The method of obtaining derivatives of propanolol acids and their stereoisomers

 

(57) Abstract:

The method of obtaining derivatives of propanolol acids and their stereoisomers. The essence of the invention: derivatives of propanolol acid of the formula: (Z - X) - C6H2-K-C6H3-C(COOCH3)=CHOCH3where is oxygen or sulfur, And is hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, hydroxy, phenoxy or C1-C4-alkylsulphonyl. Reagent 1: compound of formula (A, W, L)C6H3. Reagent 2: compound of formula (L, Y)C6H4where L, L - abseplyalamma group. 1 C. p., 1 C.p. f - crystals, 5 PL.

The invention relates to the field of acids, in particular to a method for producing derivatives of propanolol acid of General formula

and their stereoisomers, where A is hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, hydroxy, phenoxy or1-C4-alkylsulphonyl; It represents oxygen or sulfur; X IS O, S(O)n, NH, NR1: CH2, CHR2, CO, CH2CH2CH = CH, OCH2, (CH2)mO, CHR1O, OCH2O, S(O)nCH2, S(O)CH2O, NR1CH2, COO, OOC, SO2O COCH2O, COCHR1O, CONH, NHCO, NHSO2COS, SCO, N = N, CH2OCO, CH2SCO, CH2NHCO, CH2ON = CH2, OCH2<= CH, CH(OH), CO2CH2, SCH2O, NR1CO, S(O)2NH or CONR1; R1- C1-C4-alkyl; R2is phenyl; n is 0,1 or 2; m - 1,2,3,4, or 5; Q is a halide anion; Z is phenyl (possibly monosubstituted WITH1-C6-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, phenoxy,

by phenyl, amino, hydroxy, 1-(C1-C4-alkoxycarbonyl)-2-(C1-C4-alkoxy)-vinyl, WITH1-C4-haloalkoxy or1-C4-alkoxycarbonyl, or mono - or disubstituted by halogen, nitro, C1-C4-alkyl or cyano; naphthyl, chinoline, pyridinyl (possibly monosubstituted WITH1-C4-alkyl, C1-C4-alkoxycarbonyl, amino, halogen, nitro, C1-C4-alkylcarboxylic, di-(C1-C4-alkylsulfonyl)amino, or CH(O)NH, or mono - or disubstituted WITH1-C4-haloalkyl or cyano, or a disubstituted amino group and one from cyano, halogen or1-C4-alkoxygroup or disubstituted by nitro-group and one of cyano, halogen, di-(C1-C4-alkyl)amino or1-C4-alkoxygroup or substituted by cyano and two WITH1-C4-alkyl groups); pyrimidinyl (possibly: mono is tro, the phenyl, HO2C1-C4-alkoxycarbonyl or1-C4-alkylsulfonyl, or mono - or disubstituted WITH1-C4-alkoxy, or mono-, di - or tizamidine halogen, or disubstituted by halogen and one from C1-4alkyl or C1-4alkylthio, or disubstituted WITH1-4alkyl and C1-4haloalkyl), pyrazinyl (possibly monosubstituted by halogen or cyano, or disubstituted WITH1-C4-alkyl), pyridazinyl (possibly monosubstituted WITH1-C4-alkoxy, phenyl or aminocarbonyl, or mono - or disubstituted by halogen, or disubstituted by halogen and C1-C4-alkyl), benzothiazolyl, thienyl (possibly monosubstituted by pyrazolyl), which itself Disaese1-C4the alkyl and C1-C4-haloalkyl (or pyridinyl), which itself may monogamist nitro (or disubstituted by halogen), 1,2,4-triazolyl, honokalani (monosubstituted by halogen), 1,3,5-triazinyl (disubstituted by halogen, or disubstituted by halogen and C1-C4-alkoxy), thiazolyl (possibly monosubstituted nitro or mono-or disubstituted WITH1-C4-alkyl), benzoxazolyl, pyridinyl-N-oxide, thieno[2,3-d] pyrimidinyl, pyrrolyl (possibly mannose is l, pyrazolyl (substituted with halogen and two WITH1-C4-alkyl groups) or 1,2,4-triazinyl (monosubstituted with phenyl); provided that, when Z represents unsubstituted phenyl, and X and both represent oxygen, then A is not hydrogen; which possess fungicidal activity.

Known fungicides - MANCOZEB, carboxin, proxyfor. However, their activity is not high enough.

The aim of the invention is to develop a method of obtaining new compounds with fungicidal activity.

This goal is achieved by the proposed method of obtaining derivatives of propanolol acid of General formula I and their stereoisomers, the distinguishing feature of which is the fact that carry out interactions of compounds of the formula

with the compound of the formula

in the presence of a base, where one of L' and L" represents tsepliaeva group, while the other is a KN; W represents a ZX or group, which in turn ZX by:

(a) interaction in the presence of a base compound of the formula

H

(i) when X represents O, connection ZL; or

(ii) when X represents SO2O connection ZSO2
or (b) interaction in the presence of a base compound of the formula

LCH

(i) when X represents OCH2with connection ZOH; or

(ii) when X is a (C6H5)2P + CH2Q-and L represents a halogen, with a phosphine of the formula Z(C6H5)2P; or

(iii) when X represents CO.OCH2with connection ZCO.OH;

(C) when X represents CH = CH, interaction in the presence of a base compound of the formula

(RO)CH where R1represents a C1-C6-alkyl, with a compound of formula ZCHO; or

(d) when X represents CH = CH, the interaction of the compounds of formula (I), where X is a (C6H5)2P+CHR2Q-in series with the base and the carbonyl compound of the formula ZCHO; or

(e) when X represents CONH, interaction of the compounds of formula

in the presence of a base with a halogen acid of the formula ZCO.Q; or

(f) when X represents CH(OH), the interaction of the aldehyde of the formula

with a Grignard reagent of the formula ZMgHAI; or

(g) when X represents o, CO, interaction of the acid chloride of the formula

with the compound of the formula ZOH in padhee the compounds of formula

HOCH with the compound of the formula ZL; or

(j) when X represents N = N, the interaction formula

H with the compound of the formula ZN+= N Hal-; or

(k) when X represents NHSO2the interaction of the compounds of formula

ClSO with the compound of the formula ZNH2; where: A, B, E, X, K and Z have the meanings given above, L represents useplease group, preferably a halogen atom, and Q represents Hal; and Y represents a group CH3O. CH = C-(CO2CH3or half of CH2CO2CH3that can be converted into such a group by interacting with methylformate in the presence of a base and subsequent methylation in alkaline conditions.

Preferably the compounds of formula III

where Y' is a halogen, is subjected to the interaction with the phenol of General formula II

(II B) where A, X and Z have the above meanings, in the presence of a base, or salt of phenol (IIb) in the presence of a catalyst is a copper salt or mixture of salts of copper and metallic copper.

The invention is illustrated by the compounds listed in the following tables I, II, III and IV. Anywhere in the table.I, II, III and IV methyl-3-methoxypropionate the group has the (S)-configuration.

Table. 4 includes 320 compounds of the above General formula, where all values of Z, X, A, B, and E are shown in table.2, i.e. compounds NN 1-320 the same as in table.2, except for the values To that table.2 corresponds to the oxygen, and table.4 - sulphur.

In table.5 provides a proton NMR for some compounds of table. 1,2,3 and 4. Chemical shifts are denoted in mn-1from tetramethylsilane, in all cases, the solvent used deuterated chloroform. The column, entitled "frequency" refers to the operating frequency of the NMR spectrometers. In table.5 use the following abbreviations:

ush - broadened band

s - singlet

d - doublet

t - triplet

K - Quartet

m - multiplet.

The compounds of formula I are active fungicides and may be used against the following pathogens: Pyricularia oryzae on rice, Puccinia recondita, puscinis herdei and other rusts on barley, and plants. Erisiphe graminis (powdery mildew) on barley and wheat and other powdery mildew on various cultivated plants, such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), podosphaera feucolricha on apples and Uncinula necator on grapes Helminthosporium, Phynchosporium, Septoria, pseudocercosprella herepotrichoides and Caeumannomyces graminis on cereals. Cercospora arachidieda and cerasporidium personata on peanuts and other Cercospora species on other cultivated plants, for example sugar beet, bananas, soya beans and rice.

Botrytis cinerea (sulfuric powdery mildew) on tomatoes, strawberries, vegetables and other cultivated plants.

Alternaria on vegetables (e.g. cucumbers), rape, apples, tomatoes and other cultivated plants.

Vehtura inaegualis (scab) on apples.

Plasmopara vitocola on the grapes.

Other types of downy mildew, such as Bremia lactucae on lettuce, peronospora. - on soybeans, tobacco, onions and other cultivated plants, pseudoperounospora - hop and pseudoperonuspora cubeusis on the pumpkin. Phytophtora infestous - on potatoes and tomatoes, and other types of phytophtora - on vegetables, strawberries, avocado, pepper, ornamental plants, tobacco, cocoa and other cultivated plants. Thanatephorus cucumeris on rice and other Rhizoctonia species on various cultivated plants, such as wheat and the tee against fungi in vitro. Connections can also be active to diseases of fruits, coming after their harvesting (e.g., penicillium digitatum and italicum and Trichoderma viride on oranges, Gloesporium musarum on bananas and Botrytis cinerea on grapes).

In addition, individual connections can be active at potraviny seeds against fungi Fusarium species, Septeria Tilletia (solid head in the seeds of wheat). Ustilago, Helminthosporium on grain, Rhizochtonia solani on cotton and Pyriculare oryzae on rice.

Connections can be subjected to systematic promotion in plants. In addition, the compounds can be volatile enough to be active in the vapour phase against fungi on plants.

Many of the compounds of formula I, including those compounds in which X = 0, safer compared to cultivated plants (e.g., grapes), in comparison with the known ones by building connections.

Thus, it is proposed a method of combating fungi, which consists in applying to plants, plant seeds or the place where a plant or seed, an effective amount of compound according to the above definition or containing composition.

Connections can also be palchiki from fungal infestation of wood, tanned skin, skin products, and especially films of paint.

The compounds can be used as fungicides, but usually using a carrier or diluent based compounds receive the composition. Thus, offers a fungicidal composition comprising a compound of General formula I and fungicide acceptable carrier or diluent.

When used as fungicides compounds can be applied in a variety of ways. For example, they can be applied in the form of compositions and, as such, directly to the foliage of plants, seeds or habitat of plants or growing plants or can be applied by spraying, in the form of dust, cream or paste, in the form of vapor or granules with delayed action. The processing may be subjected to any part of the plant, including the leaves, trunk, branches or roots or the soil around the roots, or seeds before planting, or the soil in General, as well as water for irrigation or system aquaponic growing plants. Compounds of the invention can be in the form of injections introduced into plants or applied by spraying using techniques for electrodynamic spraying or other small-volume methods.

Connection is recommended for use in compositions for agricultural and horticultural purposes, and the type used in each case, the composition depends on the specific purpose.

The composition can be in the form testiruemi powders or granules containing the active ingredient (compound of the invention) and the solid carrier or diluent, such fillers like kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, mullerova earth, gypsum, diatomaceous earth and China clay. These granules can be pre-obtained pellets, suitable for use without additional processing. These granules can be prepared either by impregnation of the preformed carrier of the active component, either by pelletizing a mixture of the active ingredient and powdered media. Compositions for dressing seed may include means (e.g., mineral oil), facilitating the pouring of the composition in seeds. Or the active ingredient may be introduced into the composition for seed treatment use of an organic solvent (for example, N-methylpyrrolidone, propylenglycol, containing wetting or dispersing agent, contributing to the dispersion in the liquid. Powders and granules may also contain fillers and suspendresume tools.

Emulsifiable concentrates or emulsions can be prepared by dissolving the active component in an organic solvent may contain a wetting or emulsifying agent, and then adding the mixture to water which may also contain wetting or emulsifying agent. Acceptable organic solvents include aromatic solvents, such as alkyl benzenes and alkylnaphthalene, ketones such as isophorone, cyclohexanone, methylcyclohexanone, chlorinated hydrocarbons, such as chlorobenzene and dichloromethane, alcohols such as benzyl alcohol, furfuryl alcohol, butanol and simple glycol ethers.

Concentrated suspensions of nearly insoluble solid products can be prepared by grinding in a ball mill in the presence of dispersing funds with the inclusion of a suspending means, preventing the precipitation of the solid product.

Compositions intended for use in spraying, can be in the form of aerosols, ETANA or difenilamina.

The compounds of formula I can be mixed in the dry state with a pyrotechnic mixture with the formation of a composition suitable for the formation of a closed space smoke containing these compounds.

Or the same compound can be used in the form of microcapsules or can be incorporated with biodegradable polymers to achieve a slow controlled selection of the active substance.

The inclusion of appropriate additives, for example additives promoting distribution of the particles, increasing lipocell and resistance to rain on treated surfaces, i.e., different compositions may be better suited for different applications.

The compounds of formula I can be used in a mixture with fertilizers (e.g., nitrogen, potassium and phosphate). Recommended compositions containing only the fertilizer granules, including, for example, in the form of a coating compound of the invention. These granules preferably contain up to 25 wt. % of compounds of the invention. Thus, the invention provides a composition consisting of fertilizers and compounds of General formula I or its salts or its complex with the metal.

Wettable powders: Amul the EP wetting agent, dispersing agent, emulsifier or suspendisse tool. These substances can be cationic, anionic or non-ionic type.

Acceptable cationic surfactants are Quaternary ammonium compounds such as cetyltrimethylammonium bromide. Acceptable cationic surfactants include Soaps, salts of aliphatic monoamino sulfuric acid (for example, nutriceuticals), and salts of sulphonated aromatic compounds (for example, notredameuniversityi, sodium-, calcium - or moniliophthora, the mixture nutrivital and triisopropylphenylsulfonyl).

Acceptable non-ionic surfactants are the condensation products of ethylene oxide with fatty alcohols, such as alerby or cetyl alcohol, or with alkyl phenols such as octyl - or Nonylphenol and artilcles. Other nonionic surfactants can be called a partial esters formed by long-chain fatty acids, and anhydrides of exit, condensation products of these partial esters with ethylene oxide and lecithins. To an acceptable suspendium tools include hydrophilic colloids (e.g., the floor is so

Compositions intended for use in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate with a high content of active component such concentrates before use, dilute with water. These concentrates should preferably withstand long storage periods and after such storage must retain the ability to form aqueous preparations, which remain homogeneous for a sufficient time required for dispersion using the equipment for spraying. The concentrates generally contain up to 95%, preferably 10-85%, for example, 25-60 wt. % active component. After dilution with formation of an aqueous preparations obtained drugs can contain different amounts of active ingredient, depending on the intended use of the drug can be used in aqueous preparations containing 0,00055 or 0.01-10 wt.% the active component.

The composition can contain other biologically active compounds, for example compounds with similar or complementary fungicidal activity, or regulating the growth of plants, herbicide or insecticide activity.

The fungicidal compound, which may, under cereal crops (for example, wheat) caused by such pathogens as Septoria, Gibberella and Helminthosporium, contamination of seeds and contamination of soil, false, and powdery mildew on grapes, powdery mildew and scab on apples, etc. by including another fungicide composition acquires a broader spectrum of activity compared to using only one of the compounds of formula I. in Addition, another herbicide may have a synergistic effect on the fungicidal activity of the compounds of General formula I. Examples of fungicidal compounds which may be included in the composition of the invention include: carbendazim, benomyl, thiophanate-methyl, thiabendazole, fuberidazole, etridiazole, dichlofluanid, having cymoxanil, oxadixyl, operas, metalaxyl, parallaxis, benalaxyl, fosetyl-aluminum, fenarimol, iprodione, protocorm, procymidon, vinclozolin, penconazole, myclobutanil, propamocarb, diniconazole, pyrazophos, ethirimol, datalists, tridemorph, triforine, nuarimol, triazolyl, guazatine, triacetate salt of 1,1'-iminodi(octamethylene)biguanidine, butiaba, propiconazol, prochloraz, flutriafol, hexaconazole, (2RS, 5RS)-5-(2,4-dichlorophenyl)tetrahydro-5-(1H-1,2,4-triazole-1-ylmethyl)- 2-furyl-2,2,2-triptoreline ether, tsyprokonazolu, tebuconazol, 1-[(2P, 4P; 2RS; 4RS)-4-bromo-2-the n-7 - carboxylic acid, 3-(2,4-dichlorophenyl)-2-(1H, 1,2,4-triazole-1-yl)hinzelin-4-(3H)-it, (RS)-1-aminopropylphosphonic acid, flusilazol, triadimefon, triadimenol, diclobutrazol, fenpropimorph, pirivenas, fenpropidin, CHLOROTHALONIL, imazalil, fanforum, carboxin, oxycarboxin, mefenoxam, dodemont, BAS 454, blasticidin S, kasugamycin, edifenphos, kitazin P, cycloheximide, phtalic, provenzal, isoprothiolane, tricyclazole, 4-chloro-N-(cyano(ethoxy)methyl)benzamide, pyroxylin, chlorobenzene, paasonen, polyoxin D, validamycin A, mepronil, flutolanil, pencycuron, dilamtin, fenesin-oxide, nickeldimethylglyoxime, technicall, bitertanol, bupirimate, itaconate, hydroxyethoxy, streptomycin, zipform, bisoxazole, chinomethionat, dimethirimol, 1-(2-cyano-2-methoxyimino)-3-utilmately, verapamil, tolliametile, proxyfor, polishers, MANEB, MANCOZEB, captafol, CHLOROTHALONIL, anilazine, thiram, Captan, folpet, zineb, propineb, sulfur, dinocap, Dylan, chloroneb, bankroll, nitratenitrogen, Dodin, dithianon, pentahydroxy, fentiazac, Tecnatom, hintzen, dichloran, copper compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, and organomercury compounds.

Compounds of General formula I can the surrounding soil or foliage fungal infections.

Acceptable insecticides that can be included in the composition of the invention include: pirimicarb, dimethoate, Demyansk.-methyl, formation, carbaryl, isoprocarb, CMS, PMS, carbofuran, carbosulfan, diazinon, fenthion, fenitrothion, pentat, chlorpyrifos, isoxathion, propafol, monocrotophos, buprofezin, retroposition, cicloprofen.

To regulate the growth of plants compounds include compounds that regulate the formation of weeds or germination, or selectively regulating the growth of less desirable vegetation (e.g. grass).

Examples of acceptable for use together with the compounds of formula I of the plant growth regulators include: gibellini (for example, HA3GA4or HA7), the auxins (e.g. introcaso acid, indomalaya acid, naftoxinon acid or naphthyloxy acid), the cytokinins (e.g. kinetic, diphenylacetone, benzimidazole, benzyladenine or benzylaminopurine), venexiana acid (for example, 2,4-D or MHPC), substituted benzoic acids (e.g., triiodobenzoic acid), morphactin (for example, chlorfluazuron), hydrazide maleic acid, glyphosate, glitsin, long chain fatty alcohols and acids, dikegulac, Pablo chlormequat chlorophonia or mercatoria), ethephon, carbetamide, methyl-3,6-dichloracetate, daminozide, sultam, abscisic acid, isoperibol, 1-(4-chlorophenyl)-4,6-dimethyl-2-oxo-1,2-dihydropyri-Dean-3-carboxylic acid, hydroxybenzonitrile (for example, bromoxynil), difenzoquat, benzoylpropionic-3,6-dichlorphenol acid, fenbendazol, invented, thiapentanal and tecnazene.

The following examples are given to illustrate the invention. In all examples, the term "ether" refers to diethyl ether, drying of the solutions apply magnesium sulfate, the solution concentrated under reduced pressure. Reactions involving moisture sensitive intermediates is carried out in nitrogen atmosphere and solvents before use dried where necessary. Unless otherwise specified, chromatography is performed on filled with silica gel column. Where indicated, data infrared and NMR spectroscopy selective without specifying in all cases, all of the absorption bands.1H-NMR spectra were recorded using as solvent CDCl3if no special instructions. Everywhere use the following abbreviations:

DME - dimethoxyethane, THF is tetrahydrofuran, DMF is N,N-dimethylformamide, NMR - nuclear magnetic resonance, infrared infrakrasnoaya

TLC = thin layer chromatography

HPLC = high performance liquid chromatography

Br = broad

ppm = millionths.

The invention is illustrated by the following examples.

P R I m e R 1. This example illustrates how to obtain (E)-methyl 2-[2-(3-benzyloxyphenyl)phenyl]-3-methoxypropionate (compound N-23, PL.1).

A mixture of 100 g (0.54 mol) of 2-bromobenzaldehyde, 67,03 g (1,08 mol) of ethylene glycol, 0.5 g toluensulfonate acid and toluene was heated to boiling point and kept at this temperature under reflux for 6 hours during this time was 23 ml distilled azeotropic mixture of water and ethylene glycol. After that, the mixture was cooled and added to 1 l of ether. The ether solution was washed with saturated sodium bicarbonate solution (200 ml), then three times with water, portions of 150 ml and finally, 150 ml of a saturated solution of sodium chloride. After drying and filtration and then evaporation of the ethereal solution was obtained 121,96 g (yield to 98.6%) of 2-(2-bromophenyl)-1,3-dioxolane in the form of an oily liquid.

1H NMR: (60 MHz): 3,4 (4H, m) 6,0 (1H, s), 6,9-7,6 (4H, m), M. D.

The product received without additional purification was used in the next stage.

aboutAnd added to it 120 g (0,524 mol) of 2-(2-bromophenyl-1,3-dioxane, 200 ml of TMP and 0.2 g of copper chloride. The mixture was slowly heated to 150-155aboutWith and drove toluene. Then it was kept for 6 hours at 150-155aboutC, and then cooled to 25aboutWith and added 500 ml of water. The mixture was filtered, the residue washed with 200 ml of ether, and the filter was subjected to extraction with ether (three times, portions 150 ml). The combined ether phases are washed twice with 2 n sodium hydroxide solution, (portions 150 ml), and four times with water (portions 150 ml) and then 150 ml of brine. After drying and filtration, the ether solution was evaporated, receiving the result of 124.1 g (yield 87,1%) 2-[2-(3-methoxyphenoxy)phenyl]-1,3-dioxolane in the form of an oily liquid.

1H NMR: (60 MHz): the 3.65 (3H, s), of 3.95 (4H, d), 6,12 (1H, s), and 6.6 and 7.6 (8H, m) M. D.

The product received without additional purification was used in the next stage.

32.7 g (0.12 moles) of 2-[2-(3-methoxyphenoxy)phenyl]-1,3-dioxolane was stirred in a mixture of 95 ml of water and 5 ml of concentrated hydrochloric acid at the temperature of the environment was washed with 30 ml of saturated aqueous sodium bicarbonate solution, three times with water (30 ml) and, finally, 30 ml of brine. The resulting solution was dried, filtered and concentrated, resulting in the 26,17 g (yield of 95.4%) rather pure 2-(3-methoxyphenoxy)-benzaldehyde (A) as oily liquid. The product received without additional purification was used in the next stage. A sample for analysis, however, was prepared using chromatography, using as eluent a mixture of ether and hexane. The result obtained oily liquid amber.

1H NMR: (90 MHz): with 3.79 (3H, s), 6,58-7,97 (8H, m), 10,49 (1H, d) M. D.

IRmax(film): 1691, 1599 cm-1.

A mixture of 25.0 g (0,109 mol) of 2-(3-methoxyphenoxy)-benzaldehyde, 13,64 g (0.11 mol) of methyl-maritimerelated, 8,0 ml of 30% aqueous hydroxide solution designed in methanol and 150 ml of THF was stirred for 45 minutes at boiling temperature under reflux. The resulting solution was evaporated to dryness and the residue was subjected to chromatography using as eluent a mixture of ether and hexane. The result has been 27,67 g (75,3% yield) sulfoxide (B) resin amber color.

1H NMR: (60 MHz): 2,2 (3H, s) to 2.55 (3H, s), the 3.65 (3H, s), 6,35-8,15 (N, m) M. D.

20 ml AC keeping the temperature 20-25aboutC. Then, to the mixture was added at once a solution 27,67 g (0.83 mol sulfoxide (B) and 40 ml of methanol and the resulting solution was stirred at ambient temperature for 18 hours the Methanol solution was evaporated to dryness under reduced pressure and the residue (22,78 g of a brown resin) was dissolved in 200 ml of ether. The ether solution was washed with saturated aqueous sodium bicarbonate solution, was filtered small number of nerastvorimogo material and evaporated to dryness. The residue was subjected to chromatography using as eluent a mixture of ether and hexane. The result has been 15.62 wide g (yield of 69.3%) of 2-(3-methoxyphenoxy)-phenylacetate (S) in the form of a viscous oily liquid.

12,89 g (0,051 mol) tribromide boron was dissolved in 50 ml dichloromethane and the resulting solution was cooled to 0-5aboutWith, after which was added to it dropwise within one hour, with stirring, a solution of 7.0 g (0,026 mol) of 2-(3-methoxyphenoxy)-phenylacetate in 80 ml of dichloromethane. After stirring for 20 min at 0-5aboutTo the mixture was added dropwise, with stirring, to 100 ml of absolute methanol, maintaining the temperature between 0-5aboutC. the Resulting solution was poured into 250 ml of water with dissolved 12 g of sodium bicarbonate and the mixture rayed what about the sodium chloride solution. After drying, filtration and evaporation was received 6,12 g (yield 92,3%) of methyl 2-(3-oxygenase)-phenylacetate (D) in the form of a brown resin. The product received without additional purification can be used in the next stage. Using chromatography using as eluent a mixture of ether and hexane, however, received a high-purity product in the form of a viscous Golden oily liquid, which quickly darkened upon exposure to air.

Besides the above, methyl-2-(3-oxygenase)-phenylacetate (D) was obtained in the following way.

A mixture of 30 g (0.18 mol) of 2-chlorophenylalanine acid, 48.6 g (0.34 mol) of potassium carbonate and 43.5 (0.35 mol) of 3-methoxyphenol was heated with stirring at 140aboutIn the presence of catalytic amount of copper chloride (I). After 3 h according to the gas and thin-layer chromatography of the original acid is completely reacted. The reaction mixture was allowed to cool down (adding thereto 5 ml of dry DMF), 70aboutWith that it does not become too viscous, then poured in water and acidified with hydrochloric acid. The resulting mixture was subjected to extraction with ether, the combined ether phases are washed with water until neutral, dried and evaporated, resulting in resultslist fluid, which without further purification was used in the next stage.

Brown oily liquid was boiled for 2.5 h under reflux in 70 ml of methanol with the addition of 2 ml of concentrated sulfuric acid. The reaction mixture was then cooled to room temperature and poured into water. The resulting mixture was twice subjected to extraction with ether, the ether phases were combined, washed first with diluted aqueous sodium hydroxide solution and then with water until neutral and dried. After evaporation got to 34.9 g of crude methyl 2-(3-methoxyphenoxy)-phenylacetate as an orange-brown oily liquid (the content of the target product, determined by gas chromatography, was equal to 86%). The resulting crude product was combined with another batch (8,2 g) of the same product obtained by the same method. After repeated molecular distillation (50-150aboutC at a pressure of 4 x 10-2Mbar) received by 37.1 g of purified (purity 95%, the yield of about 60% based on 2-chlorophenylalanine acid) methyl-2-(3-methoxyphenoxy)-phenylacetate. By repeating the above operations, received the right amount of product.

97 g (0.36 mol) of methyl 2-(3-methoxyphenoxy)-phenylacetate of islote. The mixture was left to stand overnight at room temperature, then added to it 100 ml of concentrated Hydrobromic acid and again heated to 110aboutC. After holding the reaction mixture at this temperature for 7 h all the source material reacts. The reaction mixture was cooled to room temperature, poured into brine and was extracted twice with dichloromethane. After distillation of dichloromethane was obtained oily liquid, which was heated at 70aboutWith 400 ml of methanol and 2 ml of concentrated sulfuric acid for 2 h, the Reaction mixture was then cooled to room temperature, poured into brine and was extracted twice with dichloromethane. The combined extracts were washed with water until neutral, dried, filtered and evaporated, receiving of 92.8 g of brown oily liquid. After molecular distillation (150aboutC and a pressure of 1 x 10-3Mbar) of product (72,8 g) received 41,4 g (yield 57%, based on methyl-2-(3-methoxyphenoxy)-phenylacetate) methyl-2-(3-oxygenase)-phenylacetate (D) in the form of Golden syrup.

1H NMR: (60 MHz): only 3.57 (3H, s), 3,63 (2H, s), of 5.82 (1H, s), from 6.4 to 7.35 (8H, m) M. D.

IRmax(film): 3408, 1713 cm-1.

To aspenleaf (D) in 10 ml of DMF and 10 g (0,167 mol) of methylformate. After stirring for 45 min, to the mixture was added 100 ml of water and extraction was performed with 50 ml of ether. The aqueous layer was acidified with hydrochloric acid to pH 3-4 and the mixture was twice subjected to extraction with ether (40 ml). The combined ether extracts are washed three times with water (30 ml), and then 30 ml of a saturated solution of sodium chloride and dried. Ether drove away, and the residue was dissolved in 20 ml of DMF and added to a solution of 0.64 g (0,0046 mol) of anhydrous potassium carbonate and 0.55 g (0,0044 mol) dimethylsulfate. The mixture was stirred at ambient temperature for one hour, after which were added thereto 100 ml of water and twice subjected to extraction with ether (40 ml). The combined ether extracts are washed three times with water (20 ml), and then 20 ml of saturated sodium chloride solution, dried, filtered, evaporated to dryness and then subjected to chromatography using as eluent a mixture of ether and hexane. The result was obtained (E)-methyl 2-/2-(3-oxygenase)phenyl/-3-methoxypropane (E) resin amber color. After rubbing it with a mixture of hexane and dichloromethane were obtained 0.7 g (yield 30%, based on methyl-2-(3-oxygenase)-phenylacetate (D)) of a white solid. The melting point of 115.

A solution of 12 g (0,0465 mol) of methyl 2-(3-oxygenase)phenylacetate (D) and 55.8 g (of 0.93 mol) of methylformate in 35 ml of DMF was added dropwise over 45 min to a stirred suspension of sodium hydride (6,696 g of a 50% dispersion in oil, 0,1395 mol, pre-washed with petroleum ether 40-60) in 65 ml of DMF. The reaction mixture was stirred at room temperature for 2.5 h, then poured into 200 ml of water, acidified to pH 3 with concentrated hydrochloric acid and then twice subjected to extraction with ether (portions of 200 ml).

The combined organic extracts were twice washed with brine (portions of 200 ml), dried, filtered and evaporated, to deliver 12,5 (0,0433 mol) of a yellow oily liquid.

12.5 g (0,0433 mol) of the obtained oily residue was dissolved in 100 ml of DMF and added to a solution 5,98 g (0,0433 mol) of sodium carbonate. After stirring for 10 min to the mixture at once added 5,19 g (0,042 mol) dimethylsulfate in 10 ml of DMF. The resulting mixture was stirred over night at room temperature, poured into 200 ml of water and subjected to extraction with ether (twice with portions of 200 ml). The combined ether extracts are washed three times with brine (portions of 200 ml), dried, filtered and evaporated, Poluchenie)phenyl] -2-me-oxypropane (E). So pl. 117-118aboutC.

1H NMR (90 MHz): to 3.58 (3H, in), 3.75 (3H, s) 5,38 (1H, s), 6,39-7,33 (8H, m), and 7.4 (1H, s) M. D.

IRmax. (nujol): 3295, 1672, 1630 cm-1.

A mixture of 1.0 g (0,0033 mol) of (E)-methyl 2-[2-(3-oxygenase)phenyl]-3-methoxypropionate, 0,57 g (0,0033 mol) of benzylbromide, 0.8 g (0,0053 mol) of potassium carbonate and 15 ml of dry DMF was stirred for 3 h at ambient temperature. Then to the mixture was added 50 ml of water and twice subjected to the extraction with ether (30 ml). The combined organic extracts were twice washed with water (20 ml) and after drying and filtering, the ether solution was evaporated to dryness and subjected to chromatography, using as eluent a mixture of ether and hexane. The result has been a 1.11 g (yield 85%) of target compound (F) in the form of a colourless resin.

1H NMR: (90 MHz): 3,55 (3H, s), and 3.7 (3H, s), equal to 4.97 (2H, s), 6.5 to 7,32 (13H, m), 7,44 (1H, s) M. D.

IRmax(film): 1710, 1638 cm-1.

P R I m m e R 2. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-phenylsulfonylacetate) -phenyl]- propanoate (compound No. 51 of the table.1).

A mixture of 0.5 g (0,00166 mol) of (E)-methyl 2-[2-(3-oxygenase)phenyl]-3-methoxypropionate obtained by using method,0aboutC. After this mixture was cooled to 25aboutWith that added to it 60 ml of water and twice subjected to extraction with ether (30 ml). The combined ether extracts were washed with 20 ml water, 20 ml of diluted hydrochloric acid, three times with water (portions of 200 ml) and 20 ml of saturated solution of sodium chloride. The ether solution was dried, filtered, concentrated and subjected to chromatography, using as eluent a mixture of chloroform and hexane. The result was obtained 0.21 g (yield of 28.7%) of target compound in the form of a colourless resin.

1H NMR (90 MHz): of 3.56 (3H, in), 3.75 (3H, s), 6,52-of 7.96 (13H, m), 7,40 (1H, s) M. D.

P R I m e R 3. This example illustrates how to obtain (E)-methyl 3-methoxy-2-{ 2-[3-(4-nitrophenoxy)phenoxy]phenyl}- propanoate (compound N 133 of the table.1).

A mixture of 1.2 g (0,004 mol) of S-methyl-2-[2-(3-oxygenase)phenyl]-3-methoxypropionate, obtained as described in example 1 by way of 0.68 g (0,008 mol) of potassium carbonate and 15 ml of DMF was stirred for 16 h at ambient temperature, then poured the mixture into water (80 ml) and was twice subjected to the extraction with ether (30 ml). The combined organic extracts washed three times with water (25 ml), and then 25 ml of a saturated solution of sodium chloride. After that, their weforma and hexane. The result was received with 0.93 g (yield of 55.2%) of target compound.

1H NMR: (90 MHz): 3,55 (3H, s), and 3.72 (3H, s), 6,67-to 8.41 (N, m), 7,44 (1H, s) M. D.

P R I m e R 4. This example illustrates how to obtain (E)-methyl-2-{2-[3-(4-pertenece)phenoxy] phenyl}-3-methoxy-propenoate (compound N 124 table.1).

A mixture of 1.0 (0,0033 mol) of (E)-methyl 2-/2-(3-oxygenase)phenyl/-3-methoxypropionate, obtained as described in example 1 by the way, 2,63 g (0,0069 mol) of bis-4-(forfinal)iodinebased, 0.5 ml of triethylamine, 0.5 g of copper powder and 15 ml of absolute methanol was boiled for 6 hours under reflux. After this was added to a mixture of 1 g (4-forfinal)iodinebased and boiled her under reflux for another 3 hours After cooling and filtration, to the filtrate was added 80 ml of water and the mixture was twice subjected to extraction with ether (30 ml). The combined ether extracts are washed three times with water (portions 15 ml), and then 15 ml of a saturated solution of sodium chloride.

After drying and filtration, the ether solution was concentrated, resulting in the 0.16 g (yield of 12.3%) of target compound in the form of resin amber color.

1H NMR: (60 MHz): 3,42 (3H, s), 3,51 (3H, s), 6,35-7,30 (N, m), 7,35 (1H, s) M. D.

IRmA inputs3-benzoylacetonate)phenyl] -3-methoxypropionate (compound No. 49 of the table. 1).

A mixture of 0.5 g (0,00166 mol) of (E)-methyl 2-[2-(3-oxygenase)-phenyl]-3-methoxypropionate, obtained as described in example 1 by the way, 0.26 g (0,00185 mol) of benzoyl chloride, to 0.23 g (0,00166 mol) of potassium carbonate and 10 ml of DMF was stirred for 1.5 h at ambient temperature. Then to the mixture was added 0.26 g (0,00166 mol) of benzoyl chloride and 0.23 g (0,00166 mol) of potassium carbonate and continued stirring under the same conditions for a further 16 hours and Then thereto was added 80 ml of water and twice subjected to extraction with ether (40 ml). The combined ether extracts are washed three times with water (20 ml water and 20 ml saturated sodium chloride solution, then dried, filtered, concentrated and subjected to chromatography, using as eluent a mixture of ether and hexane. The result has been more than solid. After another recrystallization from aqueous methanol was received to 0.23 g (yield of 47.7%) of the pure target compound as a white solid. So pl. 94-95aboutC.

1H NMR: (90 MHz): 3,62 (3H, s), 3,74 (3H, s), 6,76 is 8.38 (13H, m), 7,46 (1H, s) M. D.

IRmax. (nujol): 1741, 1627 cm-1.

P R I m e R 6. This example illustrates how to obtain (e,E)-methyl-2-{ 2-[3-(4-chlorophenolate)-4-o 6,64 ml of 0.25 M aqueous solution of 3-chlorantraniliprole and the mixture was cooled to a temperature below 10aboutC. Then, thereto was added dropwise 3,32 ml of 0.5 M aqueous solution of sodium nitrite and stirred for 10 min at a temperature below 10aboutC. the Resulting solution of chloride of 3-flordiasociety was added dropwise with stirring to a mixture of 0.5 g (0,00166 mol) of (E)-methyl 2-[2-(4-oxygenase)phenyl]-3-methoxypropionate obtained in the same manner as described in example 1 for the corresponding 3-hydroxy-derivative, in 16 ml of 0.1 M aqueous solution of sodium hydroxide and 30 ml of acetone. At the same time continued to add sodium hydroxide solution to maintain a pH in the range 8-10, keeping the temperature below 10aboutC. After stirring for 20 min the mixture was twice subjected to extraction with ether (40 ml). The combined ether extracts are washed three times with water (portions 15 ml), and then 15 ml of a saturated solution of sodium chloride, after which they were dried, filtered, concentrated and subjected to chromatography, using as eluent a mixture of ether and hexane. The result has been a solid orange color. After recrystallization it from a mixture of hexane and dichloromethane were obtained 99,3 mg (yield of 13.6%) of the pure target compound; so pl. 143-144aboutC.

P R I m e R 7. This example C of table.1).

To a stirred solution of 0.61 g of sodium in 10 ml of methanol was added at once 4,34 g resorcinol. After stirring the resulting mixture for half an hour at room temperature the excess methanol drove away under reduced pressure. To the residue in the form of an oily liquid color orange was added 6.6 ml of pyridine, 14,74 g 3-bromoanisole and 192 mg of copper chloride. The mixture was stirred for 66 h at 125aboutC, then cooled and poured into diluted hydrochloric acid, and then subjected to extraction with ether. The ether extracts were subjected to Stripping of dilute aqueous solution of sodium hydroxide. Aqueous extracts were acidified with diluted hydrochloric acid and subjected to extraction with ether. The obtained ether extracts were washed successively with water and brine, and then dried and concentrated, to deliver and 3.72 g of oily liquid red. After distillation of this liquid (oven temperature 170aboutWith a pressure of 0.05 mm RT.CT.) received 1,71 g of 3-(3-methoxyphenoxy)-phenol in the form of a thick oily liquid, pale yellow.

1H NMR, : of 3.78 (3H, s), is 4.93 (1H, s) M. D.

To a stirred solution of 0.18 g of sodium in 4 ml of methanol was added at once 1.70 g of 3-(3-labels is OK methanol drove away under reduced pressure. To the residue in the form of an oily liquid color orange was added to 0.85 g o-bromoferrocene acid and 40 mg of copper chloride and the reaction mixture was stirred for one hour at 130aboutC. thereafter, thereto was added 0.4 g of o-bromoferrocene acid and 0.13 g of ethoxide sodium and continued stirring at 130aboutC for another 3 hours

The mixture is then cooled, acidified with diluted hydrochloric acid and subjected to extraction with ether. The ether extracts were washed successively with water and brine, then dried and concentrated, obtaining the result of 3.12 g of oily liquid red, containing 2-[3-(3-methoxyphenoxy)phenoxy]-phenyloxy-ing the acid. To 3.12 g of this acid was added 40 g of methanol and 3 drops of concentrated sulfuric acid. The reaction mixture was stirred for one hour at 90aboutC, then slowly cooled, poured into water and subjected to extraction with ether. The ether extracts were washed successively with diluted aqueous sodium hydroxide solution, water and brine, dried and concentrated, obtaining the result of 1.33 g of oily liquid yellow. After distillation (oven temperature 160aboutWith the pressure of 0.07 mm RT.CT.) received of 1.03 g (yield 36%) in the calculation (2H, C) of 3.78 (3H, s) M. D.

A mixture of 1.00 g of methyl-[3-(3-methoxyphenoxy)phenoxy]-phenylacetate and 3,34 ml methylformate in 1 ml DMF was added dropwise over 10 min and stirred suspension of 0.13 g of sodium hydride in 10 ml of DMF, cooled with ice to a temperature below 10about(This was accompanied by the liberation of gas bubbles). After the addition was finished the reaction mixture was stirred for 2 h at room temperature, then poured into water, acidified with diluted hydrochloric acid and subjected to extraction with ether. The extracts were washed with water, dried and concentrated, resulting in the 1,09 g yellow oily liquid. To a stirred solution of this liquid in 20 ml of DMF was added 0,76 g of potassium carbonate and 0.33 g of dimethylsulfate and the resulting mixture was stirred at room temperature for 2.5 h, then poured in water and subjected to extraction with ether. The extracts were washed with water, dried, concentrated and subjected to chromatography, using as eluent a mixture of ether and petrol (1:1). The result has been to 0.61 g (yield 55%, based on methyl-2-[3-(3-methoxyphenoxy)phenoxy]-phenylacetate target compound as a colorless viscous oily liquid.

1H NMR, : of 3.60 (3H, in), 3.75 (3H, s), ptx2">

P R I m e R 8. This example illustrates how to obtain (E)-methyl 3-methoxy-2-{ 2-[3-(phenoxymethyl)phenoxy]phenyl}-Pro-Pinout (compound No. 21 of table.1).

0.50 g (E)-methyl 3-methoxy-2-[2-(3-methylphenoxy)phenyl] -propanoate obtained from 3-METHYLPHENOL and 2-bromobenzaldehyde described in example 1 way, and 0.30 g of N-bromosuccinimide boiled under reflux in 25 ml of carbon tetrachloride with traces of azobisisobutyronitrile (AIBN) within 4.5 hours, adding every 1.5 h traces of AIBN. The reaction course was monitored by gas chromatography. Then the reaction mixture was left to stand overnight at room temperature, was added a trace amount of AIBN and continued to boil it up until gas chromatography showed almost complete absence of starting material (1 h). Then the reaction mixture was filtered through celite, washed with water and evaporated, getting to 0.69 g of a pale yellow resin. According to gas chromatography and NMR, this resin consisted of (E)-methyl 2-[2-(3-bromomethylphenyl)phenyl]- 3-methoxypropionate (80% ), corresponding dibromochloro derivative (11%) and unreacted starting material (propenoate, 8%).

1H NMR data for the main component additional purification.

Part of this crude material (0,42 g, concentration of 80%) was mixed with 0,105 g of phenol and 0,077 g of potassium carbonate in 20 ml of DMF and heated for one hour at 60aboutC. Then the mixture was left overnight at room temperature, then was heated at 60aboutC for another hour, cooled, poured into water and subjected to extraction with ethyl acetate. The organic fraction was washed with water, dried and evaporated, resulting in the 0,42 g of pale yellow oily liquid. After purification using high performance liquid chromatography using as eluent a mixture of gasoline and ethyl acetate, taken in the ratio of 3:1, was received with 0.13 g of the target compound as a colourless resin containing as an impurity 20% (E)-methyl 2-[2-(3-dibromoethylene)phenyl]-3-methoxypropionate.

1H NMR data for the target connection: : to 3.58 (3H, s), 3,70 (3H, s), to 4.98 (2H, s), 6,88 and 7.36 (C), (13H, m), 7,46 (1H, s). M. D.

P R I m e R 9. This example illustrates how to obtain (E) methyl-2-[2-(2-acetyl-5-phenoxyphenoxy)phenyl] -3-methoxypropionate and (E)-methyl 2-/2-(4-acetyl-3-phenoxyphenoxy)phenyl/-3-methoxypropionate (compound N 366 and 365, respectively, of the table.1).

Methyl-2-(3-phenoxyphenoxy)phenylace - tat was obtained from 3-phenoxy)phenylacetate. The product received is translated into (E)-methyl 3-methoxy-2-[2-(3-phenoxyphenol-si)phenyl]-propanoate (1H NMR (250 MHz) 3,61 (3H, s), of 3.78 (3H, s), 6,68-to 7.35 (13H, m), of 7.48 (1H, s) m,D.) using sodium hydride and methylformate, and then potassium carbonate and dimethylsulfate, according to the method described in example 1, to obtain (E)-methyl 2-[2-(3-oxygenase)phenyl] -3-methoxypropionate, with the difference that in this case used two equivalents of sodium hydride.

To mix the solution 0,722 g (1.92 mmol) of (E)-methyl 3-methoxy-2-/2-(3-phenoxyphenoxy)phenyl/propanoate in 20 ml of dry dichloromethane was added at 0-5aboutWith 0,512 g (of 3.84 mmol) of powdered aluminium chloride and then added dropwise within 10 min, the solution 0,151 g (1.92 mmol) of acetylchloride in 3 ml of dry dichloromethane. The resulting mixture was stirred overnight and allowed to warm to ambient temperature. The reaction mixture was then diluted with 125 ml of ether, washed twice 2n. hydrochloric acid, 10% aqueous solution of sodium carbonate and finally with water. The residue obtained after distillation of the solvent was subjected to purification via flash chromatography, using as eluent a mixture of ether and petrol. The result has been 0,424 g of a mixture of the two target compounds in the approximate ratio of 3 is using high-performance liquid chromatography on silica gel, using as eluent a mixture of hexane, dichloromethane and methyl tert-butyl ether with a mixing ratio of 70: 25:5. The result has been (I) regioisomer A (0,179 g), along with the first and which is the main component of the mixture in the form of a white crystalline substance. So pl. 90-92aboutC.

1H NMR, (250 MHz): 2,52 (3H, s), of 3.56 (3H, s), and 3.72 (3H, s), 6.48 in (1H, d), only 6.64 (1H, HF), 6,9-7,4 (N, m), the 7.43 (1H, s), to 7.84 (1H, d) M. D. and (II) regioisomer B (0,061 g, mixed with about 5% of regioisomer A) coming second and contained in the mixture in a smaller number, in the form of a white crystalline substance; so pl. 82-85aboutC.

1H NMR (250 MHz): of 2.51 (3H, s), 3,60 (3H, in), 3.75 (3H, s), of 6.45 (1H, d), 6,59 (1H, HF), 6,9-7,4 (N, m) of 7.48 (1H, s), 7,82 (1H, d) M. D.

P R I m e R 10. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-pyrimidine-2-yl-oxygenase)phenyl] propenoate (compound No. 22 of table.2).

A mixture of 0.5 g of (E)-methyl 2-[2-(3-oxygenase)phenyl]-3-methoxypropionate, obtained as described in example 1 way, and 0.46 g of potassium carbonate, to 0.23 g of 2-chloropyrimidine and 0.01 g of copper chloride in 15 ml of DMF was heated for 4 h under reflux. After cooling, the mixture was poured into water and filtered. The filtrate was subjected to extraction with ether. The combined ether ei, using as eluent a mixture of ether and hexane. The result has been 0,26 (yield 41% ) of target compound, IR (film): 1707, 1633 cm-1.

1H NMR (90 MHz): of 3.54 (3H, s), 3,68 (3H, s), 6,74-7,34 (N, m), 7,38 (1H, s), of 8.28 (2H, d) M. D.

P R I m e R 11. This example describes how to obtain (E)-methyl 3-methoxy-2-[2-(3-phenoxyphenyl)phenyl]propenoate (compound N 446 table.3).

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2-Mercaptophenylacetic acid has been described in the literature (see D. Papa, etc., J. Org.Chem. 1949, 24.723, R. H. Glauert, F. G. Mann, J. Chem. Soc. 1952, 2127 and references in this article). 1.68 g of 2-mercaptophenylacetic acid was added to a mixed solution of 0.8 g of sodium hydroxide in 10 ml of methanol (compare D, C. Atkinson and others J. Med.Chem., 1983, 26, 1361). The resulting orange solution was stirred at room temperature for 90 min, then concentrated under reduced pressure, removing the remains of methanol by azeotropic distillation with toluene. The result was a yellow solid. To a stirred solution of this yellow substance in 20 ml of DMF was added 0.2 g of copper chloride and the solution 2,49 g 3-phenoxypropanol obtained from 3-phenoxyphenol and triphenylphosphine according to the method described by J. P. Schaefer and other Org.Synth., Coll, T. 5, 142) in 10 ml of DMF. The resulting mixture was heated Barely cooling the reaction mixture was poured into aqueous sodium hydroxide solution and three times washed with ether. The aqueous solution was acidified with concentrated hydrochloric acid and three times was subjected to extraction with ether.

The extracts were washed with water, dried and concentrated, to deliver 2.2 g oily liquid Magenta, consisting mainly of 2-(3-phenoxyphenyl)-phenylacetic acid. The solution of this oily liquid in 20 ml of methanol was added to the acidic methanol, obtained by careful treatment 30 ml of methanol and 3.5 ml of acetylchloride, and the resulting mixture was stirred for 90 min at room temperature. The reaction mixture was then concentrated and the residue was distributed between ether and aqueous sodium bicarbonate solution. The organic layer was separated and washed sequentially with an aqueous solution of sodium hydroxide (twice) and three times with water, then dried and concentrated, obtaining the result of 2.06 g of crude 2-(3-phenoxyphenyl)phenylacetate in the form of an oily liquid purple.

IRmax. (film): 1740 cm-1with a purity of 94% (determined by gas chromatography). Crude methyl 2-(3-phenoxyphenyl)-phenylacetate translated in the target connection with the release of 53% in two stages, in the same manner as described in example 7 to translate meat, namely, by forming methylformate and sodium hydride and subsequent O-methylation by dimethylsulfate and potassium carbonate. The resulting product was an orange resin (degree of purity, determined by gas chromatography, 98%), which crystallized upon standing. So pl. 48-51,5aboutC.

IRmax. (film): 1710 and 1632 cm-1.

1H NMR (270 MHz): 3,62 (3H, s), of 3.73 (3H, s), is 6.78 (1H, DD), 6,88-to 7.00 (4H, m), 7,05 and 7.36 (7H, m), 7,42 (1H, d), of 7.48 (1H, s) M. D.

P R I m e R 12. This example illustrates how to obtain (E)-methyl 2-[2-(3-pyrimidine-2-yl-oxigenation)phenyl]-3-methoxypropionate (compound No. 22 of table.4).

A mixture of sodium salt of 3-methoxythiophene obtained by processing of 2.8 g of 3-methoxythiophene 0.8 g of sodium hydroxide in 20 ml of methanol, followed by evaporating the solution to dryness, 4.3 g of 2-bromoferrocene acid and 0.4 g of copper chloride (I) in 25 ml of dry DMF was heated overnight under reflux. The reaction mixture was then cooled, poured into water and acidified with diluted hydrochloric acid. The aqueous mixture was extracted three times with ether and the combined ether extracts in turn was twice subjected to extraction with dilute hydroxide solution was naterual ether.

The combined ether extracts are washed three times with water, dried and evaporated, resulting in the 3.5 g (content of 96.8 per cent, determined by gas chromatography) oily liquid orange. The obtained oily liquid was kept overnight at room temperature with acidic methanol. After the usual processing was obtained 2.9 g (content of 91% , determined by gas chromatography) methyl-2-(3-methoxyphenyl)phenylacetate in the form of a yellow liquid, which without further purification was used in the next stage.

1H NMR, : of 3.64 (3H, s), 3,74 (3H, s), 3,86 (2N, C) M. D.

IRmax. (film): 1739 cm-1.

0,86 g of methyl 2-(3-methoxyphenyl)phenylacetate and of 2.08 g (excess) of pyridinecarboxamide was heated at 200aboutC in nitrogen atmosphere. After 3 h the reaction mixture was cooled and distributed between dilute hydrochloric acid and ethyl acetate. The acidic aqueous layer was twice subjected to extraction with ethyl acetate and the combined organic phases were extracted three times with dilute sodium hydroxide solution. United alkaline phase was acidified with concentrated hydrochloric acid and three times was subjected to extraction with ethyl acetate. These on razno-white solid. Obtained off-white solid was treated with a methanol solution of hydrogen chloride and after standard treatment received of 0.44 g of methyl 2-(3-oxigenation)phenylacetate as a red oily liquid (purity determined by gas chromatography, 90,5%), which without further purification was used in the next stage.

IRmax.: 3384, 1738 cm-1.

A solution of 0.44 g of crude metal-2-(3-oxigenation)phenylacetate and 1.92 ml of methylformate in 2 ml of dry DMF was added dropwise to a stirred suspension of 0.21 g (55% dispersion in oil, pre-washed with petroleum ether) of sodium hydride in 3 ml of dry DMF) at 0-5aboutC. After 15 min the mixture was allowed to warm to room temperature. After 2.5 h the reaction mixture was poured into water, acidified with concentrated hydrochloric acid and three times was subjected to extraction with ether. The combined ether extracts are washed three times with water, dried and evaporated, resulting in the 0,49 g resin red. Received the red resin was dissolved in 5 ml of DMF and cooled the solution to 0aboutBack To the prepared solution was added 0,132 g of potassium carbonate, and then dropwise a solution of 0,111 g dimethylsulfate in DMF. After p is yennie ether extracts are washed three times with water, was dried and evaporated, to deliver 0.45 g of methyl 2-[2-(3-oxigenation)phenyl]-3-methoxypropionate resin red.

IRmax3240, 1709, 1665 cm-1M+316.

1H NMR, : the 3.65 (3H, s), 3,76 (3H, s), 7,47 (1H, s) M. D.

0.4 g of crude (E)-methyl 2-[2-(3-oxigenation)phenyl]-3-methoxypropionate was treated with 0.45 g of 2-chloropyrimidine and 0.17 g of potassium carbonate in 10 ml of dry DMF at 80-90aboutC in nitrogen atmosphere. The results showed gazebocreations.com analysis, after 4.5 h the reaction mixture, there was one product of the reaction, the reaction mixture was cooled, poured into water and four were subjected to extraction with ether. The combined ether extracts of yellow color was twice washed with water, dried and evaporated, to deliver 0.39 g of resin orange. After chromatography using as eluent ether was obtained 0.34 g of target compound in the form of a viscous resin orange.

IRmax1706, 1632 cm-1.

1H NMR, : of 3.64 (3H, in), 3.75 (3H, s), 6,97-7,06 (3H, m), 7,08 for 7.12 (1H, d), 7,25-to 7.35 (4H, m), 7,46-of 7.48 (1H, d), 7,49 (1H, s), 8,53-8,56 (2H, d) M. D.

P R I m e p 13. This example illustrates how to obtain (E)-methyl 2-/2-(3-phenylthiophene)phenyl]-3-methoxypropane and the Nile)-3-methoxypropionate, derived from o-bromophenylacetate, methylformate and sodium hydride followed by addition of potassium carbonate and dimethylsulfate in two stages according to the method described in example 7 for a similar transformation, 0,69 g (0,005 mol) of anhydrous potassium carbonate and a catalytic amount of copper chloride were mixed and heated with stirring to 175aboutC. After 10 h, the reaction mixture was cooled to ambient temperature and was dissolved in 50 ml of DMF. The resulting solution was poured into 100 ml of water and the resulting emulsion was twice subjected to extraction with ether (100 ml). The combined ether extracts were washed successively with water (twice, 100 ml), twice with 2 m sodium hydroxide solution (100 ml) and twice with water (100 ml). Obtained after washing the ether solution was dried, filtered and evaporated to dryness under reduced pressure. After chromatography using as an eluent of chloroform received 0,83 g of target compound in the form of a viscous oily liquid.

1H NMR (60 MHz): to 3.52 (3H, s) to 3.64 (3H, s), 6,5-7,3 (13H, m), 7,42 (1H, s) M. D.

P R I m e R 14. This example illustrates how to obtain (E)-methyl 2-[2-(3-phenylthiophene)phenyl]-3-methoxypropanol-S,S - dioxide (soedarsono, obtained as described in example 13 by the method, and 1.1 g (0,0079 mol) of anhydrous potassium carbonate was mixed with a catalytic amount of copper chloride and copper bronze. The mixture was heated for 10 h at 170aboutC in nitrogen atmosphere. After that, the melt was cooled to ambient temperature and the residue was dissolved in 50 ml of DMF. The resulting solution was diluted with 100 ml of ether and filtered to remove inorganic salts. The solution is then washed with 100 ml water, twice with 2 m sodium hydroxide solution (100 ml), again with 100 ml water and 100 ml of saturated solution of sodium chloride. The ether solution was dried, filtered and evaporated to dryness under reduced pressure. After chromatography of the residue using as eluent hexane and chloroform received 0.66 g of the target compound.

1H NMR (60 MHz): of 3.46 (3H, s), of 3.57 (3H, s), 6,6-8,0 (14N, m) M. D.

P R I m e R 15. This example illustrates how to obtain (E)-methyl 2-/2-(3-belinfante)phenyl/-3-methoxypropionate (compound No. 4 of table.1).

1,365 g (0,0074 mol) 3-oxydiphenylene, 1 g (0,0037 mol) of 2-(2-bromophenyl)-3-methoxypropionate, obtained as described in example 13 by the method, and 0,517 g (0,0037 mol) of anhydrous potassium carbonate was mixed with a catalytic calico in 20 ml of DMF. The resulting solution was distributed between ether and water. The ether layer was washed with water (twice 100 ml) and twice 1M sodium hydroxide solution (100 ml), then dried, filtered and evaporated to dryness under reduced pressure. The remainder of the resin was purified by chromatography, using as eluents hexane and dichloromethane. The result obtained 0.40 g of the target compound.

1H NMR (60 MHz): only 3.57 (3H, s) to 3.67 (3H, s), of 5.75 (1H, broad), of 6.3 to 7.4 (13H, m), 7,44 (1H, s) M. D.

P R I m e R 16. This example illustrates how to obtain (E)-methyl 2-[2-(3-N-methylenedioxy)phenyl] -3-methoxypropan - noate (compound No. 5 of table.1).

300 mg (0.01 mol) of 80% dispersion of sodium hydride in oil was twice washed with hexane (50 ml) to remove the oil and then suspended in 10 ml of dry DMF. To the resulting suspension was added a solution (290 mg) (E)-methyl 2-[2-(3-belinfante)phenyl] -3-methoxypropane - one, obtained as described in example 15 by the way, in 10 ml of DMF at this rate, to ensure an even allocation of gas bubbles. After cessation of gas evolution, the mixture was stirred for another 15 min and added to it for 5 min 2 ml (larger surplus) iodomethane. Mixing what was Dorgali extraction with ether (50 ml), was dried, filtered and evaporated to dryness under reduced pressure, to deliver 211 mg of the target compound as a viscous oily liquid.

1H NMR (60 MHz): 3,20 (3H, s), of 3.54 (3H, s), the 3.65 (3H, s), 6,3-7,4 (12, m), 7,44 (1H, s) M. D.

P R I m e R 17. This example illustrates how to obtain (E)-methyl 3-methoxy-2-{ 2-[3- (-oxybenzyl)phenoxy]phenyl}-propene-one (compound N 380 table.1).

Finely crushed 31.0 g of 3-oxybenzyl alcohol and mixed it with 34.6 g of potassium carbonate, and 26.9 g of 2-bromoferrocene acid and chloride of copper (large spatula) in nitrogen atmosphere. The mixture was heated to 140aboutWith and intensively stirred at this temperature for 3.5 hours and Then to stir the melt was added 60 ml of DMF, the solution was cooled, poured into water and acidified with diluted hydrochloric acid. The aqueous layer was subjected to extraction with ether, the ether extracts washed with water, dried and evaporated, resulting in the 42,03 g of 2-(3-oxymethylene)phenylacetic acid as a brown oily liquid, which without further purification was used in the next stage.

41,0 g of the resulting crude acid was heated for 3.5 h under reflux in 600 ml of methanol with the addition of 2.5 ml of the Lenna aqueous solution of sodium hydroxide, and then water, dried and evaporated, resulting in the 26,31 g of brown oily liquid. 1,31 g was purified using high performance liquid chromatography, using as eluent a mixture of ethyl acetate and hexane, taken in the ratio 1: 1. The result was obtained pure 2-(3-oxymethylene)phenyl acetate as a pale yellow oily liquid.

1H NMR (400 MHz): 2,12 (1H, s), of 3.60 (3H, s), of 3.69 (3H, s), to 4.62 (2H, s), to 6.95 (1H, s), 6,85-6,90 (2H, t),? 7.04 baby mortality-7,14 (2H, m), 7,21-to 7.32 (3H, m) M. D.

IR (film): 3450, 1742 cm-1.

A mixture of 25.0 g of crude methyl 2-/3-oxymethylene/phenylacetate and 56 ml of methylformate in 50 ml of dry DMF was added dropwise within 30 minutes with 5aboutTo sodium hydride (7,35 g 60% dispersion in oil, washed with hexane). After stirring for a further 30 minutes at 5aboutTo the mixture was allowed to warm to room temperature over several hours and then left to stand overnight. After the reaction mixture was poured into water and subjected to extraction with ether. The aqueous layer was acidified with diluted hydrochloric acid and subjected to extraction with ether. The ether extracts were dried and evaporated, resulting in the 32,19 g of crude methyl 2-[2-(3-oxymethylene)]-phenylpropanoate in VG potassium carbonate was added to the mixture dropwise a solution of 11.6 g of dimethylsulfate in 20 ml of DMF for 10 minutes The mixture was allowed to warm to room temperature over several hours and left to stand overnight. Then it was poured into water, acidified with diluted hydrochloric acid and subjected to extraction with ether. The ether extracts were washed with water, dried and evaporated, resulting in the 14,38 g of orange-brown oily liquid. After purification using high performance liquid chromatography was obtained 7.8 g (E)-methyl 3-methoxy-2-[2-(3-oxymethylene)phenyl] propanoate in the form of a pinkish crystalline substance.

1H NMR (270 MHz): 2,55 (1H, s) to 3.58 (3H, s), 3,74 (3H, s) 4,55 (2H, s), 6,8-7,28 (8H, m), 7,44 (1H, s) M. D.

IRmax., (nujol): 3515, 1705, 1625 cm-1.

Part of the obtained alcohol (0,314 g) was stirred in 5 ml of dry methylene chloride, were added 0,564 g of pyridinium dichromate and the mixture was stirred for 4 h at room temperature. Then it was filtered and the precipitate was washed with ether. Methylene chloride and ether after washing were combined and evaporated, resulting in the 0,309 g (E)-methyl 3-methoxy-2-[2-(3-formylphenoxy) phenyl]propanoate in the form of a brown oily liquid.

1H NMR (270 MHz): 3,59 (3H, s), the 3.65 (3H, s), 6,98 (1H, d), 7,17 and 7.36 (4H, m), 7,40-7,47 (3H, m), 7,47 (1H, s), 7,55 (1H, d) M. D.

1H NMR (400 MHz): 2,30 (1H, d), of 3.57 (3H, s), and 3.72 (3H, s), 5,78 (1H, d), PC 6.82 (1H, d), 6,91 (1H, d), 7,02-was 7.08 (2H, m), 7,10-7,16 (1H, m), 7,20-7,38 (8H, m), 7,45 (1H, s) M. D.

IRmax. (film): 3460, 1715, 1635 cm-1.

P R I m e R 18. This example illustrates how to obtain (E)-methyl 3-methoxy-2-{2-[3-(2-pyridyloxy)phenoxy]phenyl} of propenoate (compound No. 6 of table.2).

0.28 g of carbonate behold the aqueous described in example 8 way, and to 0.19 g of 2-pyridone in hexane. The mixture is boiled for 3 hours under reflux in the dark for what was wrapped in the reaction flask in aluminum foil, and then left to stand overnight. Then hexane drove away, and the residue was dissolved in an aqueous solution of sodium bicarbonate and then with water, dried and evaporated, to deliver 0,72 g orange resin. The resulting resin was purified using high performance liquid chromatography, using as eluent a mixture of ether and hexane, taken in the ratio 1:1. The result has been 0,188 g of target compound in the form of a colourless resin.

1H NMR (270 MHz): of 3.60 (3H, s), 3,76 (3H, s), 5,32 (2H, s), is 6.78 (1H, d), 6,84-of 6.96 (3H, m),? 7.04 baby mortality-7,16 (1H, m), 7,21-7,31 (3H, m), of 7.48 (1H, s), 7,52-of 7.60 (1H, m), 8,15 (1H, d), M. D.

IRmax. (film): 1715, 1670, 1645, 1600 cm-1.

P R I m e R 19. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-pyrimidine-2-yl-oxymethylene) phenyl] propenoate (compound N 85 from table.2).

0.5 g of (E)-methyl 3-methoxy-[2-(3-oxymethylene)phenyl]propanoate, obtained as described in example 17 by the way, a few ml of DMF was added to sodium hydride (0,072 g 60% dispersion in oil, washed with hexane) and stirred in 10 ml of dry DMF at room templei to stand overnight. Then it was poured into water, acidified and subjected to extraction with ether. The ether extracts were dried and evaporated, to deliver 0.95 g of a yellow oily liquid. After cleaning it using high-performance liquid chromatography, using as eluent a mixture of ethyl acetate and hexane, taken in the ratio 1:1, was obtained in 0.104 g of pure target compound in the form of an oily liquid.

1H NMR (270 MHz): of 3.60 (3H, in), 3.75 (3H, s), of 5.39 (2H, s), 6,86-of 6.96 (3H, m), 7.03 is-7,31 (6N, m), 7,49 (1H, s), and 8.50 (2H, d) M. D.

IRmax(film): 1713, 1640 cm-1.

P R I m e R 20. This example illustrates how to obtain (e,E)- and (E, Z)-methyl 3-methoxy-2-{2[3-(4-nitrostyryl)phenoxy] phenoxy}phenyl - propanoate (a mixture of compounds N 403 table.1).

1.39 g of dimethylphosphite in 5 ml of dry DMF was added dropwise to a stirred suspension of sodium hydride (0,61 g of a 50% dispersion in oil, washed with hexane) in 10 ml dry DMF at 20aboutC. after adding and mixing the mixture for a further 20 min, it was added dropwise 7.0 g (purity 70%) of (E)-methyl 3-methoxy-2-[2-(3-bromomethylphenyl)phenyl] propanoate, obtained as described in example 8 by the way. The reaction mixture was left to stand for 60 hours, after hours is sutured and evaporated, receiving the viscous yellow resin, which was purified using flash chromatography, using as eluent 5% methanol in ethyl acetate. The result has been a 1.50 g of the phosphonate (E)-methyl 3-methoxy-2-(3-/diethylphosphonate - Teal/phenoxy)- phenylpropanoate in the form of almost colorless oily liquid.

1H NMR (400 MHz): 3,13 (2H, d), 3,62 (3H, s), 3,66 (3H, s), 3,68 (3H, s), of 3.78 (3H, s), 6,85 (1H, d), 6,92 (2H, d), of 7.00 (1H, d), 7,13 (1H, t), 7,20-7,31 (4H, m), of 7.48 (1H, s) M. D.

IRmax(film): 1715, 1645 cm-1.

0,61 g of the resulting phosphonate in 5 ml of dry DMF was added dropwise to sodium hydride (0,072 g of a 50% dispersion in oil, washed with hexane), mixed in 10 ml of dry DMF in 5aboutC in nitrogen atmosphere. After the addition was finished the reaction mixture was heated to room temperature and was stirred for 15 minutes then to it was added slowly dropwise 0,227 g N-nitrobenzaldehyde in 5 ml dry DMF and stirred overnight at room temperature, then adding water and subjected to extraction with ether. The ether layer was dried and evaporated, resulting in the viscous yellow liquid which was purified using high performance liquid chromatography, using as eluent toy resin, representing a mixture (in the ratio 5:1) /Z/ - /E/-stilinovich isomers.

1H NMR (270 MHz): (/Z/-isomer) of 3.57 (3H, s), 3,74 (3H, s), to 6.58 (1H, d), 6,72 (1H, d), 6,72-6,98 (3H, m), 7,05 and 7.36 (7H, m), 7,45 (1H, s), of 8.06 (2H, d) M. D.

By boiling the mixture under reflux in toluene with traces of iodine were obtained mixture with a ratio of (E)- and (Z)-isomers of 85:15.

1H NMR (400 MHz), ((E)-isomer): 3,62 (3H, s), of 3.78 (3H, s), 6,92-to 7.35 (10H, m), 7,49 (1H, s), to 7.61 (2H, d), by 8.22 (2H, d) M. D.

P R I m e R 21. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-benzoyloxymethyl)phenyl] propenoate (compound 398 table.1).

0.5 g (purity 75%) of (E)-methyl 3-methoxy-2-(3-bromomethylphenyl)phenylpro - Pinout, obtained as described in example 8 by way of 0.13 g of benzoic acid and 0,076 g of potassium carbonate was stirred over night at room temperature in dry DMF. Then to the mixture was added to water and subjected to the extraction of the diluted aqueous solution of bicarbonate, dried and evaporated, resulting in the 0,49 g of yellow viscous oily liquid, which was purified using high performance liquid chromatography, using as eluent a mixture of hexane and ethyl acetate, taken from the, is), 5,31 (2H, s), 6,93 (1H, d), of 6.96 (1H, d), 7,06 (1H, s), 7,12 (1H, d), 7,16 (1H, d), 7,44 (2H, t), 7,25-to 7.32 (2H, m), 7,47 (1H, s), 7,55 (1H, d), with 8.05 (2H, d).

P R I m e R 22. This example illustrates obtaining bromide salt (E)-methyl 3-methoxy-2-{ 2-[3-(triphenylphosphonio - dimetil)phenoxy] phenyl}-propanoate (compound N 404 of the table.1).

Was stirred for 4 hours at room temperature 4,58 g (purity 70%) of (E)-methyl 3-methoxy-2[2-(3-bromomethylphenyl)phenyl] propanoate, obtained as described in example 8 by the method, and of 2.33 g of triphenylphosphine in 40 ml of dry DMF and the resulting mixture was left to stand overnight. After that, the solvent drove and got a thick residue, which is triturated in a mixture of ether and ethyl acetate, receiving the result of 4.38 g of the target compound as a yellow-white crystalline substance; so pl. 176-177aboutC.

1H NMR (270 MHz): of 3.56 (3H, s), 3,74 (3H, s), 5,28 (2H, d), 6.48 in (1H, s), 6,62 (1H, d), 6,77 (1H, d), 6,97 (1H, d),? 7.04 baby mortality (1H, t), 7,10-7,28 (3H, m), 7,40 (1H, s), 7,54-7,80 (15 NM, m) M. D.

P R I m e R 23. This example illustrates how to obtain (e,E)-methyl 3-methoxy-2-[2-(3-sterigenics)phenyl]propenoate (compound No. 18 of table.1).

1.0 g of bromide salt (E)-methyl 3-methoxy-2-[2-(3-triphenylphosphonium)phenoxy] phenylpropanoate obtained are described in primeexam) in 5 ml dry DMF. The result has been an orange solution. After the evolution of hydrogen (2 h) were added 0.66 g of benzaldehyde in 5 ml of dry DMF and the reaction mixture was stirred at room temperature for 20 h, and then was heated for 2 h at 60aboutC. thereafter, thereto was added water and subjected to extraction with ethyl acetate. The organic layer was dried and evaporated, resulting in the 1.3 g of yellow oily liquid, which was purified using high performance liquid chromatography, using as eluent a mixture of THF and hexane, taken in the ratio 1:4. The result has been 0,362 g of a mixture of target compound and the corresponding (Z)-stilnovo isomer in a ratio of 1:1.

By boiling this mixture and under reflux for several hours in toluene with the addition of a crystal of iodine was obtained (E)-isomer as a colourless resin.

1H NMR (270 MHz): to 3.64 (3H, s), of 3.77 (3H, s), to 6.88 (1H, d), of 6.96-7,40 (10H, m), 7,49 (1H, s) of 7.48 (2H, m), M. D.

IRmax. (film): 1710, 1640 cm-1.

P R I m e R 24. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-phenoxycarbonylamino)phenyl] propenoate (compound No. 50 of table.1).

To 2,43 g (E)-methyl 3-methoxy-2-[2-(3SUP>aboutWith added chromic acid obtained by dissolving 6.5 g of chromium trioxide 18.5 ml of water with the addition of 5.5 ml of concentrated sulfuric acid, to obtain a stable reddish and entry (according to gas chromatography) of the total number of initial alcohol in the reaction. After that, the mixture was poured into water and subjected to extraction with ether. The ether extracts were washed with water, dried and evaporated, to deliver 2,495 g (E)-methyl 3-methoxy-2-[2-(3-carboxyphenoxy) -phenylpropanoate] in the form of a pale yellow oily liquid.

1H NMR (270 MHz): of 3.60 (3H, s), 3,76 (3H, s), to 6.95 (1H, d), 7,14-7,40 (5H, m) to 7.50 (1H, s), 7,66 (1H, s), 7,78 (1H, d), a 9.35 (1H, broad s) M. D.

IRmax. (film): 3500-2500, 1725, 1640 cm-1.

0.33 g of carboxylic acid, obtained in the previous phase, was stirred in 10 ml of dry DMF and treated of 0.11 ml of oxalicacid and one drop of dry DMF. The reaction mixture was stirred for 45 min, left to stand overnight and evaporated, resulting in the crude (E)-methyl 3-methoxy-2-[2-(3-chlorocarbonates) phenyl] propanoate in the form of orange-yellow oily liquid.

IRmax(film): 1760, 1715, 1640 cm-1.

To the acid chloride of the acid obtained in PRS was stirred at room temperature for 1.5 h, was poured into water and subjected to extraction with ether. The ether extracts were washed with dilute sodium hydroxide solution and then with water, dried and evaporated, resulting in the 136 mg of the target compound as an orange oily liquid.

1H NMR (270 MHz): of 3.60 (3H, s), of 3.77 (3H, s) 6,94 (1H, d), 7,14 (2H, t), 7.23 percent-7,38 (3H, m), 7,47 (1H, s), to 7.61 (1H, t), 7,72 (1H, d) M. D.

IRmax. (film): 1755, 1710, 1640 cm-1.

P R I m e R 25. This example illustrates how to obtain (E)-methyl-2-{ 2-[3-(6-chloropyrimidine-4-yloxy)phenoxy] phenyl} -3 - methoxypropionate (compound No. 89 of table.2).

To a stirred solution of 1.0 g of (E)-methyl 2-[2-(3-oxygenase)phenyl] -3-label-dipropionate, obtained as described in example 1, in 10 ml) was added sequentially and 0.46 g of potassium carbonate, or 0.027 g of the chloride of copper and 0.41 g of 4,6-dichloropyrimidine and the resulting mixture was stirred for 10 h at room temperature. Then it was diluted with water and subjected to extraction with ether. The extracts were washed successively with an aqueous solution of sodium bicarbonate and water, dried, concentrated and chromatographically, using as eluent a mixture of ether and hexane, taken in the ratio 1: 1. The result has been 0.39 g (yield 28%) of slevogt), for 6.81 (1H, DD), of 6.90 (2H, m), 7,03 (1H, m), 7,17 (1H, t), 7,26-6,36 (3H, m), 7,49 (1H, s), 8,59 (1H, s) M. D.

P R I m e R 26. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-pyrimidine-4-idoxifene)phenyl] propenoate (compound N 92 of the table.2).

A solution of 0.27 g of hypophosphite of sodium in 5 ml of water was added dropwise with stirring to a mixture of 0.4 g of (E)-methyl-2-{2-[3-(6-chloropyrimidine-4-yloxy)phenoxy] phenyl}-3 - methoxypropionate, obtained as described in example 25 method, 0.2 g of potassium carbonate and 0.08 g of 5% palladium on coal in 4 ml of THF. The resulting mixture was stirred for 2 h at room temperature, filtered through "Hyflo and washed with ethyl acetate and water. The combined filtrate and washing liquid were separated into aqueous and organic layers. The latter was dried, concentrated and chromatographically, using as eluent a mixture of ether and hexane, taken in the ratio 1:1. The result has been to 0.19 g (yield 52%) of target compound in the form of a colorless oily liquid.

1H NMR (270 MHz): 3,61 (3H, in), 3.75 (3H, s), of 7.75 (1H, t), of 7.48 (1H, s), 8,56 (1H, d), 8,76 (1H, s) M. D.

P R I m e R 27. This example illustrates how to obtain (E)-methyl 3-methoxy-2-{ 2-[3-(3-nitrophenoxy)phenoxy]phenyl} -propanoate (compound No. 132 table.1)sunnym in example 13 by the way 1.0 g of potassium carbonate and 1.0 g of copper chloride was stirred for 5 hours at 170-180aboutC, then cooled, diluted with water and subjected to extraction with ether. The extracts were washed successively with an aqueous solution of sodium hydroxide and brine, dried and concentrated, obtaining the result of 3.12 g of a brown oily liquid. By chromatography was carried out using as eluent mixtures with various proportions of ether (20%) and hexane were obtained 1.06 g (yield 34%) of target compound as a yellow oily liquid.

1H NMR (270 MHz): of 3.60 (3H, s), 3,76 (3H, s), 6,66-6,83 (3H, m), 7,02 (1H, d), 7,18 (1H, d), 7,22-7,38 (3H, m), 7,45-7,52 (1H, m), of 6.49 (1H, s), 7,78 (1H, m), 7,92-of 7.97 (1H, m) M. D.

P R I m e R 28. This example illustrates how to obtain (E)-methyl 3-methoxy-2-{ 2-[3-(3-methoxyphenoxy)phenoxy] - phenyl} - propanoate (compound N 372 table.1).

0.50 g (E)-methyl 3-methoxy-2-(2-[3-methylphenoxy]phenyl)propanoate, obtained as described in example 8 by the way, 0.32 g of 1,3-dibromo-5,5-dimethylhydantoin and 0,033 g isobutyronitrile boiled under reflux in 40 ml of carbon tetrachloride, irradiating a tungsten lamp (power: 400 watts. After one hour the mixture was cooled and poured into water. The organic layer was separated, washed with water, veil-2-methoxy-2-[2-(3-bromomethylphenyl)phenyl] - propenoate, which was used further without additional purification (see example 8, data1H NMR).

A solution of 0.41 g of the crude bromide in 4 ml of dry DMF was added to a solution of 3-methoxyphenoxy sodium (obtained from 3-methoxyphenol and sodium hydride) in 6 ml dry DMF and the mixture was stirred for 4 h, then left to stand overnight. The reaction mixture was then poured into a dilute aqueous solution of hydrochloric acid and subjected to extraction with ethyl acetate. The organic fraction was dried and evaporated, resulting in the brown oily liquid, which was purified using high performance liquid chromatography, using as eluent a mixture of petroleum ether 40/60 and ethyl acetate, taken in the ratio of 7:3. The result was obtained 0.20 g of target compound in the form of a colourless resin.

IRmax(film): 1715, 1640 cm-1.

1H NMR (400 MHz): of 3.60 (3H, s), of 3.73 (3H, s), of 3.77 (3H, s), 4,99 (3H, s), 6,50-6,55 (3H, m), 6,88-to 6.95 (2H, m), 7,05 (1H, s), 7,09-7,20 (3H, m), 7.24 to 7,31 (3H, m), 7,47 (1H, s) M. D.

P R I m e R 29. This example illustrates how to obtain (E)-methyl 3-methoxy-2-[2-(3-benzoylperoxy)phenyl]-propanoate (compound No. 12 of table.1).

10.0 g of methyl 2-(3-oxymethylene)phenylacetate, the si in one 15,85 g Harrogate pyridinium. After stirring the mixture at room temperature for 2.5 h, it was filtered and the filtrate was evaporated, resulting in the 8,48 g of methyl 2-(3-formylphenoxy)phenylacetate as an orange oily liquid, which was sufficiently pure to be used without additional purification.

IRmax(film): 1740, 1700 cm-1.

1H NMR (270 MHz): 3,59 (3H, s), of 3.69 (2H, s), 6,92 (1H, d), 7,14-7,20 (1H, t), 7.23 percent-7,37 (3H, m), the 7.43 (1H, m) to 7.50 (1H, t), 7,60 (1H, DD), for 9.95 (1H, s) M. D.

To 2.30 g of the cooled mixed solution obtained at the previous stage of the aldehyde in THF was added dropwise phenylmagnesium (2,84 ml of 3M solution in ether) with such speed that the temperature did not rise above 30aboutC. After adding (35 min) the reaction mixture was slowly heated to room temperature, stirred overnight and then was cooled in an ice bath, carefully adding water. After that it was added diluted hydrochloric acid and subjected to extraction with ethyl acetate. The extracts were dried and evaporated, resulting in the yellow oily liquid, which was purified using flash chromatography, using as eluent a mixture of hexane and ethyl acetate, taken in Soi liquid.

1H NMR (270 MHz): only 3.57 (3H, s), 8,68 (2H, s), 5,79 (1H, s), 6,79-of 6.90 (2H, m), 7,05-7,13 (3H, m), 7.18 in-7,40 (N, m) M. D.

0,91 g oxyethira obtained in the previous phase was stirred at room temperature in 25 ml of methylene chloride with the addition of two spatulas of celite. Then to the mixture was added 0.65 g Harrogate pyridinium and stirred for 3 h, then was filtered, the filtrate was evaporated and purified using high-performance liquid chromatography, using as eluent a mixture of hexane and ethyl acetate, taken in the ratio of 3:1. The result was obtained 0.56 g of methyl 2-(3-benzoylperoxy)phenyl acetate as a pale yellow resin.

1H NMR (270 MHz): of 3.60 (3H, s), 3,70 (2H, s), 6,93 (1H, d), 7,10-7,63 (10H, m), 7,81 (2H, d) M. D.

IRmax(film): 1740, 1660 cm-1.

The resulting product was transferred into the target compound by treatment with sodium hydride and methylformate followed by the addition of potassium carbonate and dimethylsulfate, processing washed in two stages, as described in example 7 for a similar transformation.

IRmax(film): 1710, 1660, 1635 cm-1.

1H NMR (270 MHz): of 3.60 (3H, in), 3.75 (3H, s), 6,98 (1H, d), 7,12-7,20 (2H, m), 7,26-7,52 (8H, m), 7,47 (1H, s), 7,55-7,63 (1H, m), 7,80 (2H, DD) M. D.

the (compound No. 9 of table.1).

To 1.68 g of methyl 2-{[3-( -hydroxy)benzyl]phenoxy}phenylacetate obtained as described in example 29 by the way, was added dropwise in 5aboutC and stirred for 3.28 g triperoxonane acid. After adding to the mixture was added dropwise slowly 2.24 g of triethylsilane. The resulting clear solution was stirred over night, diluted aqueous sodium bicarbonate solution, dried, concentrated and purified using high-performance liquid chromatography, using as eluent a mixture of hexane and ether, taken in the ratio of 4:1. The result has been of 1.03 g of methyl 2-(3-benzoylperoxy)phenylacetate in the form of a colorless oily liquid.

IRmax. (film): 1742 cm-1.

The resulting product was transferred into the target compound by treatment with sodium hydride and methylformate and the subsequent addition of potassium carbonate and dimethylsulfate. Processing of data was performed in two stages, as described for similar transformations in example 7.

IRmax. (film): 1708, 1635 cm-1.

1H NMR (270 MHz): of 3.56 (3H, s), and 3.72 (3H, s), 3,93 (2H, s), 6,76-6,93 (4H, m), 7,08-7,31 (10H, m), 7,47 (1H, s) M. D.

P R I m e R 31. This example illustrates how to obtain (E)-methyl-3-bromoferrocene acid, 29,2 g of 3-NITROPHENOL, of 27.6 g of potassium carbonate and 0.5 g of copper chloride was heated for 6 h under stirring at 130aboutC.

After cooling the mixture was poured into 500 ml of water, acidified with concentrated hydrochloric acid and three times carried out the extraction with ethyl acetate (portions of 200 ml). The extracts were dried, filtered and concentrated, obtaining a dark oily liquid, which was dissolved in 400 ml of methanol with the addition of 4 ml of concentrated sulfuric acid and the resulting solution was boiled for 3 h then the reaction mixture was concentrated and the residue was dissolved in 300 ml of ethyl acetate. The resulting solution was sequentially washed with 1M aqueous solution of sodium hydroxide (twice, 100 ml) and brine, dried, filtered and concentrated, obtaining a dark oily liquid. After distillation (oven temperature 220aboutWith the pressure of 0,2 mm RT. Art.) received 16,74 g (yield 58% based on 2-bromoferrocene acid) methyl-2-(3-nitrophenoxy)-phenylacetic acid in the form of a transparent pale oily liquid.

1H NMR (270 MHz): of 3.60 (3H, s), 3,70 (2N, C) and 6.9 to 8.0 (8H, m) M. D.

IRmax(film): 1739 cm-1.

A mixture of 15 g of methyl 2-(3-nitrophenoxy)phenylacetate, 100 ml atory boil. After 30 min the mixture was cooled and filtered, the excess of iron powder. The filtrate was poured into 700 ml of water and twice subjected to extraction with ether. The ether extracts are neutralized by mixing with an aqueous sodium bicarbonate solution, then dried, filtered and concentrated, obtaining the result of 13.0 g (yield 97%) of 2-(3-aminophenoxy)phenylacetate in the form of a pale yellow oily liquid.

1H NMR (270 MHz): 3,63 (3H, s), 3,68 (2H, s), 3,9 (1H, broad s), a 6.2 to 7.3 (8H, m) M. D.

IRmax(film): 3400, 3373, 1733 cm-1.

The mixture 11,54 g of methyl 2-(3-aminophenoxy)phenylacetate and 27.7 ml methylformate in 25 ml DMF was added dropwise with stirring to a cooled with ice to a temperature below 10aboutWith the suspension of 3.25 g of sodium hydride in 50 ml of DMF (liberation of gas bubbles). After the addition was finished the reaction mixture was stirred at room temperature for 3 h, poured into water, acidified with concentrated hydrochloric acid and subjected to extraction with ethyl acetate. The extracts were washed with brine, dried and concentrated, obtaining a viscous yellow oily liquid. To a mixed solution of the liquid 50 ml of DMF was added sequentially 12.4 g of potassium carbonate in water and subjected to extraction with ethyl acetate. The extracts were washed with water, dried and concentrated, resulting in the 13,67 g (yield 93%) of (E)-methyl 2-[2-(3-formamidine)phenyl]-3-methoxypropionate in the form of a transparent resin green.

1H NMR (270 MHz): of 3.60 (3H, s), of 3.78 (3H, s), 7,47 (1H, s) M. D.

IRmax(film): 3309, 1702, 1606 cm-1.

To a stirred solution of (E)-methyl 2-[2-(3-formamidine)phenyl]-3 - methoxypropionate (13,67 g) in 100 ml of methanol was added dropwise with 7.8 ml of phosphorylchloride, maintaining the temperature in the process of adding using a cooling bath below the 50aboutC. After stirring for 20 min the reaction mixture was poured into 500 ml of water, neutralize with sodium bicarbonate and subjected to extraction with ether. The extracts were dried and concentrated, obtaining a yellow oily liquid which was subjected to chromatography using as eluent ether. The result has been to 8.57 g (yield 68%) of (E)-methyl 2-[2-(3-aminophenoxy)phenyl]-3-methoxypropionate in a solid yellow color. So pl. 83-85aboutC.

1H NMR (270 MHz): 3,6 (2H, broad s), 3,62 (3H, s), of 3.77 (3H, s), 6,2-6,4 (3H, m), the 6.9 and 7.3 (5H, m), of 7.48 (1H, s), M. D.

IRmax. (film): 3450, 3370, 1703, 1632 cm-1.

A solution of (E)-IU is SUP>With 1 ml of 5.8 M hydrochloric acid. After that mix the solution was treated at 10aboutWith a solution of 0.1 G. of sodium nitrite in 2 ml of water. After 20 min the resulting solution (containing salt, page) was added to a stirred mixture of 0.5 ml of glacial acetic acid saturated with sulfur dioxide, with the addition of 0.1 g of copper chloride (liberation of gas bubbles). After 30 min the reaction mixture was poured into water and subjected to extraction with ether. The ether extracts neutralize saturated aqueous sodium bicarbonate, dried, concentrated, resulting in the 0.14 g (E)-methyl 2-[2-(3-chlorosulfonylphenyl) phenyl] -3-methoxypropionate in the form of a yellow oily liquid.

IRmax. (film): 1710, 1636 cm-1.

To a solution of 0.14 g of methyl 2-[2-(3-chlorosulfonylphenyl)phenyl]-3-methoxypropane-ATA in 0.5 ml of pyridine was added dropwise at room temperature and mixing 0.05 ml of aniline.

After 3 h the reaction mixture was poured into water, was added a 2M hydrochloric acid to slightly acid reaction and subjected to extraction with ether. The ether extracts were washed with brine, dried, concentrated and subjected to chromatography, using as eluent ether. The result has been 0,145 g of the target issue for lighting-1.

1H NMR (270 MHz): 3,55 (3H, s), of 3.69 (3H, s), 6,53 (1H, broad s), 6,8 (1H, m), 7,0-7,4 (N, m), the 7.43 (1H, s) M. D.

P R I m e R 32. This example illustrated obtaining (E)-methyl-2-{ 2-[3-(3-bromobenzylamine)phenoxy] phenyl}-3-methoxypropionate (compound 421 N of the table.1).

To a stirred solution of 0.5 g of (E)-methyl 2-[2-(3-aminophenoxy)phenyl] -3-methods - of copropagate, obtained as described in example 31 by the way, in 20 ml of dichloromethane with the addition of 0.17 g of triethylamine was added and 0.37 g of 3-bromobenzonitrile. After 3 h the reaction mixture was poured into water and was twice subjected to extraction with dichloromethane (50 ml). The extracts were dried, concentrated and subjected to chromatography, using as eluent ether. The result has been to 0.61 g of the target compound as pale yellow foam.

IRmax(nujol): 1710, 1680, 1640, 1605 cm-1.

1H NMR (270 MHz): 3,62 (3H, s), of 3.78 (3H, s), 6.73 x to 8.0 (13H, m), 7,47 (1H, s) M. D.

P R I m e R 33. This example illustrates how to obtain (E)-methyl 2-[2-(3-pyridin-2-idoxifene)phenyl]-3-methoxypropionate (compound No. 1 of table.2).

To a stirred solution of 2.0 g of (E)-methyl 2-[2-(3-oxygenase)phenyl]-3-methods - of copropagate, obtained as described in example 1 way 15 is Idina. The resulting mixture was stirred for 3 h at 130aboutC. After cooling, it was diluted with water and was extracted twice with ether. The combined extracts were washed sequentially with an aqueous solution of sodium hydroxide, water and brine, then dried and concentrated. After chromatography using as eluent a mixture of ether and hexane were obtained 1.68 g (yield 67%) of target compound in the form of orange-yellow oily liquid.

1H NMR (270 MHz): of 3.60 (3H, s), of 3.73 (3H, s), 6,72-to 7.32 (10H, m), of 7.48 (1H, s), to 7.67 (1H, m), 8,19 (1H, m) M. D.

P R I m e R 34. This example illustrates how to obtain (E)-methyl-2-{ 2-[3-(6-chloropyridazine-3-yloxy)phenoxy] phenyl} -3 - methoxypropionate (compound N 130 table.2).

To mix the solution 2,01 g (E)-methyl 2-[2-(3-oxygenase)phenyl] -3-methods - of copropagate, obtained as described in example 1, in 30 ml of DMF was added sequentially with 0.93 g of potassium carbonate, a catalytic amount of copper chloride and 1.0 g of 3,6-dichloropyridazine. The mixture was stirred for 1 h at 95aboutC. After cooling, it was diluted with water and subjected to extraction twice with ether. The combined extracts were washed sequentially with an aqueous solution of sodium hydroxide, water, and the ether and hexane were obtained 1,71 g (yield 62%) of target compound as a yellow resin.

1H NMR (270 MHz): of 3.60 (3H, s), of 3.73 (3H, s), 6.73 x and 7.36 (N, m), 7,46 (1H, m) to 7.50 (1H, s) M. D.

The following are examples of compositions based on the compounds in accordance with the present invention, which can be used for processing of agricultural and horticultural crops. Such compositions also are the subject of the present invention. The above percentages are massive.

P R I m e R 35. Emulsifiable concentrate was prepared by mixing and subsequent mixing of the components prior to their dissolution (%).

The compound N 212 table.1 10

Bentley alcohol 30

Dodecylbenzensulfonate

calcium 5

Nonylphenolethoxylate

(13 mol of ethylene oxide) 10

The alkyl benzenes 45

P R I m e R 36. The active ingredient was dissolved in methylene chloride and the resulting solution was deposited on the granules attapulgite clay (%). After evaporation of the solvent was obtained granulated product.

The compound N 212 table.1 5

Attapulgite granulate 95

P R I m e R 37. The composition for seed treatment was obtained by grinding and mixing the three components (%). The compound N 212 table.1 50 Mineral oil 2 Kaolin 48

P R I m e R 38. Powder for spraying received the e R 39. The suspension concentrate was prepared by grinding in a ball mill components with the formation of the aqueous slurry of the crushed mixture (% ) Compound N 212 table.1 40 sodium Lignosulphonate 10 Bentonite clay 1 Water 49

The resulting composition can be used directly for spraying seed or spraying after prior dilution with water.

P R I m e R 40. Wettable powder was obtained by mixing and subsequent grinding of the components to form a homogeneous mixture (%).

The compound N 212 table.1 25

Sodium lauryl sulphate 2

Sodium lignosulphonate 5

Silicon dioxide 25

Kaolin 43

P R I m e R 41. The compounds of formula I were tested against various fungal diseases of leaves of plants. The tests were carried out as follows.

Plants were grown in John Innes Potting Compost (No. 1 or 2) in pots with a diameter of 4 see the Preparations of the tested compounds were prepared or by grinding in a ball mill with water dispersol T, or by dissolving in acetone, or a mixture of acetone and ethanol and subsequent dilution to the required concentration immediately before use. In the case of leaf diseases songs the Wu. When spraying the composition was applied to the maximum kept on leaves number. When introducing them into the soil to the root system final concentration corresponded to approximately 40 ml of the active component in the calculation of the dry soil. In the processing of cereal to compositions were added Tween 20 in an amount such that the final concentration was equal to 0.05%.

In most cases, the test compound was introduced into the soil or sprayed leaves for one or two days before infection of the plant by the pathogen. The exception was made experiments with Erysi phegraminis. In this case, the plants were infected for 24 h before processing. Infection by pathogens leaves was carried out by spraying the leaves of test plants with suspensions of spores. After infection, plants were kept in conditions favorable for disease development, as long as he appeared obvious its grounds on which it was possible to make an assessment of the extent of its development. The time between infection and assess the extent of the disease ranged from 4 to 14 days depending on disease and environmental conditions.

The degree of disease development was evaluated in points according to the following system: 4 = absence of disease; 3 = disease from traces of these plants; 0 = disease 60-100% of the untreated plants. The results are shown in table.6, standards - in table.7.

1.The method of obtaining derivatives of propanolol acid of General formula

< / BR>
where A is hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, hydroxy, phenoxy or C1-C4-alkylsulphonyl;

To - oxygen or sulfur;

X is oxygen, S(O)n, NH, NR1CH2, CHR2, CO, CH2CH2CH=CH, OCH2, (CH2)mO, CHR1O, OCH2O, S(O)nCH2, S(O)CH2O, NR1CH2, COO, OOC, SO2O COCH2O,

COCHR1O, CONH, NHCO, NHSO2COS, SCO, N=N, CH2OCO, CH2SCO, CH2NHCO, CH2ON= CH, OCH2CH2O, NR1N= CH, CH2OCONH, CH=CHCH2O, (R2)2P+CH2Q-, N(COR1), N=CH, CH(OH), CO2CH2, SCH2O, NR1CO, S(O)2NH or CONR1;

R1- C1-C4-alkyl;

R2is phenyl;

n=0,1 or 2;

m=1 to 5;

Q is a halide anion;

Z - phenyl (possibly monosubstituted C1-C6-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, phenoxy, phenyl, amino, hydroxy, 1-(C1-C4-alkoxycarbonyl)-2-(C1-C4-alkoxy)-vinyl, C1-C4-SUB>-C4-alkyl or cyano), naphthyl, chinoline, pyridinyl (possibly monosubstituted C1-C4-alkyl, C1-C4-alkoxycarbonyl, amino, halogen, nitro, C1-C4-alkylcarboxylic, di(C1-C4-alkylsulfonyl)amino, or CH(O)NH, or mono - or disubstituted by C1-C4-haloalkyl or cyano, or a disubstituted amino group and one of cyano, halogen, or C1-C4-alkoxygroup or disubstituted by nitro-group and one of cyano, halogen, di(C1-C4-alkyl)amino or C1-C4-alkoxygroup or substituted by cyano and two C1-C4-alkyl groups), pyrimidinyl (possibly monosubstituted C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkylthio, cyano, nitro, phenyl, HO2C, C1-C4-alkoxycarbonyl or C1-C4-alkylsulfonyl, or mono - or disubstituted by C1-C4-alkoxy, or mono-, di - or tizamidine halogen, or disubstituted by halogen and one of the C1-C4-alkyl or C1-C4-alkylthio or disubstituted by C1-C4-alkyl and C1-C4haloalkyl), pyrazinyl (possibly monosubstituted by halogen or cyano or disease what aminocarbonyl, or mono - or disubstituted by halogen, or disubstituted by halogen and C1-C4-alkyl), benzothiazolyl, thienyl (possibly monosubstituted by Piazolla, which itself Disaese C1-C4the alkyl and C1-C4-haloalkyl, or pyridinyl, which itself may monogamist nitro, or disubstituted by halogen), 1,2,4-triazolyl, honokalani (monosubstituted by halogen), 1,3,5-triazinyl (disubstituted by halogen or disubstituted by halogen and C1-C4-alkoxy), thiazolyl (possibly monosubstituted nitro or mono - or disubstituted by C1-C4-alkyl), benzoxazolyl, pyridinyl-N-oxide, thieno [2,3-d]pyrimidinyl, pyrrolyl (possibly monosubstituted C1-C4-alkyl), isoxazolyl (monosubstituted C1-C4-alkyl), 1,3,4-thiadiazolyl, pyrazolyl (substituted with halogen and two C1-C4-alkyl groups) or 1,2,4-triazinyl (monosubstituted by phenyl), provided that when Z is unsubstituted phenyl, and X and K are both oxygen, then A is not hydrogen;

and stereoisomers, wherein interact in the presence of base compounds of General formula

< / BR>
with a compound of General formula

< / BR>
where one of L' and L" - otdalenii the Foundation of the compounds of General formula

H

when X is oxygen, with a compound of formula ZL;

or, when X is - SO2O, with the compound of the formula ZS O2O;

or,

when X - CH2O, with the compound of the formula ZCH2L;

or,

when X IS CO, O, with the compound of the formula ZCO Hal;

or

b) interaction in the presence of a base compound of the formula

LCH

when X - OCH2with a compound of the formula ZOH;

or

when X - (C6H5)2P+CH2O-and L is a halogen, with a phosphine of the formula Z (C6H5)2P;

or

when X - OCH CO2with a compound of the formula Z CO OH;

C) when X is CH=CH, interaction in the presence of base compounds of General formula

(R1O)2--CH

where R1- C1-C6-alkyl,

with the compound of the formula Z CHO;

or

g) when X is CH= CH, the interaction of the compounds of formula I, where X - (C6H5)2P+CHR2Q-consistently with the base and a carbonyl compound of the formula Z CHO;

or

e) when X IS CONH, interaction of the compounds of General formula

< / BR>
in the presence of a base with a halogen acid of the formula Z COQ;

or

e) when X is - CH(OH), interaction of the aldehyde of General formula

< / BR>
with a Grignard reagent foam formula Z-OH in a suitable solvent in the presence of a base;

or

C) when X - OCH2the interaction of compounds of General formula

HOCH

with the compound of the formula ZL;

or

I) when X Is N=N, the interaction of the compounds of General formula

H

with the compound of the formula ZN+= NHal-;

or

K) when X - NHSO2the interaction of compounds of General formula

ClSO

with the compound of the formula

Z NH2;

where A, K and Z have the above meanings;

L - chip off the group, preferably a halogen atom and oxygen, is a HaI;

l) is a group CH3O. CH=C-(CO2CH3or half of CH2CO2CH3that can be converted into such a group by interacting with methylformate in the presence of a base and subsequent methylation in alkaline conditions.

2.The method according to p. 1, characterized in that compounds of General formula

< / BR>
where Y' is halogen,

subjected to interaction with the phenol of General formula

< / BR>
where A, X and Z have the above values,

in the presence of a base, or salt of a phenol of the specified formula in the presence of a catalyst is a copper salt or mixture of salts of copper and metallic copper.

Priorities signs:

22.01.88 when A is hydroxy, phenoxy, C1-O-, SCH2O; K is oxygen; Z is unsubstituted phenyl or substituted by halogen;

17.03.88 K - sulfur; X is oxygen, A is hydrogen, K is phenyl, Z - pyrimidinyl;

21.06.88 when A is hydrogen, X - Ph2P+CH2Br-CH2OCO; CH2NHCO, CH2SCO; K is oxygen; Z is phenyl;

08.09.88 when A is hydrogen, X - OCH2O, S(O)CH2O, CH2ON=CH, (CH2)3O, (CH2)5O, OCH2CH2O, CH2OCONH; K is oxygen, Z is phenyl.

15.09.87 - other values radicals.

 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their pharmaceutically acceptable salts and esters. In the general formula (I) X means oxygen (O) or sulfur (S) atom; R means hydrogen atom (H) or (C1-C6)-alkyl; R1 means H, -COOR, (C3-C8)-cycloalkyl or (C1-C6)-alkyl, (C2-C6)-alkenyl or (C1-C6)-alkoxyl and each of them can be unsubstituted or comprises substitutes; values of radicals R2, R3, R4, R5 and R6 are given in the invention claim. Also, invention relates to a pharmaceutical composition based on compounds of the general formula (I) and to intermediate compounds of the general formula (II) and the general formula (III) that are used for synthesis of derivatives of indane acetic acid. Proposed compounds effect on the blood glucose level and serum triglycerides level and can be used in treatment of such diseases as diabetes mellitus, obesity, hyperlipidemia and atherosclerosis.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 6 tbl, 6 sch, 251 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel hexafluoroisopropanol-substituted ether derivatives of formula (I) to their pharmaceutically acceptable salts and to esters which are capable of bonding with LXR-alpha and/or LXR-beta, as well as to pharmaceutical compositions based on said compounds. In formula (I) R1 is hydrogen, lower alkyl or halogen, one of groups R2 and R3 is hydrogen, lower alkyl or halogen, and the second of groups R2 and R3 is -O-CHR4-(CH2)m-(CHR5)n-R6. Values of R4, R5, R6 m and n are given in the formula of invention.

EFFECT: novel compounds have useful biological properties.

22 cl, 4 dwg, 102 ex

FIELD: chemistry.

SUBSTANCE: method of regioselective obtainment of 1-R1-2-R2-3-acetyl-glycerol derivative of the Formula 1 involves the following stages: Obtainment of 1-R1-3-(protective group)-glycerol of Formula 3 by adding protective group to 3rd position in 1-R1-glycerol of Formula 2; obtainment of 1-R1-2-R2-3-(protective group)-glycerol of Formula 4 by adding R2 group to 2nd position of 1-R1-3-(protective group)-glycerol of Formula 3, where R2 group is added by reaction of R2-OH with 1-R1-3-(protective group)-glycerol in the presence of aprotic organic solvent, catalyst and dehydrating medium; aprotic organic solvent is selected out of group consisting of hexane, heptane, dichloromethane, ethyl acetate, tetrahydrofuran and mixes thereof; dimethylaminopyridine is catalyst; and dicyclohexylcarbodiimide is dehydration medium; simultaneous removal of protective group and acetylation of 1-R1-2-R2-3-(protective group)-glycerol of Formula 4, where protective group removal reaction and acetylation reaction are performed using Lewis acid and acetic anhydride or using acetylation agent; Lewis acid is selected out of group including zink chloride (ZnC2), tin chloride (SnCl2), boron trifluoride diethyl ether (BF3Et2O) and mixes thereof; acetylation agent is selected out of group including acetylchloride, acetylbromide and mixes thereof, where compounds of Formulae 1-4 are racemic or optically active; R1 is palmitic acid group, R2 is linoleic acid group; P is trityl or trialkylsilyl as protective group; alkyl in trialkylsilyl is an alkylic group containing 1-5 carbon atoms, so that if the protective group is trityl then 1-R1-3-(protective group)-glycerol is obtained in the presence of pyridine solvent at 40-60°C or in the presence of nonpolar aprotic organic solvent and organic base within 0°C to room temperature range; nonpolar aprotic organic solvent is selected out of group including pyridine, dichloromethane, tetrahydrofuran, ethyl acetate and mixes thereof; organic base is selected out of group including triethylamine, tributylamine, 1,8-diazabicyclo[5,4,0]-7-undecene (DBU) and mixes thereof, and if the protective group is trialkylsilyl then 1-R1-3-(protective group)-glycerol is obtained in the presence of aprotic organic solvent and organic base within 0°C to room temperature range; aprotic organic solvent is selected out of group including dichloromethane, tetrahydrofuran, ethyl acetate, dimethylformamide and mixes thereof; and organic base is selected out of group including imidazole, triethylamine, and mixes thereof. [Formula 1] , [Formula 2] , [Formula 3] , [Formula 4] .

EFFECT: obtainment of glycerol derivative with high efficiency and output.

8 cl, 10 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula (I) where X is carboxylic acid, carboxylates, carboxylic anhydride, diglyceride, triglyceride, phospholipid, or carboxamides, or to any their pharmaceutically acceptable salt. The invention particularly refers to (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)-ethyl 2-ethyldocosa-4,7,10,13,16,19-hexanoate. The invention also refers to a food lipid composition and to a composition for diabetes, for reducing insulin, blood glucose, plasma triglyceride, for dislipidemia, for reducing blood cholesterol, body weight and for peripheral insulin resistance, including such compounds. Besides, the invention refers to methods for treating and/or preventing diabetes, dislipidemia, peripheral insulin resistance, body weight reduction and/or weight gain prevention, insulin, blood cholesterol, blood glucose and/or plasma triglyceride reduction.

EFFECT: higher clinical effectiveness.

61 cl, 4 tbl, 16 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a method of producing a compound of formula (I), where N equals 0, and values of substitutes R, R1 are given in claim 1, which involves: (i) esterification of a compound of formula (V) with an alcohol of formula , where m and m' are independently equal to 0 or 1; under the condition that both are not equal to 0 at the same time and values of A are given in claim 1, to obtain a compound of formula (III); (ii) reaction of the compound of formula (III) and a compound of formula (IV) to obtain a compound of formula (II); and (iii) reaction of the compound of formula (II) with L-CH2-C≡CH, wherein L is a leaving group, to form a compound of formula (I); intermediate compounds of formula (II), formula (III) and formula (XII) are also disclosed.

EFFECT: improved method.

15 cl, 19 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

in which m equals 1; n equals 1 or 2; t equals 0 or 1; and A is phenyl, substituted with 2 alkyl groups containing 1 or 2 carbon atoms.

EFFECT: compounds of the disclosed formula can be used as intermediate compounds for producing compounds used to treat various metabolic diseases, such as insulin resistance syndrome, diabetes, hyperlipidaemia, bacony liver, cachexia, obesity, atherosclerosis and arteriosclerosis.

17 tbl, 2 dwg, 53 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel omega-3 lipid compounds of general formula (I) or to their pharmaceutically acceptable salt, where in formula (I): R1 and R2 are similar or different and can be selected from group of substitutes, consisting of hydrogen atom, hydroxy group, C1-C7alkyl group, halogen atom, C1-C7alkoxy group, C1-C7alkylthio group, C1-C7alkoxycarbonyl group, carboxy group, aminogroup and C1-C7alkylamino group; X represents carboxylic acid or its carbonate, selected from ethylcarboxylate, methylcarboxylate, n-propylcarboxylate, isopropylcarboxylate, n-butylcarboxylate, sec-butylcarboxylate or n-hexylcarboxylate, carboxylic acid in form of triglyceride, diglyceride, 1-monoglyceride or 2-monoglyceride, or carboxamide, selected from primary carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, N-ethylcarboxamide or N,N-diethylcarboxamide; and Y stands for C16-C22 alkene with two or more double bonds, which have E- and/or Z-configuration.

EFFECT: described are pharmaceutical and lipid compositions, which contain said compounds, for application as medications, in particular, for treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, for instance, type 2 diabetes, increased levels of triglycerides and/or levels of non-HDL cholesterol, LDL cholesterol and VLDL cholesterol, hyperlipidemic condition, for instance, hypertriglyceridemia (HTG), obesity or condition of excessive body weight, fatty liver disease, for instance, non-alcoholic fatty liver disease (NAFLD) or inflammatory disease or condition.

60 cl, 3 tbl, 65 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the chemical-pharmaceutical industry, and represents using a biologically active agent for preparing a drug for metabolic disorders specified in a group consisting of insulin resistance syndrome and diabetes mellitus, including type I diabetes mellitus and type II diabetes mellitus, and obesity, wherein the agent represents a compound of formula

,

wherein n=1 or 2; m=0, 1, 2, 4 or 5; q=0; t=0 or 1; R3 represents hydrogen; A is phenyl, unsubstituted or substituted by 1 or 2 alkyls having 1 or 2 carbon atoms; and R1 is hydrogen or alkyl having 1 or 2 carbon atoms; or when R1 represents hydrogen - a pharmaceutically acceptable salt of the compound.

EFFECT: preparing the drug for metabolic disorders.

18 cl, 6 ex, 22 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula III or to its pharmaceutically acceptable salts, in which: R1 and R2 are independently selected from group, consisting of: (a) H, (b) (C2-C6)alkyl, (c) C1-C6 alkyl, interrupted by one or more groups -O-, (d) (C0-C3)alkyl-(C3-C7)cycloalkyl and (e) (CH2)nQ, where n=1-2 and where Q stands for aromatic ring system, which has from 5 to 6 ring atoms C, and Q can be independently substituted with groups up to 3 in number, selected from halogen, on condition that R1 and R2 simultaneously do not stand for H, and each alkyl of R1 and R2 can be independently substituted with one or more groups, selected from group, consisting of halogen, hydroxy, cyano, CF3 or C1-C4 alkyl, or R1 and R2 together with carbon, to which they are attached, form 3-7-member cycloalkyl or 6-member heterocycloalkyl ring, including one oxygen atom and which in case of necessity carries C1-C4 alkyl substituent, or R1 and R2 together with carbon, to which they are connected, form 3-7-member cycloalkyl ring, substituted with R20 and R21, and R20 and R21 together with carbon or carbons, to which they are connected, form 3-7-member cycloalkyl ring; R6 stands for C1-C6 alkyl; each R7 independently stands for C1-C6 alkyl; Y stands for -O-; R4 is selected from group, consisting of: (a) (C0-C3)alkyl-(C3-C7)cycloalkyl, (b) trifluoroethyl, and (c) trifluoropropyl; Z stands for phenyl or bicyclic ring system, which has 9 ring atoms, independently selected from C, N, O and S, on condition that not more than 3 ring atoms in any single ring differs from C, and said ring system can carry to 3 substituents, independently selected from group, consisting of R6, CF3 and SR6; and R5 is selected from group, consisting of NO2, NH2, F, Cl, Br, CN, SR6, S(O)2N(R7)2 and (C1-C4)alkyl, and each alkyl can be independently substituted with one or more halogens or CF3. Invention also relates to pharmaceutical composition for treatment of neurodegenerative disorder or improvement of cognitive function, containing therapeutically effective quantity of said compound; as well as to method of treatment of neurodegenerative disorder, for instance Alzheimer's disease, or improvement of cognitive function.

EFFECT: compounds act as modulators of gamma-secretase.

31 cl, 14 tbl, 3147 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound presented by formula , or their pharmaceutically acceptable salt, which can find application for treating or preventing ophthalmic diseases.

EFFECT: invention refers to the pharmaceutical compositions and methods of treating the ophthalmic diseases with the use of the above compound.

13 cl, 7 dwg, 7 tbl, 4 ex

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