-C6- alkyl, or S(O)n(C1-C6)-alkyl, where n= 0-2, R5- 2,4,6-substituted phenyl CL, C1-C6-alkyl, CF3; R11-N., HE, or COO- (C1-C2alkyl), provided that the group CR'1R'2R11not an alkyl straight chain; and when R3is N, then R4isn't C1-C6the alkyl

The invention relates to pharmaceutical compositions for the treatment of inflammatory diseases, for example asthma, arthritis and allergies; fear; depression; fatigue syndrome; headache; pain; cancer; irritable bowel syndrome, including Crohn's disease, mucous colitis and symptoms of irritation of the colon; deregulation of the immune system; infections caused by human immunodeficiency virus (HIV); neurovirology diseases, such as Alzheimer's disease; gastrointestinal diseases; disorders of appetite, such as anorexia nervous system; stress caused by bleeding; symptoms of drug and alcohol withdrawal symptoms; addiction to the excessive use of drugs; stress-induced psychotic States and problems of fertilization, containing the above compound of formula I is effective for the treatment of these diseases the number and pharmaceutically acceptable carrier

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to an intermediate compound, i. e. tert.-butyl-(E)-(6-{2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidine-5-yl}-(4R,6S)-2,2-dimethyl[1,3]dioxane-4-yl]acetate that can be used in synthesis of compound of the formula (IV)

eliciting inhibitory effect on activity of HMG-CoA-reductase and, therefore, can be used for preparing pharmaceutical agents for treatment, for example, hypercholesterolemia, hyperproteinemia and atherosclerosis. Also, invention relates to a method for preparing indicated intermediate compound by reaction of the new parent compound - diphenyl-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidine-5-ylmethyl]phosphine oxide with tert.-butyl-2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxane-4-yl]acetate in the presence of a strong base in simple ether or aromatic solvents or their mixtures at temperature in the range from -200C to -900C. Also, invention relates to a method for preparing of compound of the formula (IV) wherein R1 means hydrogen atom or pharmaceutically acceptable cation and to a method for preparing intermediate compounds of the formula (VI):

wherein each P1 and P2 represents independently (C1-C4)-alkyl or group:

and wherein P3 represents (C1-C8)-alkyl. Applying new intermediate compounds and proposed methods provide enhancing quality and yield of compounds.

EFFECT: improved preparing methods.

9 cl, 1 tbl, 8 ex

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