The method of obtaining substituted falicov or heterocyclic falicov

 

(57) Abstract:

Usage: in the chemistry of heterocyclic substances, in particular in a method of producing substituted phthalimido or heterocyclic phthalimido. The inventive product is substituted phthalimide or heterocyclic phthalimide total f-crystals I. reaction Conditions: synthesis are the reaction of the compound f-crystals II with compound f-ly III connection f-IV crystals, which then either hydrolyzing, or treated with an amine or an alcoholate of an alkali metal or etherification or halogenous or carry out ring-opening of the connection f-crystals IV. Formulas I, II, III, IV (see drawing). 1 Il. 7 table.

The invention relates to organic synthesis and concerns a method for obtaining substituted falicov and heterocyclic falicov General formula

(I) where ring a is selected from the group comprising residues:

a) phenyl,

b) pyridyl,

b) five-membered heteroaromatic ring containing oxygen, sulfur or nitrogen as a heteroatom;

R cyano, formyl, ketonuria group, carboxyl group, which may be in the form of the free acid, ester or salt, carnemolla group or mono - or disubstituted carnemolla group or ring

1-8-alkyl, C2-8-alkenyl,2-8-quinil,1-8-alkoxy, C2-8-alkenylamine,2-8-alkyloxy,1-8-alkylsulfonate, each of which may be substituted by 1 to 6 halogen atoms and conjugated WITH1-8-alkoxyl,2-8-acyl, phenyl WITH1-8-alkoxyl, phenylthio, each of which can be substituted one or three halogen atoms;

Y1and Y2taken together with the adjacent carbon atoms form a group-C(O)-O-CH2;

each of W1, W2, W3, W4and W5independently is CH, CR3or N;

Z is a bridge consisting of elements selected from the group of methylene, substituted methylene, -C(O)-;

R1and R2each independently hydrogen, halogen, C1-8-alkyl, C1-8-alkoxy, C2-8-alkenylamine,2-8-alkyloxy, each of which may be substituted by 1 to 6 halogen atoms, 5 - or 6-membered heterocycle-C1-8-alkoxy, phenyloxy or phenyl-C1-8-alkoxy, each of which may be substituted by 1-3 substituents selected from halogen or1-8-alkyl; R2WITH1-8-alkyl, phenyl-C1-8-alkoxy or phenyl;

X and Y each independently hydrogen, hydroxyl, halogen, CA1-8-alkylthio, phenyloxy, phenyl S, each of which may be substituted by 1-3 halogen atoms, or together they predstavljaet,S,NH,NOR12CR13R14;

or X and R together may form a bridge having the formula-C(O)-O - or-C(O)-NR2where the carbonyl is attached to A; with the proviso that when R carboxyl in free ether or salt and X and Y together javlautsa, one of the rings a and b contains a heteroatom.

The method according to the invention differs in that

a) when X and R are combined with the formation of the bridging group as defined above, and Y is hydrogen, cyano or aaltio carry out the reaction of the compound of the formula

(II) where the ring A, Y1, Y2and Y3defined above; Y is hydrogen, cyano or aaltio; Z1oxygen, sulfur or NR2where R2defined above, with a compound of the formula

R (III) where W1, W2, W3, W4and R1defined above; R21methylsulphonyl or halogen, to obtain the corresponding compounds of the formula

(II)

b) process the compound of the formula I'where Y1cyano or arylsulfonyl; Z oxygen.

1) by hydrolysis to obtain the corresponding compound of formula I, where R1and X form a mos is inane formula I, where R is a possibly substituted carbamoyl group; X and Y together obrzut;

3) the group MOR22where M is alkali metal; R22hydrogen or C1-8-alkyl, to obtain the corresponding compound where R and X form a bridge; Y is hydroxyl or1-8-alkoxyl.

C) carry out the hydrolysis of the compounds of formula I'where Y1hydrogen; Z1, oxygen, and other characters such as defined above to obtain compounds of formula I in which R is carboxyl group, possibly in the form of a salt; X is hydrogen; Y is hydroxy;

g) open ring in the compound of the formula I'where Y1hydroxyl; Z1oxygen and other characters, such as defined above, to obtain compounds of formula I, where R is a carboxyl group, possibly in the form of a salt; X and Y together obrzut,

d) atrificial compound of formula I, where R is a carboxyl group, possibly in the form of a salt; X and Y0, and other characters such as defined above, to obtain the corresponding compounds of formula I, where R is a carboxyl group in the form of ether.

e) halogenous compound of the formula I'where Y1hydroxyl; Z1defined in paragraph (a), other characters mentioned above to obtain compounds of formula I, g is the I'where Z1oxygen; Y1halogen, and other symbols such as defined above, with a group of R2NH2and HOR group23where R2defined above; R23is1-8-alkyl, C2-8-acyl or aryl, to obtain the corresponding compounds where Z1NR2; Y1C1-8-alkoxy, aryloxy or2-8-acyloxy,

C) carry out the oxidation of the formula I'where Y1hydrogen; X1defined in paragraph (a), other characters mentioned above, to obtain the corresponding compounds in which Y1hydroxyl,

and) carry out the interaction of the compounds of formula I'where Z1oxygen; Y1hydrogen, other characters such as defined above, with a group of R7NH2where R7hydrogen, halogen; alkyl, alkenyl; quinil, alkoxy, alkenylacyl, alkyloxy, each of which in turn may be substituted by 1 to 6 halogen atoms and each of which can be attached to the adjacent nitrogen atom through alkyl; acyl; cycloalkyl, cycloalkenyl, heterocyclyl, heteroseksualci, heterocyclics, aryl, aralkyl, aryloxy, Alcoxy, each of which is substituted or may be substituted by 1-3 substituents selected from (1) halogen, 2) alkyl, and the go substituted by 1-6 halogen atoms, and 3) nitro, cyano, acyl, amino, substituted amino, aminosulfonyl, aminoalkyl or substituted aminoalkyl; amino, substituted amino, amido, substituted amido, aminosulfonyl, cyano - or nitro, for obtaining the compounds of formula I where R is monosubstituted carbarnoyl; X is hydrogen; Y is hydroxyl,

K) sulfonium, carbamoylethyl, acelerou or carboxilic the compounds of formula IIwhere Z1oxygen; Y1-hydroxyl and other characters such as defined above, to obtain the corresponding compounds of formula I, where R and X form-C(O)-O - bridge; Y carbamoylated,2-8-acyloxy or1-8-alkoxycarbonyl,

l) carry out the reaction of the compounds of formula I'where Z1oxygen; Y1halogen, and other symbols such as defined above, with a group of R7R8NH, where R7defined in paragraph (I); R8the same as defined for R7with obtaining the compounds of formula I in which R is twice substituted by carbamoyl; X and Y together represent 0;

and produce the compound obtained in which R is carboxyl or dicarboxylate group in free form or in the form of an ether, and a compound in which R carboxyl, in free form or in salt form.

Table.1 illustrates the conditions readem.

Compounds of formulas have a weed-killing activity, as observed in their application prior to the arrival or after emergence of the weeds or to the locus of the weeds.

The expression "herbicide" is used here to refer to the active ingredient or created the effect that modifies the growth of plants because of its properties regulating plant growth, or fetotoxicity properties so that plant growth is delayed or they are damaged sufficiently to destroy them.

The use of the compounds of formula I is carried out according to the usual procedure of weeds or their locus using herbicide effective amount of the compound is usually from 10 g to 10 kg per hectare.

Compounds according to the invention can be used to combat broadleaf or grass weeds before emergence, and after their occurrence. Compounds can also show selectivity towards various high-yielding crops and are suitable for combating weeds in cultivated plants, such as corn, cotton, wheat and soybeans.

The optimal number of the compounds of formula I can easily be determined by a specialist using ispy is to function effectively at higher concentrations, than regulating plant growth effect), treatment conditions, etc. In General satisfactory fetotoxicities effects get when the compound of the formula I are used in concentrations of 0.01 to 5.0 kg, more preferably 0.05 to 2.5 kg per hectare, for example 0,05-5,0 kg / ha, in particular 0.1 to 2.5 kg per hectare.

The compounds of formula I can be used with other broad spectrum herbicides on weeds, such as carbamates, thiocarbamates, chloracetamide, dinitroanilines, benzoic acid, glycerol esters, pyridazinone, procarbazine, orally and urea for broad-spectrum weed.

The compounds of formula I useful in the form of herbicide compositions in combination with acceptable in agriculture diluents. They may contain, in addition to the compounds of formula I as the active agent, other active agents, such as herbicides or connection with antidote, fungicidal, insecticidal or attract insect activity. They are used both in solid and in liquid form, for example in the form OnlineUsers powder or capable of emulsification concentrate, including traditional thinners. Such compositions can be obtained traditional what gradiently, such as surface-active substances.

Acceptable additives can be such additives, which are used in herbicide compositions to improve the effectiveness of the active ingredient and to reduce, for example, foaming, clumping and corrosion.

The term "diluent" means any liquid or solid substance, which is acceptable in agriculture, which can be added to the active component to make it more convenient or easily applicable form and with the required force activity. Such substances can be, for example, talc, kaolin, diatomaceous earth, xylene or water.

The terms "surfactant" means acceptable in agriculture substance that tells the emulsifying, dispersing, wetting, spreading, or other modifying surface properties. Examples of such substances are ligninsulfonate and valium. For example, compositions that are applied in spray form, such as dispersible in water concentrates or wettable powders, which can include surface-active substances, such as wetting and dispersing agents, for example condensation product formal 0.01 to 90 wt. active agent and 0-20 wt. acceptable in agriculture surfactant and active agent comprises any of at least one of the compounds of formula I, or of mixtures thereof with other active agents. Concentrated formula compositions contain about 2-90 wt. preferably, about 5-70 wt. the active agent. Ready () form of the composition can, for example, contain from 0.01 to 20 wt. the active agent.

The following are examples to illustrate the present invention. Temperature is given in degrees Celsius. The text uses the following abbreviations:

THF tetrahydrofuran;

LDA sitedisability;

CT room temperature;

DMF is dimethylformamide;

DDQ 2,3-dichloro-5,6-dicyanobenzoquinone;

NBS N-bromosuccinimide;

DMSO dimethyl sulfoxide;

MEK methyl ethyl ketone;

DMAP dimethylaminopyridine.

Individual alkyl substituents listed below in the following tables are the compounds in the n-isomeric form, unless you specify otherwise.

P R im e R 1. 7-Chloro-3-(4,6-dimethoxy-2-pyrimidinyl)phtalic (PL.2, compound 6).

7-Chlorophthalic 1.68 g (0.01 mol) is added to 100 ml of dry THF and the mixture is cooled to -70aboutC. Then The After that of 2.18 g (0.01 mol) of 2-methylsulphonyl-4,6-dimethoxypyridine-DIN in 50 ml added to this mixture, which is stirred for 4 h at (-75) (-70)aboutC. the Reaction mixture is neutralized 1.5 g NH4Cl in 5 ml of water, heat and concentrate on a rotary evaporators. The concentrate is shared between CH2Cl2and H2(Each 50 ml), separating the aqueous phase and treated with 30 ml of CH2Cl2. Connection CH2Cl2phases are washed with 30 ml of water, separated and concentrated. Concentrate flashamateur on silica gel using 80/20 hexane/ethyl acetate, 50/50 hexane/ethyl acetate (500 ml) and 80/20 acetone/methanol (500 ml): 30 fractions x 50 ml Target compound is obtained after recrystallization from hexane/CH2Cl2in the form of a white solid with a melting point 148-149aboutC.

P R I m m e R 2. 5-(4,6-Dimethoxy-2-pyrimidinyl)-furo[3,4,b]pyridine-7(5H)-on (PL.3, the connection 40).

A solution of 1.3 g (0,0096 mol) furo[3,4,b]pyridin-7(4H)-he in 50 ml of dry THF cooled to -75aboutAnd dropwise over 5 minutes add 8 ml (0,0192 mol) of 2.5 M LDA. The mixture is left to react for 1 h at -75aboutAnd dropwise within 10 min add 2.1 g (0,0096 mol) of 2-methylsulphonyl-4,6-dimethoxypyrimidine in 30 ml of dry THF. The mixture is left to warm to K. So add 1.6 ml of HCl and the THF is evaporated. The residue is dissolved in 75 ml of CHOptomega solids. This substance chromatographic on silicagel column using 50/50 hexane/ethyl acetate (500 ml), ethyl acetate (500 ml) and 80/20 acetone/methanol (1000 ml): 30 fractions. The crystalline residue (fraction 18-21) of the target product has a melting point of 167-168aboutC.

P R I m e R 3. 7-Chloro-3-methoxy-3-(4,6-dimethoxy-2-pyrimidinyl)-2-motility - ndol-1(3H)-he (PL.4, compound 54).

A mixture of 0.5 g of 7-chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidyl)phthalide, 30 ml of CCl4, 2 ml SOCl2and 4 drops of DMF are heated at 65aboutC for 1.5 h, cooled and the excess SOCl2and CCl4removed on a rotary evaporators. The residue is diluted with 20 ml of CH2Cl2and add to the mixture 5 ml of 40% aqueous methylamine and 10 ml of methanol with stirring for 0.5 hours the Mixture is placed in a rotary evaporators and the remainder divided between CH2Cl2and water of 50 ml each. The organic phase is concentrated and flashamateur on silica gel using 50/50 hexane/ethyl acetate (800 ml), ethyl acetate (500 ml) and 80/20 acetone/methanol (200 ml): 30 fractions x 50 ml Product (fractions 19-21) was obtained as a yellow rubbery substance.

P R I m e R 4. 7-Chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phtalic (PL.2, the connection 13).

P R I m e R 5. 7-Chloro-3-methoxy-3-(4,6-dimethoxy-2-pyrimidinyl)phtalic (PL. 2, the connection 30).

7-Chloro-3-cyano-3-(4,6-dimethoxy-2-PI-rimidine)phtalic (1 g) is dissolved in 20 ml of ethanol, the solution is cooled on ice and added dropwise 0.6 ml of sodium methoxide. After stirring for 10 min add 1 ml of sodium methoxide, stirring is continued for 10 min and then the mixture is cooled 2n. H2SO4. The methanol is removed on a rotary evaporators and the residue is divided between water and ethyl acetate. The organic phase is dried over sodium sulfate and concentrated. Flashmemory residue on silica gel using 25% ethyl acetate/hexane yields a white solid Mesnil)benzoate (table.4, compound 55);

b). 7-Chloro-3-chloro-(4,6-dimethoxy-2-pyrimidinyl)phtalic (PL. 2, the connection 21).

A mixture of 0.7 g of 7-chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 30 ml of CCl42 ml SOCl2and 4 drops of DMF is heated under reflux at 60aboutC for 1.5 h the Mixture was then cooled, the excess SOCl2and CCl4removed on a rotary evaporators. The residue is diluted with 20 ml of CH2Cl2and to this mixture with stirring, add 10 ml of methanol and 2 ml of diethylamine. After 2.5 h the mixture is placed in a rotary evaporators to remove excess CH2Cl2and methanol, the residue is divided between CH2Cl2(50 ml) and water (50 ml). The organic phase is separated, concentrated and rubbery residue flashamateur on silica gel using 80/20 hexane/ethyl acetate (500 ml), 60/40 hexane/ethyl acetate (500 ml): 20 fractions x 50 ml. Fractions 18-20 gave compound a), and fractions 11-16 connection b).

P R I m e R 7. 7-Chloro-3-cyano-3-(4,6-dimethoxy-2-pyrimidinyl)phtalic (PL.2, the connection 27).

7-Chloro-3-cyanophthalide (600 mg) is added to an ice slurry washed with hexane NaH (160 mg), 60% in DMF (20 ml). After 15 minutes add 710 mg of 2-methylsulphonyl-4,6-dimethoxypyrimidine. After stirring at room temperature trout and dried in a vacuum oven to obtain the specified product with so pl. 159-161aboutC.

P R I m e R 8. 7-Chloro-3,3-bis(4,6-dimethoxy-1,3,5-triazine-2-yl)phtalic (PL.2, compound 36).

7-Chlorthalid (1.48 g) was dissolved in 80 ml of THF. The solution is cooled to -70aboutWith and inject at -70aboutC for 3 min 1.5 M LDA in THF (6 ml). Stirring is continued for 15 min at -70aboutWith that added dropwise 1.54 g of 2-chloro-4,6-dimethoxy-1,3,5-triazine in 50 ml of THF and then the mixture is left to warm to -20aboutC. the Mixture is again cooled to -70aboutWith and add 1 ml of concentrated HCl in 10 ml of water. The mixture is stirred for 25 min and she is allowed to warm to K. So while THF is removed by evaporation. The remainder is divided between CH2Cl2and water (each 50 ml), the aqueous phase is extracted with an additional 30 ml of CH2Cl2. The combined organic phases are washed with 30 ml of water and concentrated to obtain a yellow rubbery substance. It flashamateur on silica gel using 60/40 hexane/ethyl acetate (1000 ml), ethyl acetate (400 ml), 80/20 acetone/methanol (500 ml): 30 fractions x 50 ml 1 x 200 ml Of fractions 21 and 22 received a yellow rubber-like substance, which by recrystallization from hexane gives the specified product with a melting point of 126-127aboutWith in the form of a yellow solid substances is giving 53).

A mixture of 1 g of 7-chloro-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 0,136 g LiOHH2O, and 2 ml of water and 10 ml of methanol is stirred until the morning when K. So the Mixture is evaporated to the dry state in a rotary evaporators. Further drying ("drymg pistol") gives the connection specified in the form of a solid substance with so pl. 153-157aboutC.

P R I m e R 10. 3-[(4,6-dimethoxy-alpha-hydroxy-2-pyrimidinyl)methyl]pyridine-2-carboxylate lithium (PL.5, the connection 64).

A mixture of 0,490 g of 5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4,b]pyridine-7(5H)-he 0,0768 g LiOH H2O. 10 ml of methanol and 2 ml of water is stirred for 24 h in nitrogen atmosphere at K. T. and the solvent is removed. Yellowish solid is dried for a further 2 hours to obtain the specified product with so pl. 250aboutC (decomposition).

P R I m e R 11. 2-Chloro-6-[(4,6-dimethoxy-2-pyrimidinyl)carbonyl]benzoate sodium (PL.4, the connection 58).

1.24 g of 7-Chloro-3-hydroxy-3-(4,6-dimethoxy-2-pyrimidinyl)phthalide, 154 mg of NaOH, 25 ml THF and 25 ml of water, mix until you get a yellow homogeneous solution. The solvent is removed on a rotary evaporators and then on "Kugelrohr" at 100aboutWith obtaining the target compound as yellow solids with so pl. 276-278aboutC.

P R I m e R 12. 3-[(4,6-Dimethoxy-2-pyrimidinyl)carbonin-7(5H)-he (490 mg) was dissolved in 50 ml of methanol and the mixture is heated, stirring, at 50aboutWith until it forms a homogeneous solution (about 0.5 h). NaOCl (2.6 g) is added dropwise and the solution is heated for another 0.5 h at 55aboutC. At this temperature, add 0,208 g 50% NaOH and the mixture is heated for another 0.5 h at this temperature and then cooled on ice and acidified with 1 ml concentrated HCl. The solvent is evaporated and the residue is divided between 50 ml of CH2Cl2and 50 ml of water. The organic phase is concentrated to obtain white solids with so pl. 71-73aboutC.

P R I m e p 13. 2-[(4,6-dimethoxy-2-pyrimidinyl)-alpha-aminomethyl]benzoic acid (PL.4, compound 51).

Isopropyl-2-bromobenzoate (2.67 g) was dissolved in 100 ml of anhydrous diethyl ether, the solution is cooled to -100aboutWith and add to 6.6 ml of a 1.6 M solution of n-utillity. Stirring is continued for 10 min and for 2 min add if -100aboutWith 12 g of 2-cyano-4,6-dimethoxypyrimidine in 60 ml of diethyl ether. The mixture is stirred for 0.5 h at -80aboutWith and then left to warm to room temperature. To the reaction mixture, cooled in a water bath, add 3 g of NH4Cl in 30 ml of water. The ether layer is separated, washed with water (2 x 30 ml) and concentrated. The viscous residue is dissolved in 20 ml of 85/15 hexane/this is the 500 ml of 1% methanol in ethyl acetate, 500 ml of 5% methanol in ethyl acetate and 500 ml of 80/20 acetone/methanol: 40 fractions 60 ml 1 x 200 ml Of fractions 7-10 got mentioned in the title compound which, after recrystallization from CH2Cl2melts at 225-235aboutC.

P R I m e R 14. 5-Chloro-5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4,b]pyridine-7(5H)-on (PL.3, the connection 68).

A mixture of 490 mg of 5-(4,6-Dimethoxy-2-pyrimidinyl)furo[3,4,b]pyridine-7(5H)-he and 50 ml of methanol is heated under 55aboutC for 0.5 h or until it forms a homogeneous solution. Added dropwise 2.6 g NaOCl (common household bleach). The mixture is placed in dichloromethane, the organic phase is separated and evaporated to remove water to obtain the specified connection.

P R I m e R 15. 3-[(4,6-Dimethoxy-2-pyrimidinyl)carbonyl]pyridine-2-carboxylic acid (PL.6, the connection 63).

0,208 g of 50% NaOH was added when 55oWith the solution of 0,551 g of 5-chloro-5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4,b]pyridine (PL.3, the connection 68) in 50 ml of methanol. The mixture was stirred for another 0.5 h at 55aboutC, cooled on ice, acidified with 1 ml concentrated HCl and the solvent evaporated. The residue was divided between 50 ml of CH2Cl2and 50 ml of N2Oh, when this layer CP>aboutC.

P R I m e R 16. 2-[2-(4,4-Dimethyloxazole-2-yl)-benzyl]-4,6-dichloropyrimidine (PL.4, the connection 61).

To a mixture of 1.25 g of 2-o-toluene-4,4-dimethyl-oxazoline in 20 ml of ether in a nitrogen atmosphere at -30aboutIt was added by syringe to 4.2 ml of 1.6 M n-utility in hexane with stirring, which was continued for 1 h at -10aboutC. To this reaction mixture was slowly added to 0.98 g of 4,6-dichloropyrimidine in 20 ml of ether, then stirred at (-45) (-30)aboutC for 30 min and at 0aboutWith another 30 minutes, the Reaction mixture was quenched with acetic acid (0.4 ml) and water (0.1 ml) in THF (1.3 ml), then treated with 1.5 g of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in 6 ml THF. The temperature is brought to K. T. and the mixture is stirred for 5 min after cooling to 0aboutAfter this 7,6 ml of chilled 1H. NaOH is added to the mixture and the mixture is stirred for 5 minutes the Organic phase is separated and dried over sodium sulfate, filter and remove the solvent. Subsequent chromatography (10/90 ether/hexane) to obtain the desired product.

P R I m e R 17. 2-[2-(4,4-Dimethyl-oxazoline-2-yl)-benzyl]-4,6-dimethoxypyrimidine (PL.4, the connection 48).

To a solution of 1.7 g of 2[2-(4,4-dimethyl-oxazoline-2-yl)benzene]-4,6-dichloropyrimidine in 100 ml of methanol add to 2.18 g of 25% aqueous methanol NaOCH

P R I m e R 18. 2-[2-(4,4-Dimethyl-oxazoline-2-yl)-alpha-bromobenzyl]-4,6-DiMeo-xipamide (PL.4, compound 62).

0.55 g of 2-[2-(4,4-dimethyl-oxazoline-2-yl)-benzyl]-4,6-dimethoxypyrimidine, of 0.30 g of N-bromosuccinimide, 0.03 g of benzoyl peroxide dissolved in 60 ml of CCl4and heated under reflux until the morning when the 75aboutC. the Reaction mixture is filtered and the filtrate washed with 5% NaHCO3solution (50 ml), 50 ml of water, the organic phase is separated and its concentration gives the target compound.

P R I m e R 19. 2-[2-(4,4-dimethyl-oxazoline-2-yl)-benzoyl]4,6-dimethoxypyridine - DIN (PL.4, the connection 49).

A mixture of 1.2 g of 2-[2-(4,4,-dimethyl-oxazoline-2-yl)-alpha-bromobenzyl]-4,6-DiMeo-xipamide on and 2 g of Na2CO3in 30 ml heated under stirring at 50-60aboutC for 3 hours the Mixture was poured into 150 ml of water and extracted with toluene. Toluene extract is washed twice with water (2 x 50 ml), separated and concentrated. Thus obtained rubber-like substance chromatographic with 800 ml of 80/20 hexane/ethyl acetate, 500 ml of 70/30 GE

P R I m e R 20. 2-Chloro-6-(4,6-dimethoxy-2-pyrimidinylidene)-benzoic acid dimethylamide (PL.4, the connection 57).

7-Chloro-3-cyano-3-(4,6-dimethoxy-2-PI-rimidine)phtalic (1 g) dissolved in 15 ml of THF, 0.7 ml of a 40% aqueous solution of dimethylamine, then add the syringe, and the solution darkens. Stirring is continued at K. I. for 15 min, the mixture was diluted with water and separated between ethyl acetate and water. The organic phase is separated, washed with 2n. H2SO4and then brine (saturated salt solution), dehydrate and concentrate. The residue is purified on silica gel, elute with 200 ml of 50% ethyl acetate/hexane, then 100% ethyl acetate. From fractions 12-15 receive the target connection with so pl. 141-142aboutC.

P R I m e R 21. 3-Acetoxy-7-chloro-3-(4,6-dimethoxy-2-pyrimidinyl)phtalic (PL.2, the connection 125).

7-Chloro-3-(4,6-dimethoxy-2-pyrimide-Neil)-3-hydroxyproline (1.1 g) was dissolved in 20 ml of pyridine and add 0.3 ml of acetic anhydride with stirring. After stirring for 20 min the mixture was poured into 2n. HCl and extracted with 2 hours of ethyl acetate. United an ethyl acetate extracts are washed once with 2n. HCl, once with water and once with saline and dehydrated over magnesium sulfate. Filtering and viparis="ptx2">

P R I m e R 22. 3-[(4,6-Dimethoxy-alpha-hydroxy-2-pyrimidinyl)methyl] pyridine-2-carboxamide (PL.6, the connection 82).

To a solution of 0.9 g of ammonium in 15 ml of methanol is added 0.5 g of 3-(4,6-dimethoxy-2-pyrimidinyl)-7-asafetida. After stirring for 2 h at K. I. methanol is removed under reduced pressure and the concentrate will recrystallized from toluene to obtain the desired compound in the form of a white solid with so pl. 135-137aboutC.

P R I m e R 23. 3[(4,6-Dimethoxy-4-hydroxy-2-pyrimidinyl)methyl]pyridin-2- [ carboxy-(4-isopropyl)anilide] (PL.6, the connection 183).

To a solution of 3 ml of 4-isopropylaniline in 50 ml of toluene inject 4 ml of 15.6% trimethylaluminum in hexane with K. So the Mixture is stirred for half an hour, by K. T., and add 0.5 g of 3-(4,6-dimethoxy-2-pyrimidinyl)-7-asafetida. The mixture is stirred for 2 h at K. T. and acidified with 30 ml of 10% hydrochloric acid at 5-10aboutC. the Toluene solution is separated, washed with 20 ml of 10% hydrochloric acid, 20 ml of 5% aqueous sodium carbonate and 20 ml of water, dehydrated and concentrated. The concentrate will recrystallized from hexane to obtain the target compound in the form of a white solid with so pl. 113-114aboutC.

P R I m e R 24. 3-](4,6-Dimethoxy-alpha-[ethoxycarbonyl]-2-Pirineos-2-pyrimidinyl)methyl] -Piri-DIN-2 - carboxamide, 0.5 g of 4-(dimethylamino)pyridine and 1 ml of triethylamine in 20 ml of toluene and 10 ml of dichloromethane was added 1 ml of ethylchloride at K. I. After stirring for 1 h at ambient temperature the mixture is washed with water (2 x 30 ml), dehydrated and concentrated on a rotary evaporators. The concentrate is treated with a volume mixture of hexane/toluene 10 ml at 50aboutC, cooled to K. T. and filtered to highlight 0.45 g of the compounds in the form of a yellow solid with so pl. 112-114aboutC.

P R I m e R 25. 3-[(4,6-Dimethoxy-alpha-benzoyloxy-2-pyrimidinyl)methyl] PI-ridin-2 -(N,N-Dibenzoyl)carboxamide (PL.6, compound 159).

To a solution of 0.05 g of 3-[(4,6-dimethoxy-alpha-hydroxy-2-pyrimidinyl)methyl] -2-CT-oxamide, 0.5 g of 4-(dimethylamino)pyridine and 4 ml of triethylamine in 30 ml of dichloromethane added 1.4 g of benzoyl chloride in K. So the two portions. The reaction mixture was stirred at K. T. for 17 h and washed with 30 ml of water, 30 ml of 5% hydrochloric acid and 30 ml of water. The dichloromethane solution concentrate and concentrate flashamateur in 300 ml of silica gel (230-400 mesh mesh) using 1 l 70/30 hexane/ethyl acetate and 500 ml of 50/50 hexane/ethyl acetate as an eluting solvent mixtures. From fractions 18-21 after recrystallization ptx2">

P R I m e R 26. 3-[(4,6-Dimethoxy-alpha-(N-methylcarbamoyl)-2-pyrimidinyl) methyl]-2-pyridine, carbox(N-allyl)amide (PL.6, the connection 133).

To a solution of 0.5 g of 3-[(4,6-dimethoxy-alpha-hydroxy-2-pyrimidinyl)-methyl] -2-pyridi-carbox(N-allyl)amide and 3 drops of triethylamine in 20 ml dichloromethane add 3 ml of methyl isocyanate in three portions of 1 ml / day under stirring at K. I. within 3 days. The reaction mixture was washed with water (2 x 50 ml), dehydrated and concentrated. Concentrate flashamateur in 300 ml of silica gel (230-400 mesh mesh) using 1 l of 50/50 hexane/ethyl acetate, 500 ml of ethyl acetate, 500 ml of an ethyl acetate 80/20 methanol, only 34 fractions (50 m/m). From fractions 21-25 obtain 0.4 g of the specified product as a yellow rubbery substance.

The compounds listed in table. 2-7, can be prepared similarly to the previous examples or otherwise, as described here.

NMR data of ['H nmr (CDCl3)]

NMR data of ['H nmr (CDCl3)]

Cpd N

41 of 3.95 (s, 6H, OCH3), 5-95 (s, 1H, pyrimidine H), of 6.45 (s, 1H, OCH), 7,7-9,1 (m, 3H, pyridine H).

44 : to 1.32 (t, 3H, CH3), 2,87 (q, 2H, CH2), of 4.05 (s, 6H, OCH3), and 6.3 (s, 1H, OCH), of 7.82 (d, 1H, arene), 8,72 (d, 1H, arene.).

46 : 1,32 (t, 3H, CH3), 2,85 (q, 2H, CH2), a 3.87 (s, 6H, OCH33), OF 3.95 (2H, OCH2) and 4.65 (s, 2H, CH2), to 5.85 (s, 1H, pyrimidine H), 7,2-8,0 (4H, aromatic).

49 : 1,00 (s, 6H, CH3), the 3.65 and 3.75 (d of d, 2H, OCH2), equal to 6.05 (s, 1H, pyrimidine H), a 7.2 to 8.1 (4H, fragrances H).

54 : 2,9 (s, 3H, CH3N) 3,10 (s, 3H, CH3O), 3,90 (s, 6H, fragrances co3), 6,10 (s, 1H, pyrimidine H), A 7.2 TO 7.9 (3H, fragrances H).

61 : 1,24 (s, 6H, CH3), 3,98 (s, 2H, CH2O), 4,74 (s, 2H, CH2), 7,16 (s, 1H, pyrimidine H).

65 : 3,96 (s, 6H, OCH3), 5,96 (s, 1H, pyrimidine H), 6,32 (s, 1H, OCH), 7,27 (d, 1H, thienyl N), the 7.85 (d, 1H, thienyl N).

66 : 4,08 (s, 6H, OCH3), 6,27 (s, 1H, OCH), 7,18 (d, 1H, thienyl N), of 7.95 (d, 1H, thienyl N).

76 : 1,63 (t, 3H, CH2CH3), 3,91 (s, 6H, OCH3), was 4.1 (q, 2H, OCH2), between 6.08 (s, 1H, pyrimidine H), 7,2-7,8 (m, 3H, fragrances H).

83 : 3,85 (s, 6H, OCH3), to 4.52-4.63 to (d, 2H, NCH2), to 5.21-5,42 (s, 1H, OH), 5,80 (s, 1H, OCH), PC 6.82 (s, 1H, pyrimidine), to 7.25 (s, 5H, aromatic), 7,31-7,52 (m, 1H, pyridine), 7,80-to 8.12 (d, 1H, pyridine), 8,35-8,55 (d, 1H, pyridine), 8,58-8,88 (s, 1H, NH).

84 : 3,85 (s, 6H, OCH3), of 4.05 (t, 2H, NCH2), 5,0-of 5.45 (m, 3H, CH=CH2), to 5.85 (s, 1H, pyrimidine), to 6.80 (s, 1H, OCH), a 7.2 to 8.6 (m, 3H, pyridine).

86 : 3,85 (s, OCH3), lower than the 5.37 (s, OCH2Ar), to 5.85 (s, pyrimidine), to 6.80 (d, OCH), a 7.2 to 8.2 (m, aromatic), mix with Conn. 40.

88 : 4,00 (s, 3H, OCH3), of 5.50 (s, 2H, OCH2), equal to 6.05 (s, 1H, pyrimidine H), 6,27 (s, 1H, O-CH), and 7.1 to 7.7 (m, 8H, fragrances H).

95 : 3,85 (s, iridin), 8,81-9,01 (d, 1H, pyridine).

97 : of 3.80 (s, 6H, OCH3), to 5.35 (s, 2H, OCH2Ar), 6,85 (s, 1H, pyrimidine), of 6.65 (s, 1H, OCH), 7,15 to 8.6 (m, 8H, aromatic), mix with Conn. 40.

107 : 1,92 (s, 3H, C=CCH3), 3,98 (s, 6H, OCH3), to 4.92 (s, 2H, OCH2), 6,07 (s, 1H, OCH), to 6.58 (s, 1H, pyrimidine), 7,52-7,88 (m, 1H, pyridine), 8,10-8,32 (d, 1H, pyridine), 8,90-8,91 (d, 1H, pyridine).

110 : 0,75-of 1.12 (t, 3H, CH3), 3,18-of 3.48 (m, 2H, CH2), 3,81 (s, 6H, OCH3), 4,42-4,91 (m, 3H, OH and NCH2), of 5.82 (s, 1H, OCH), 6,72 (s, 1H, pyrimidine), 7,21-7,52 (m, 1H, pyridine), 7,82-8,08 (d, 1H, pyridine), 8,32-8,61 (f, 1H, pyridine).

112 : of 1.12 to 1.31 (d, 6H, CH3), 3,81 (s, 6H, OCH3), 4,12-4,32 (m, 1H, NCH), to 5.85 (s, 1H, OCH), of 6.71 (s, 1H, pyrimidine), 7,21-7,52 (q, 1H, pyridine), 7,81-of 8.09 (d, 1H, pyridine), 8,12-8,31 (m, 1H, NH), 8,39-8,55 (d, 1H, pyridine).

119 : 3,05 (d, 3H, NCH3), of 3.94 (s, 6H, OCH3), 5,20 (s, 1H, OH), of 5.75 (s, 1H, OCH), 5,98 (s, 1H, pyridine H), 7,26 (d, 1H, pyridine H), 7,82 (q, 1H, NH), of 8.28 (d, 1H, pyridine H).

127 : 3,75 (s, 6H, OCH3), of 4.05 (t, 2H, NCH2), of 5.05 to 5.5 (m, 3H, CH=CH2), to 5.85 (s, 1H, pyrimidine), a 7.2 to 8.6 (m, 9H, fragrances +core).

128 : of 2.20 (s, 3H, CH3in ), 3.75 (s, 6H, OCH3), 4,10 (t, 2H, NCH2), a 5.0 to 6.6 (m, 3H, CH=CH2), to 5.85 (s, 1H, pyrimidine), a 7.2 to 8.6 (m, 5H, pyridine + NH, OCH).

130 : 0,75-to 1.61 (m, 15H, alipate), 1,61-to 3.02 (m, 8H, alipate), 3,15-3,61 (m, 2H, NC2), 3,81 (s, 6H, OCH3), of 5.82 (s, 1H, OCH), for 6.81 (s, 1H, pyrimidine), 7,21-7,52 (q, 1H, pyridine), 7,92-of 8.15 (d, 1H, pyridine), 8,17-8,32 (m, 1H, NH), 8,35-charged 8.52 (d, shall eremein), of 7.2 and 8.6 (m, 4H, pyridine + core).

150 as 0.96 (t, 3H, CH3), by 1.68 (m, 2H, CH2CH2CH3), a 3.50 (m, 2H, NCH2), 3,93 (s, 6H, OCH3), of 5.92 (s, 1H, pyrimidine H), 6,17 (d, 1H, OCH), 7,21 (d of d, 1H, pyridine H), 8,07 (d of d, 1H, pyridine H), to 8.57 (d of d, 1H, pyridine H), 8,66 (t, 1H, NH).

151 : 1,41-to 1.61 (d, 3H, CH3), 3,82 (s, 6H, OCH3), 4,92 to 5.35 (m, 2H, NCH, OH), of 5.81 (s, 1H, OCH), 6,85 (s, 1H, pyrimidine), 7,12-7,51 (m, 6H, fragrances and pyridine), 7,82-8,10 (d, 1H, pyridine), scored 8.38-of 8.50 (d, 1H, pyridine), 8,51--8,82 (m, 1H, NH).

152 : to 2.25 (s, 3H, CH3), the 3.89 (s, 6H, OCH3), 3,42-3,61 (d, 2H, NCH2), of 5.81 (s, 1H, OCH), 6,85 (s, 1H, pyrimidine), 7,03 (s, 4H, aromatic), 7,12-7,52 (q, 1H, pyridine), a 7.85-to 8.12 (d, 1H, pyridine), 8,40-8,51 (d, 1H, pyridine), 8,58-8,72 (m, 1H, NH).

171 : 1,24 (t, 3H, CH3), 2,60 (q, 2H, CH2), 3,86 (s, 6H, OCH3), to 4.62 (d, 2H, NCH2), 5,86 (s, 1H, pyrimidine H), of 6.90 (d, 1H, OCH), 7,0-8,54 (m, 7H, fragrances H), at 8.60 (bs, 1H, NH).

174 : a 3.83 (s, 3H, OCH3), 3,90 (s, 6H, OCH3), of 5.83 (s, 1H, pyrimidine H), 6,60 (d, 1H, OCH), 7,30 (d of d, 1H, pyridine H), 8,23 (d of d, 1H, pyridine H), to 8.70 (d of d, 1H, pyridine H).

177 : 2,20 (s, 6H, CH3), 2,31-2,60 (m, 2H, CH2N), 3,31 of 3.75 (q, 2H, NCH2), of 3.78 (s, 6H, OCH3), of 5.75 (s, 1H, OCH), is 6.61 (s, 1H, pyrimidine), 7,13-7,42 (q, 1H, pyridine), 7,71-to $ 7.91 (d, 1H, pyridine), 8,31-8,51 (d, 1H, pyridine).

178 : 3,85 (s, 9H, OCH3), of 3.95 (s, 3H, OCH3), 4,14 (s, 2H, CH2), of 5.82 (s, 1H, pyrimidine H), of 6.90 (d, 1H, pyridine H) to 8.12 (d, 1H, pyridine H).

196 : of 3.78 (s, 6H, OCH3), 4,51-4,78 (d, 2H, NCH2), to 5.35 (s, 1H, OH), of 5.81 (s, 1H, OCH), 6,28 (s, 2H, furfuryl), for 6.81 (s, 1H, pyrimidine), 7,12-the 7.43 (m, 2H, furfuryl), 7,82-with 8.05 (d, 1H, pyridine), 8,31-8,43 (d, 1H, pyridine), charged 8.52-8,71 (m, 1H, NH).

201 : 1,87-2,04 (m, 4H, CH2and tetrahydrofuran), 3,71-to 3.92 (m, 9H, OCH3and tetrahydrofuran), 5,86-by 5.87 (m, 2H, OCH and OH), of 6.71 (d, 1H, pyrimidine), 7,31-7,42 (d, 1H, pyridine), 7,81-a 7.92 (d, 1H, pyridine), to 8.41-of 8.50 (d, 2H, NH and pyridine).

206 : 2,22 (s, 1H, CH3), 3,85 (s, 6H, OCH3), to 3.92 (s, 3H, OCH3), of 3.97 (s, 3H, OCH3), 5,86 (s, 1H, pyrimidine H), to 6.80 (s, 1H, OCH), 7,10 (d, 1H, pyridine H), 8,16 (d, 1H, pyridine H).

209 : 3,63-3,74 (t, 9H, OCH3), 5,48-of 5.81 (m, 4H, CHO, OH, COCH), 6,88-7,42 (m, 8H, phenyl, pyrimidine, pyridine), 7,94-of 7.97 (d, 1H, pyridine), 8,45-of 8.47 (d, 1H, pyridine), 9,24-9,26 (d, 1H, NH).

212 : 3,85 (s, 6H, OCH3), to 4.41-to 4.52 (m, 2H, NCH2), to 5.21-5,72 (d, s, 4H, NH2, OCH, OH), is 6.61 (s, 1H, pyrimidine), 7,12-to 7.32 (m, 3H, pyridine, bansilalpet), 7,71-7,80 (m, 3H, pyridine, bansilalpet), and 8.3 (d, 1H, pyridine), 8,71 (m, 1H, NH).

213 : 3,61 (s, 6H, OCH3), 4,60-by 5.18 (m, 3H, ArCH2, OH), 5,72 (s, 1H, OCH), 6,72 (s, 1H, pyrimidine), 7,15-7,17 (t, 5H, pyridine), 7,84-7,86 (d, 1H, pyridine), scored 8.38-8,44 (d, 2H, pyridine), 9,12 (s, 1H, NH)

214 : 3,75 (s, 6H, OCH3), 4,72-4,74 (d, 2H, N-to 8.40 (d, 1H, pyridine), 8,71 (d, 1H, NH).

216 : to 1.31 (t, 3H, CH3), 2,62 (s, 3H, CH3), a 3.87 (s, 6H, OCH3), is 4.21 (s, 2H, CH2), and 4.40 (q, 2H, OCH2), of 5.83 (s, 1H, pyrimidine H), 7,13 (d, 1H, pyridine H), 8,44 (d, 1H, pyridine H).

218 : 284 (is 3.08) (s, 3H, NCH3), to 3.92 (s, 6H, OCH3), 4,50-to 5.03 (m, 2H, NCH2), 6,10 (s, 1H, pyrimidine H), 7,10-7,80 (m, 7H, fragrances H).

227 : 1,50 (m, 6H, CH2), is 2.40 (m, 6H, NCH2) 3,55 (q, 2H, NCH2), of 3.80 (s, 6H, OCH3), to 5.85 (s, 1H, pyrimidine H) 6,70 (s, 1H, OCH), 7,15-at 8.60 (m, 1H, 3 pyridine N + NH).

233 : 1,80 (q, 2H, CH2in ), 2.25 (s, 6H, NCH3), to 2.35 (q, 2H, NH2), of 3.45 (q, 2H, NCH2), of 3.80 (s, 6H, CH3), 5,80 (s, 1H, pyridine), of 6.65 (s, 1H, OCH), 7,15-of 8.50 (m, 3H, pyridine).

234 : 1,00 (t, 6H, CH3), 2,60 (m, 6H, NCH2), a 3.50 (q, 2H, NCH2), to 3.92 (s, 6H, OCH3), 5,80 (s, 1H, pyrimidine H), to 6.80 (s, 1H, OCH), 7,15-8,7 (m, 3H, pyridine).

236 : to 1.37 (t, 3H, CH3), of 2.56 (s, 3H, CH3), a 3.87 (s, 6H, OCH3), 4,43 (q, 2H, OCH2), by 5.87 (s, 1H, pyrimidine H), 6,12 (s, 1H, CHBr), of 7.90 (d, 1H, pyridine H), 8,56 (d, 1H, pyridine H).

237 : of 1.40 (t, 3H, CH3), a 3.87 (s, 6H, OCH3), 4,43 (q, 2H, OCH2), 4,70 (s, 2H, CH2Br), 5,88 (s, 1H, pyrimidine H), 6,23 (s, 1H, CHBr), 8,07 (d, 1H, pyridine H), 8,65 (d, 1H, pyridine H).

238 : to 1.37 (t, 3H, CH3), to 2.06 (s, 3H, CH3), 3,88 (s, 6H, OCH3), and 4.40 (q, 2H, OCH2), 5,28 (s, 2H, OCH2), by 5.87 (s, 1H, pyrimidine H), 6,23 (s, 1H, CHBr), of 8.04 (d, 1H, pyridine H) 8,64 (d, 1H, pyridine ), 7,32-7,38 (m, 6H, pyridine, aromatic), 7,94-7,98 (d, pyridine), 8,45-8,49 (d, 1H, pyridine), of 9.55 (s, 1H, NH).

264 : 0,8-1,9 (brs, 25H, alipate), 3,85-are 3.90 (s, 6H, 2XOMe), x 6.15 (s, 1H, ArH, pyrimidine), and 7.4 (s, 2H, ArH).

277 : of 0.90 (t, 3H, CH3), 1,2-1,7 (m, 4H, alipate), of 3.95 (s, 6H, OCH3), 4,08 (t, 2H, OCH2), x 6.15 (s, 1H, pyrimidine H), of 7.5 to 7.7 (m, 3H, aromatic).

281 : of 0.90 (t, 3H, CH3), 1,3 (m, 4H, alipate), and 1.6 (m, 2H, alipate), of 3.95 (s, 6H, OCH3), 4,08 (t, 2H, OCH2), x 6.15 (s, 1H, pyrimidine H), of 7.4 to 7.7 (m, 3H, aromatic).

283 : 3.40 in (s, 6H, OCH3), of 3.43 (m, 2H, NCH2), 3,82 (s, 6H, OCH3), 4,47 (t, 1H, CH), 5,86 (s, 2H, OCH, OH), 6,77 (s, 1H, pyrimidine), 7,41-the 7.43 (m, 1H, pyridine), 7,94-7,98 (d, 1H, pyridine), of 8.47-8,48 (d, 1H, NH).

284 : 1,71 to 1.76 (s, 6H, CH3), 2,31 (s, 1H, C=CH), 3,82 (s, 6H, OCH3), 5,61-5,63 (d, 1H, OH), to 5.85 (s, 1H, OCH), 6,86-of 6.96 (d, 1H, pyrimidine), 7,44-of 7.48 (m, 1H, pyridine), 7,94-7,98 (d, 1H, pyridine), 8,44-to 8.45 (d, 2H, NH).

285 : 0,75-of 1.13 (m, 4H, alipate), 1,28-to 1.77 (m, 3H, alipate), 3,23-to 3.52 (m, 2H, NCH2), 3,82 (s, 6H, OCH3), 5,73-5,88 (m, 2H, OH, OCH), 6,60-for 6.81 (d, 1H, pyrimidine), 7,21 was 7.45 (q, 1H, pyridine), 7,78 shed 8.01 (d, 1H, pyridine), 8,32-8,55 (d, 2H, pyridine, NH).

286 : 1,21-1,32 (d, 2H, CH2O), 3,38-to 3.58 (d, 6H, CH3), 3,85 (s, 6H, OCH3), 4,18-4,48 (m, 2H, NCH, OH), 5,88 (s, 1H, OCH), was 6.73 (s, 1H, pyrimidine), 7,28-7,52 (q, 1H, pyridine), 7,81-8,08 (d, 1H, pyridine), 8,43-to 8.62 (d, 2H, pyridine, NH).

290 : 3,74 (s, 9H, OCH3), 5,44 (bs, 1H, OH), 5,73 (s, 1H, pyrimidine), 6,62 (bs, 1H, OCH), the 6.9 to 8.6 (m, fragrances, 7H), 10,22 (s, 5,80 (s, 1H, pyrimidine), 6,70 (s, 1H, OCH), a 7.2 to 8.6 (m, 4H, pyridine H + HE).

292 : to 1.60 (m, 4H, CH2in ), 2.25 (s,6H, NCH3in ), 2.25 (m, 2H, NCH2), of 3.48 (m, 2H, NCH2), the 3.65 (s, 6H, OCH3), 5,80 (s, 1H, pyrimidine), of 6.65 (s, 1H, OCH), a 7.2 to 8.6 (m, 4H, pyridine +HE).

295 : 3,74 (s, 6H, OCH3), of 3.80 (s, 6H, OCH3), 4,50 (d, 2H, NCH2), of 5.84 (s, 1H, pyrimidine), a 6.5 and 8.6 (m, 8H, fragrances, OCH, NH).

297 : the 3.65 (s, 6H, OCH3), of 3.77 (s, 6H, OCH3), 4,50 (d, 2H, NCH2), 5,64 (d, 1H, OH), 5,80 (s, 1H, pyrimidine), 6,25-6,60 (m, 3H, aromatic), 6,8 (d, 1H, OCH), a 7.2 to 8.6 (m, 3H, pyridine).

298 : 3,82 (s, 6H, OCH3), of 5.81 (s, 1H, OCH), 6,29-7,58 (m, 8H, OH, NH, pyrimidine, fragrances, pyridine) 7,80 is 8.25 (d, 1H, pyridine), of 8.47-to 8.62 (d, 1H, pyridine), 9,74-to 9.93 (br, 1H, NH).

299 : of 0.85 (t, 3H, CH3), 1,2 (m, 8H, alipate), and 1.6 (m, 2H, alipate), of 3.95 (s, 6H, OCH3), 4,08 (t, 2H, OCH2), x 6.15 (s, 1H, pyrimidine H), of 7.4 to 7.7 (m, 3H, aromatic).

300 : 0,90 (t. 3H, CH3), 1,2 (m, 10H, alipate), and 1.6 (m, 2H, alipate), of 3.95 (s, 6H, OCH3), 4,08 (t, 2H, OCH3), 4,08 (t, 2H, OCH2), x 6.15 (s, 1H, pyrimidine H), of 7.4 to 7.7 (m, 3H, aromatic).

303 : of 3.80 (s, 6H, OCH3), 3,90 (d, 6H, OCH3), the 5.45 (d, 1H, OH), 5,80 (s, 1H, pyrimidine), 6,85 (s, 1H, OCH), a 7.0 and 8.6 (m, 6H, aromatic), 10,2 (s, 1H, NH).

305L(-) : to 1.60 (d, 3H, CH3in ), 3.75 (2s, 6H, OCH3in ), 5.25 (m, 1H, OH), of 5.75 (s, 1H, pyrimidine), to 6.75 (d, 1H, OCH), a 7.2 to 8.6 (m, 8H, aromatic).

308 : to 0.88 (t, 3H, CH3), 1,25 (bs, 17H, alipate), and 1.6 (m, 2H, alipate), of 3.95 (s, 6H, OCH3(CH3)2), 2,3 (m, 4H, NCH2), and 3.8 (s, 6H, OCH3), and 5.8 (s, 1H, pyrimidine H) and 5.9 (s, 1H, CH-Ot-Bu), 7,18 (d of d, 1H, pyridine H), was 7.45 (d of d, 1H, pyridine H), and 8.6 (d of d, 1H, pyridine H).

407 : 3,18 (m, 2H, CH2S), the 3.65 (m, 2H, CH2N) of 3.95 (s, 6H, OCH3), to 5.85 (s, 1H, pyrimidine), to 6.80 (s, 1H, OCH), 7,0-to 8.7 (m, 8H, aromatic).

411 : 1,90 (t, 3H, CH3), of 1.55 (m, 4H, CH2), to 2.65 (m, 4H, CH2), 3,62 (m, 2H, CH2N), 3,82 (s, 6H, CH3O) 5,90 (s, 1H, pyrimidine), to 6.75 (s, OCH), 7,2-8,65 (m, 3H, pyridine).

412 : to 1.37 (s, 9H, tBuO), 3,30 (s, 3H, CH3N), 3,90 (s, 6H, CH3), 5,95 (s, 1H, pyrimidine), 5,97 (s, 1H, OCH), 6.5 to about 7.6 (m, 10H, aromatic).

413 : 2,23 (s, 1H, C=CH), 3,12-3,23 (d, 3H, N-CH3), 3,93 (s, 8H, OCH3N-CH2C= ), 6,155 (s, 1H, pyrimidine), 7,47-7,52 (m, 1H, pyridine), 8,142-8,168 (m, 1H, pyridine), 8,69-8,709 (t, 1H, pyridine).

P R I m e R 27. The method according to variant I(i).

Getting amide 3-[(4,6-dimethoxy-2-pyrindine)-hydroxymethyl]-N-methyl-2-pyridine carboxylic acid (compound 108, PL.6).

The reaction scheme

< / BR>
(compound 40/ table.3) Amide 3-[(4,6-dimethoxy-2 - 5-(4/6-dimethoxy-2-pyrimidyl)- pyrindine)-hydroxymethyl] furo-[3/4 in]-pyridyl-7(5H)-he-N-methyl-2-pyridine

C13H11N3O4carboxylic acid

273,25 C14H16N4O4< / BR>
304,31

Output: 99/0%

Educt:

30 g (109/8 Methanol

Three-neck flask (500 ml) equipped with a tube for input gas is lowered below the level of the solvent, a magnetic stirrer, a pocket for a thermometer and a tube for the gas outlet (needle valve). Reverse trap is placed between a gas cylinder with methylamine and a gas-feeding tube. The flask was dried at 140aboutIn nitrogen atmosphere, cooled to room temperature and loaded with methanol (300 ml), dried over molecular sieves 4. Methylamine gas (7.2 g, 231,8 mmol) bubbled in for 10 min at 10about(Vodoledyanym bath); 5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4-b] -pyridine-7(5H)-on (30 g, 109,8 mmol) added in one portion and the mixture stirred at room temperature for 14 h

The reaction mixture changed from red suspension until a homogeneous orange solution. The reaction can be monitored by thin-layer chromatography plate with silica gel using 100% ethyl acetate (Rf0.6 to 5, 0.50 to 8) or gas chromatography DB-5 capillary column 40 _ 300about(15aboutC) min).

The reaction mixture when suction filtered to remove insoluble particles and the filtrate evaporated on a rotary evaporator to a volume of 50 ml. Cooling, the suspension is cooled to 10about(Vadalabene and concentrate (2 g) is crystallized from 10 ml of methanol to obtain 1.8 g of product. The total yield of 33.3 g (99,6%), so pl. 132-133aboutC.

1H-NMR (CDCl3) : 8,70-7,30 (m, 3H, pyridine), 6,85 (g, 1H, och), to 5.85 (s, 1H, pyrimidine), 5,75 (g, 1H, HE), 3,85 (s, 6N, co3), 3,00 (g, 3H, NCH3).

P R I m e R 28. The method according to option 1(j).

Getting 4,7-dichloro-3-(4,6-dimethoxy-2-pyrimidinyl)-3-hexanoate-phthalide (compound 265, PL.2).

The reaction scheme

< / BR>
(compound 250, PL.2). 4,7-Dichloro-3-(4,6-dimethoxy-2-

4,7-Dichloro-3-(4,6-dimethoxy-2 - pyrimidinyl)-3-hexanolactone

pyrimidinyl)-3-hydroxyphthalic

C14H10Cl2N2O5C20H20Cl2N2O6< / BR>
357,15 455,30

Yield: 75%

Educt:

52 g (159,6 mmol) of 4,7-Dichloro-3-(4,6-dimethoxy-2-

pyrimidinyl)-3-hydroxyphthalic

35.2 g (164,25 mmol) Hexane anhydride

23,0 ml (165 mmol) Triethylamine

1.1 g (9.0 mmol) of 4-dimethylaminopyridine (DMAP)

500 ml of Dichloromethane

In one litre round-bottom flask equipped with a magnetic stirrer, was loaded with 500 ml of dichloromethane and 52 g (159,6 mmol) hydroxyproline and cooled in an ice bath. Add triethylamine (23 mmol) and DMAP (1.1 g) and the mixture is stirred until until a large part of the solid product is dissolved. Fresh is the 48 h at room temperature. The solution is then washed h ml of 1 N. H2SO4, CH ml of 0.1 G. of NaOH and brine, dried over Na2SO4and evaporated obtaining to 58.2 g of crude product (94,3% purity by GC). The solid product fray with 150 ml of E t2O and collected with suction, the filtrate obtaining and 49.2 g of the product. The filtrate is evaporated and purified by flashamature over 140 g of SiO2, eluent 30% tOA C/hexane, collecting 50 ml fractions. Fractions 3-12 inclusive gather, getting 6.5 g of crude product which is recrystallized from 10 ml tOAC/100 ml of hexane to obtain another 5.7 g of pure product. Total yield 54,67 g, so pl. 103-105aboutWith (purity, 95.4 percent).

NMR (acetone-d6): 0,86-of 0.91 (m, 3H, CH2CH3), 1,31-of 1.39 (m, 4H, -CH2CH2CH3), 2,5-2,6 (m, 2H, COCH2), a 3.87 (c, 6H, -OCH3), 6,15 (c, 1H, pyrimidinyl N) 7,75 (g, 1H, J 8.5 Hz, ArH), 7,80 (g, 1H, J 8.5 Hz, ArH).

P R I m e R 29. The method according to option 1 (k).

Getting amide 3-[(4,6-dimethoxy-2-pyrimidinyl)-carbonyl] -N,N-dimethyl-2 - pyridine carboxylic acid (compound 385, PL.6).

The reaction scheme

< / BR>
(compound 68/ table.3) Amide 3-[(4,6-dimethoxy-2-pyrimidinyl)

5-Chloro-5-(4/6-dimethoxy-2- -carbonyl]-N,N-dimethyl-2-

pyrimidinyl)-furo-[3/4-6] pyridineboronic acid

pyridine-7(5H)-he

36 (117 mmol) of 5-Chloro-5-(4/6-dimethoxy-2-

pyrimidinyl)-furo-[3/4-6]

pyridine-7(5H)-he

15/8 g (351 mmol) Dimethylamine/ gas

350 ml of Dichloromethane

Three-neck flask (500 ml) equipped with a mechanical stirrer, a tube for input gas is lowered below the level of the solvent, the receiver for a thermometer and a gas outlet (needle valve) (reaction flask dried in the assembled state in a nitrogen atmosphere using a heat pump).

Through a mixed solution of 36 g (116,99 mmol) 5-chloro-5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4-b] -pyridine-7(5H)- it is in dichloromethane (350 ml), cooled in a water bath, miss anhydrous gaseous dimethylamine (15,8 g, 351 mmol) (reverse trap is placed between the tank with gaseous dimethylamine and gasovodnog tube). Remove vodoledyanym bath and the solution was stirred at room temperature overnight. The reaction mixture was washed with saturated saline solution (g ml), passed through fathersday paper filter and the filtrate is evaporated on a rotary evaporator. The concentrate was dissolved in dichloromethane (200 ml), treated with activated charcoal at room temperature for one hour when suction filtered through the filter material. The filter is treated 1 h at 35aboutWith and left to crystallize overnight at room temperature. Precipitated solid product with suction filter and excrete 31,15 g of the product, so pl. 124-126aboutC. the Filtrate is evaporated (2,35 g oil) and flashamateur through 300 g of silica gel 230-400 mesh mesh using 1 l of ethyl acetate, 500 ml of 90/10 V/V ethyl acetate/methanol, 1 l 80/20 V/V acetone/methanol as an eluting solvent to obtain 40 50 ml fractions. From 18-22 factions gain of 1.32 g of product. Receive product with a total weight of 36,42 g (98.4% of output), so pl. 124-126aboutC.

1H-NMR (CDCl3) : 8,70 (gg, J of 1.4 and 4.9 Hz, 1H, ArH); 8,18 (gg, J of 1.4, 7.9 Hz, 1H, ArH), 7,44 (gg, J is 4.9, 7.9 Hz, 1H, ArH), 6,16 (s, 1H, pyrimidine), of 3.95 (s, 6N, co3), of 3.12 (s, 3H, NCH3), 2,96 (c, 3H, NCH3).

The METHOD of OBTAINING SUBSTITUTED FALICOV OR HETEROCYCLIC FALICOV General formula

< / BR>
where ring a is selected from the group comprising residues: phenyl, pyridyl, five-membered heteroaromatic ring containing oxygen, sulfur or nitrogen as a heteroatom;

R cyano, carboxyl group, which may be in the form of the free acid, or ester, or salts, carnemolla group, or mono-or disubstituted carnemolla group, or ring

< / BR>
Y1, Y2and Y-alkyl, C2-C8-alkenyl, C1-C8-alkoxy, C2-C8-alkenylamine, C2-C8-alkyloxy, C1-C8-alkylsulfonate, each of which, in turn, may be substituted by 1 to 6 halogen atoms and conjugated C1-C8-alkoxy, C2-C8-acyl, phenyl, C1-C8-alkoxyl, phenylthio, each of which can be substituted one or three halogen atoms;

Y1and Y2taken together with the adjacent carbon atoms form a group-C(O)-O-CH2;

W1, W2, W3, W4and W5each independently CH, CR3or N;

Z is a bridge consisting of elements selected from the group of methylene, substituted methylene, -C(O)-;

R1and R3each independently hydrogen, halogen, C1-C8-alkyl, C1-C8-alkoxy, C2-C8-alkenylamine, C2-C8-alkyloxy, each of which may be in turn substituted 1 6 halogenatom, 5 - or 6-membered heterocycle-C1-C8-alkoxy, phenyloxy or phenyl-C1-C8-alkoxy, each of which may be substituted by 1 to 3 substituents selected from a halogen or C1-C8-alkyl;

R2C1-C8-alkyl, Hairdryer who>C8-alkyl, C1-C8-alkoxy, C1-C8-alkoxycarbonyl, C2-C8-acyloxy, carbamoylated, C1-C8-alkylthio, phenyloxy, phenyl S, each of which, in turn, may be substituted by 1 to 3 halogen atoms or together they predstavlyayte,S,NH,NOR12or CR13R17or X and R together may form a bridge having the formula-C(O)-O - or-C(O)-NR2- where the carbonyl is attached to AND,

provided that when R carboxyl in free ether or salt and X and Y together are 0, then one of the rings a and b contains a heteroatom,

characterized in that:

a) when X and R are combined with the formation of the bridging group as defined above, and Y is hydrogen, cyano or aaltio carry out the reaction of compounds of General formula II

< / BR>
where ring A, Y1, Y2and Y3have the specified values;

Y is hydrogen, cyano or aaltio;

Z1oxygen, sulfur or NR2where R2has the specified values,

with a compound of General formula III

< / BR>
where W1, W2, W3, W4and R1have the specified values;

R21methylsulphonyl or halogen,

to obtain the corresponding compounds of formula Ip

(I) by hydrolysis to obtain the corresponding compound of formula I, where R and X form a bridge, and Y is hydroxyl, or a compound of formula I, where X and Y together form 0;

(II) is treated with an amine to obtain the corresponding compounds of formula I, where R is a possibly substituted carbamoyl group, and X and Y together form 0;

(III) connection MOR22where M is alkali metal, and R22hydrogen or C1-C8- alkyl,

to obtain the corresponding compound where R and X form a bridge, and Y is hydroxyl or C1-C3-alkoxyl, or

c) carry out the hydrolysis of compounds of formula Ip, where Y is hydrogen, Z1oxygen and other symbols have the listed values, to obtain the compounds of formula I, where R is a carboxyl group, possibly in the form of a salt, X is hydrogen and Y is hydroxy, followed, if necessary, by putting it in salt, or

d) open ring in the compound of formula Ip, where Y is hydroxyl, Z1oxygen and other symbols have the listed values, obtaining the compounds of formula I, where R is a carboxyl group, possibly in the form of salt, and X and Y together form 0;

e) atrificial compound of formula I, where R is a carboxyl group, possibly in the form of a salt, X and Y 0 dropgroup in the form of ether;

f) halogenous compound of formula Ip where Y is hydroxyl, Z1matter in part (a), the other symbols have the listed values by obtaining the compounds of formula I, where X and R together form a bridging group, and Y is halogen;

g) carry out the reaction of compounds of formula Ip, where Z1oxygen, Y is halogen, and other symbols have the above meanings, with a compound RNH2and HOR23where R2has the above significance, and R23C1-C8-alkyl, C2-C8-acyl or aryl, to obtain the corresponding compounds where Z1NR2and Y - C1-C8-alkoxy, aryloxy or C2-C8-acyloxy;

h) carry out the oxidation of compounds of formula Ip, where Y is hydrogen, Y1matter in part (a), the other symbols have the listed values, to obtain the corresponding compound where Y is hydroxyl;

i) interact connection Ip, where Z1oxygen, Y is hydrogen, the other symbols have the above meanings, with a group of R7NH2where R7-C1-C6-alkyl, to obtain the compounds of formula I, where R is monosubstituted carbarnoyl, X is hydrogen, Y is hydroxyl;

j) acelerou compound of formula Ip, where Z1oxygen, Y is hydroxyl, the other UB>8
-acyloxy;

(k) carry out the reaction of compounds of formula Ip, where Z1oxygen, Y is halogen, and other symbols have the listed values with connection R7R8NH, where R7matter in part i), R8= R7obtaining the compounds I where R carbarnoyl, disubstituted by lower alkyl, and X and Y together represent 0,

with subsequent isolation of the target product.

 

Same patents:

The invention relates to a method for obtaining new pyrimidine derivatives possessing valuable fungicidal properties, which can find application in agriculture

The invention relates to pyrimidine derivative of the General formula I:

where R1- alkyl-(C1-C4), O-alkyl-(C1-C4), halogen;

R2- alkyl-(C1-C4), O-alkyl-(C1-C4);

n = 3-5;

Z = COOH, COO-alkyl-(C1-C4), CONHSO2C6H5with herbicide activity, and to a method of controlling undesirable vegetation by processing them in the locus, namely, that the treatment is carried out pyrimidine derivatives of General formula I:

where R1- alkyl-(C1-C4), O-alkyl-(C1-C4), halogen;

R2- alkyl-(C1-C4), O-alkyl(C1-C4);

n = 3-5;

Z = COOH, COO-alkyl-(C1-C4), CONHSO2C6H5in the amount of 1-10 kg/ha

The invention relates to methods of producing derivatives of 2-anilinopyrimidines or acid additive salts of novel biologically active compounds, which can find application in agriculture

FIELD: organic chemistry, agriculture.

SUBSTANCE: method involves carrying out a seasonal single treatment of plant leaves with asymmetrical derivative of 4,6-bis-(aryloxy)pyrimidine of the formula: wherein X means chlorine atom (Cl), nitro- or cyano-group. Invention provides enhancing the long-term time of plants protection.

EFFECT: enhanced effectiveness and valuable properties of compounds.

6 cl, 6 tbl

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrimidine of the general formula (I) and their pharmaceutically acceptable acid-additive salts possessing properties of neurokinin-1 (NK) receptors antagonists. In the general formula (I): R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)n-N(R)2, -N(R)2 or cyclic tertiary amine as a group of the formula: R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)-N(R)2, -N(R)2 or cyclic tertiary amine of the formula: that can comprise additional heteroatom chosen from atoms N, O or S, and wherein this group can be bound with pyrimidine ring by bridge -O-(CH2)n-; R2 means hydrogen atom, lower alkyl, lower alkoxyl, halogen atom or trifluoromethyl group; R3/R3' mean independently of one another hydrogen atom or lower alkyl; R4 means independently of one another halogen atom, trifluoromethyl group or lower alkoxyl; R means hydrogen atom or lower alkyl; R means independently of one another hydrogen atom or lower alkyl; X means -C(OH)N(R)- or -N(R)C(O)-; Y means -O-; n = 1, 2, 3 or 4; m means 0, 1 or 2. Also, invention relates to a pharmaceutical composition comprising one or some compounds by any claim among claims 1-19 and pharmaceutically acceptable excipients. Proposed compounds can be used in treatment, for example, inflammatory diseases, rheumatic arthritis, asthma, benign prostate hyperplasia, Alzheimer's diseases and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

21 cl, 1 tbl, 76 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a novel method that can be used in industry for synthesis of substituted aniline compound represented by the following general formula (6):

wherein in the general formula (6) each R1, R2 and R3 means independently alkyl group, alkoxy-group, alkoxyalkyl group, halogenalkyl group, carboxyl group, alkoxycarbonyl group, alkylcarboxamide group, nitro-group, aryl group, arylalkyl group, aryloxy-group, halogen atom or hydrogen atom; each X and Y means independently hydrogen atom, alkyl group, alkoxy-group, alkoxyalkyl group, halogenalkyl group, carboxyl group, alkoxycarbonyl group or halogen atom. Method involves oxidation of substituted indole compound represented by the following general formula (3):

(wherein values R1, R2, R, X and Y are given above) resulting to opening indole ring to yield acetanilide compound represented by the following general formula (4):

(wherein values R1, R2, R3, X and Y are given above) and Ac means acetyl group, and treatment of this compound by reduction and deacetylation. Also, invention relates to novel intermediate compounds. Proposed compound (6) can be used as intermediate substance for production of chemicals for agriculture and as medicinal agents.

EFFECT: improved method of synthesis.

20 cl, 1 sch, 3 tbl, 31 ex

FIELD: organic chemistry, herbicides, chemical technology.

SUBSTANCE: invention relates to derivatives of substituted sulfonylaminomethylbenzoic acid of the general formula (I): wherein R1 means hydrogen atom (H) or (C1-C8)-alkyl; R2 and R3 mean H; R4 and R5 mean H; R6 means H or (C1-C8)-alkyl; R7 means (C1-C8)-alkyl; R8 is similar or different and means (C1-C4)-alkyl or (C1-C4)-alkoxy-group; n means 0 or 1. Compounds of the formula (I) are intermediate substances in synthesis of biologically active compounds possessing the herbicide activity, in particular, in synthesis of sulfonylureas. Also, invention describes methods for synthesis of compounds of the formula (I) and their derivatives.

EFFECT: improved method of synthesis.

27 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the new method of producing formerly unknown 1-(pyrimidine-2-il)propane-2-on of the general formula wherein R designates every time the C1-C10 alkyl group. The method consists in that the reaction of malone diimidate is carried out with the general formula , wherein R has the above-stated magnitudes, with dikenete of the formula . It is preferable to use malone diimidate (II) produced in situ from is appropriate salt and base. Here, the salt of used malone diimidate (II) is dihydrochloride, and tertiary amine. The preferable malone diimidate of the formula (II) is dimethyl malone diimidate.

EFFECT: new compounds feature useful biological properties.

6 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the new methylcetone pyrimidine -2 of the formula (I) and to the new method of their preparation. The compounds of the invention are intermediate products for synthesis of agronomical active effectors. The method of preparation of methylcetone pyrimidine -2 of general formula in which R1 and R2 define C1-C10 alkyl group in each case is that reaction malondiimidate of the general formula (II) , in which R1 has above mentioned value with β-ketoester of the general formula (III) , in which R2 has above mentioned value and R3 define C1-C10 alkyl group. Usually, water appeared during reaction are taken away from the reactor feed. Basic malondiimidate(II) can be derived in situ from the conforming salt and base. Preferably, used salt of malondiimidate (II) is dihydrochloride and used malondiimidate (II) is dimethylmalondiimidate. Preferably used β-ketoester (III) is acetacetic ester, 3-oxopentane ester.

EFFECT: method of the compound preparation is improved.

9 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new sulphamines with general formula (I) , where R1 represents (low) alkyl-O-(CH2)n-; R2 represents Ra-Y-(CH2)m-; R3 represents phenyl, which can be replaced by such substitutes as halogen, (low) alkyl or (low)alkoxy; R4 represents hydrogen; R6 represents hydrogen; X represents oxygen or a bond; Y represents a bond of -O-; n is equal to 2; m is equal to 2; Ra represents heteroaryl, in form of a 6-member aromatic ring, containing two nitrogen atoms, which can be substituted with such substitutes as halogen, thio(low)alkyl or (low)alkoxy; and their pharmaceutical salts. The invention also pertains to related objects, including the method of obtaining the following compounds formula II , formula III , formula IV , formula V , where radicals assume values indicated above or in the description.

EFFECT: invented compounds can be used as active ingredients for obtaining pharmaceutical compositions, which have inhibiting effect to endothelial receptors.

13 cl, 4 ex, 3 dwg, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing azoxystrobin by reacting a compound of formula (II): with 2-cyanophenol or a salt thereof in the presence of 2.5-40 mol. % 1,4-diazabicyclo[2,2,2]octane and an acid acceptor, where W is a methyl(E)-2-(3-methoxy)acrylate group C(CO2CH3)=CHOCH3. 1,4-diazabicyclo[2,2,2]octane is mixed with a compound of formula (II) only in the presence of 2-cyanophenol or when conditions are such that the compound of formula (II) and 1,4-diazabicyclo[2,2,2]octane are not capable of reacting with each other.

EFFECT: method enables to obtain a product with high output using a certain order of adding components.

12 c, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compositions having herbicidal activity, which contain a compound of formula (I) which is mixed with one or more known herbicide products, optionally stabilised by adding at least one inorganic or organic base, and the corresponding application for weed control in crops.

EFFECT: obtaining compositions having herbicidal activity.

20 cl, 1 tbl, 5 ex

Up!