The method of obtaining derivatives of n-acryloylmorpholine

 

(57) Abstract:

The inventive product-derived N-acryloylmorpholine f-ly I, where R1and R2-same or different and mean: phenyl, unsubstituted or substituted by 1-2 substituents selected from the group of halogen, C1-C4-alkyl, C - C-alkoxy, trifloromethyl or ceanography, or naphthyl or titillation; n is an integer 2 or 3; R3-C1-C4-alkoxy, or one of R3-C1-C4-alkoxy, or one of R3is hydroxy, the other C1-C4-alkoxy. Reagent 1: (R1R2)C=CH-C(O)-Z1where Z1-nucleophilic delete the group. Reagent 2: compound f-ly III, where Z2group f-IV crystals or Vice versa. The compounds possess antagonistic activity against PAF. The structure of the compounds I, II and III. 8 table.

The invention relates to the production of new derivatives of N-acryloylmorpholine, which has antagonistic activity to F and useful for the treatment of various diseases and disorders in mammals (e.g. humans) associated with imbalance in the system F.

The abbreviation "F" used in the description of the invention, means "platelet activating factor".

Natural F, according to the nature of the original tissue. The formula of the basic components F are well known. Natural F is levogyrate and its various components can be identified, for example, as l-C16:0= PAF, where alkoxygroup I-provisions F is hexadecyloxypropyl; l-C18:0= F where alkoxygroup I-provisions F is octadecylamino; or l-C18:1= =F where alkoxygroup in the I-position F is 9-(z)-octadecanoyloxy. In the above identifications of the components listed first rotation (in the above examples, - l), then the number of carbon atoms in the 1-alkoxygroup, and finally, the number of double bonds.

F has a great capacity for activation and aggregation of platelets, which got its name. However, recently it was discovered that he is potentially a critical mediator in a number of pathological processes. For example, it has hypotensive effect and increases southtransavto; he is also an active agent in promoting shock (such as endotoxin-induced shock or anaphylactic shock) and acts as a mediator of inflammatory diseases. Detected that the specified factor Yemen anaphylaxis, ulcers of the gastrointestinal tract, psoriasis and immune and renal disorders. In addition, antagonists to F can be used to prevent rejection in organ transplantation.

In this regard, in order to obtain new tools for the treatment of these pathologies, the last time do not stop the search for new antagonists to F, possesses antishock and anti-inflammatory action. In line with this, trying to find these new tools were studied various compounds known as F-antagonists. Although the chemical structure F-antagonists vary widely, and it is difficult to trace any common factor that unites all of these structures, but, in General, all compounds with F-antagonistic activity can be classified as compounds with a chemical structure F-type and compounds, chemical structure which does not apply to F type. Compounds of the present invention have a chemical structure unrelated to F-type, and in particular, are compounds containing N-acryloyldimethyl or N-acryloylmorpholine system.

Among the compounds having the structures and types of activities, similar Strunino connection inter alia [3];

alkenyl, alkanoyl or trialkane-amido-compounds [2];

- politicalcultural-pieperazinove or homopiperazine compounds disclosed, inter alia [1].

Also known derivatives of N-nicotinereplacement l, described in the patent application of Japan Coca N. Sho. 60-193966, but in this application considers only their salts and hypotensive action and there are no assumptions about whether these compounds F antagonists.

The above compounds have a structure different from the structures of the compounds of the present invention, although in some cases these compounds may have elements similar to the elements of the structure of the compounds of the present invention. In particular, none of the above compounds of the prototypes is not N-acryloylmorpholine or N-acryloylmorpholine connection.

The invention relates to a series of new derivatives of N-acryloylmorpholine and N-acryloylmorpholine high F-antagonistic activity, and in General, unexpected and high stability, even when they are orally administered. Activity of many of the compounds of the invention have significant balasubramania, including the above compounds prototypes.

The aim of the invention is to obtain a series of new derivatives of N-acryloylmorpholine.

The purpose of the invention to provide derivatives of N-acryloylmorpholine with improved antagonistic activity to F and, preferably, stable oral introduction mammals.

Received new acryloylmorpholine and acryloylmorpholine compounds having the formula (I)

where R1and R2are the same or different, and each represents a group having the formula-R5where R5present possessing phenyl group, optionally substituted by at least one Deputy, selected from the group of substituents including halogen atoms, WITH1-4alkyl nye,1-4alkoxy, triptoreline, cyano group, or R5is naftalina, thienyl group; R3is a hydrogen atom;

X is an oxygen atom;

A - 1,4-piperazine-1,4-dialnow group or hexahydro-1,4-diazepine group;

In - carbonyl group;

R4is a phenyl group, unsubstituted or substituted by at least one Deputy, selected from hydroxyl groups With1and R2are the same or different, each represents a group of formula R5.

R5is a phenyl group which may be substituted by 1-2 substituents or unsubstituted, or naftilos, thienyl group. If the specified group is substituted, the substituents are the substituents defined above. Examples of the unsubstituted groups are phenyl and naftalina (1 - or 2-naftalina) group, preferably phenyl group.

Most preferred are those compounds in which one of the groups represented by R5is a substituted phenyl group, and another group is unsubstituted phenyl group or substituted phenyl group. Even more preferably, if the group R5presented or included in the group representing R1there electrothermy Deputy (for example, methoxy group) or electron Deputy (e.g., chlorine atom); and in group R5representing or included in the group representing R2no substituents, or alkyl substituent or electroncapture Deputy.

R2represents a substituted Fe is Karami groups and atoms, which can be included in the number of the substituents of the phenyl group are:

WITH1-C4is an alkyl group, which may be groups with straight or branched chain such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl;

WITH1-C4-alkoxygroup, which can be groups with straight or branched chain, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, t-butoxy;

triptoreline group;

the atoms of halogen, such as fluorine, chlorine, bromine or iodine and preferably fluorine atoms, chlorine and bromine; and ceanography.

R3can be represented by a hydrogen atom;

X is an oxygen atom.

In may represent a carbonyl group;

R4is a phenyl group which may be unsubstituted or have at least one Deputy, selected from the group consisting of hydroxy and C1-4the alkoxy group.

The most preferred compounds of the invention are those compounds in which R4is a phenyl group having at least one1-3-alkoxy, more preferably methoxy-Deputy; and the most preferred alauli 3,4,5-trimethoxyaniline group.

Compounds of the present invention can contain one or more asymmetric carbon atoms and thus can form optical isomers having the (R) configuration or (S)-configuration. Due to the carbon-carbon double bond, these compounds can also exist as geometric isomers, i.e., (z)-isomer or (S)-isomer. Although all considered compounds are represented the same molecular formula, but also includes the individual isomers and mixtures, including the racemates. Using stereospecific synthesis of individual isomers may be obtained directly; on the other hand, upon receipt of a mixture of isomers of the individual isomers can be obtained by the method of separation.

Examples of specific compounds shown below in formulas(1 - 1) - (1 - 3), in which the substituents are defined in the corresponding table. 1 - 3 (i.e., PL. 1 corresponds to the formula (1-1), PL. 2 - the formula (1-2), etc. In the above tables the following symbols are used: Bu butyl iBu is isobutyl SBu second-Et butyl ethyl NC hexyl IU methyl Np naphthyl Ph phenyl Pn of Pentel Pr propyl Pyr phrodil Quin chinolin Tfm trifluoromethyl Thi Teenel

C=CHNN-B-H3(I-1)

C=CHNN-CO-R4(I-2)

C=CHNN-CO-R4(I-3)

Connection numbers 1-20, 1-25, 1-26, 1-28, 1-29, 1-30,

1-41, 1-45, 1-46, 1-53, 1-76, 1-83, 1-91, 1-116,

1-117, 1-118, 1-120, 1-129, 1-130, 1-133, 1-134, 1-141,

1-154, 1-155, 1-207, 1-220, 1-298, 1-300, 1-313, 1-325,

1-327, 1-342, 1-343, 1-388, 1-411, 1-412, 1-419, 1-420,

1-424, 1-425, 1-426, 1-431, 1-433, 1-441, 1-445, 1-452,

1-453, 1-454, 1-455, 1-456, 1-457, 1-458, 1-459, 1-460,

1-461, 1-462, 1-466, 1,467, 1-468, 1-469, 1-470, 1-471,

1-472, 1-473, 1-474, 1-475, 1-476, 1-477, 1-478, 1-479,

1-480, 1-481, 1-482, 1-483, 1-484, 1-485, 1-486, 1-487,

1-488, 1-489, 1-490, 1-491, 1-492, 1-496, 1-498, 1-501,

1-505, 1-507, 1-510, 1-511, 1-512, 1-513, 1-514, 1-515,

1-516, 1-517, 1-518, 1-519, 1-520, 1-521, 1-522, 1-523,

1-524, 1-525, 1-528, 1-529, 1-530, 1-531, 1-536, 1-537,

1-539, 1-541, 1-546, 1-551, 1-552, 1-553, 1-556, 1-557,

1-558, 1-559, 1-560, 1-561, 1-562, 1-563, 1-564, 1-565,

1-566, 1-567, 1-568, 1-569, 1-570, 1-571, 1-572, 1-573,

1-574, 1-580, 1-581, 1-582, 1-583, 1-584, 1-585, 1-586,

1-587, 1-588, 1-589, 1-590, 1-591, 1-592, 1-593, 1-594,

1-595, 1-596, 1-598, 1-601, 1-602, 1-603, 1-604, 1-605,

1-606, 1-607, 1-608, 1-609, 1-610, 1-611, 1-612, 1-616,

1-621, 1-622, 1-623, 1-624, 1-625, 1-626, 1-627, 1-628,

1-629, 1-630, 1-631, 1-632, 1-633, 1-634, 1-635, 1-636,

1-637, 1-638, 1-639, 1-640, 1-641, 1-642, 1-643, 1-644,

1-645, 1-646, 1-647, 1-649, 1-650, 1-651, 1-652, 1-655,

1-659, 1-660, 1-661, 1-662, 1-663, 1-664, 1-665, 1-666,

1-667, 1-668, 1-669, 1-670, 1-671, 1-672, 1-673, 1-674,

1-675, 1-676, 1-677, 1-678, 1-679, 1-680, 1-681, 1-682,

1-683, 1-684, 1-685, 1-686, 1-687, 1-688, 1-689, 1-690,

1-691, 1-692, 1-693, 1-694, 1-695, 1-696, 1-697, 1-698,

1-699, 1-700, 1-701, 1-702, 1-703, 1-704, 1-705, 1-706,

1-707, 1-708, 1-709, 1-710, 1-711, 1-712, 1-713, 1-714,

1-715, 1-716, 1-717, 1-718, 1-719, 1-720, 1-721, 1-722,

1-723, 1-724, 1-725, 1 is ylacrylic]-4- (3,4,5-trimethoxybenzoyl)piperazine;

1-419. 1-[3,3-bis(3-chlorophenyl)acryloyl] -4 -(3,4,5-trimethoxybenzoyl) piperazine;

1-424. 1-[3,3-bis(3-were)acryloyl] -4- (3,4,5-trimethoxybenzoyl)piperazine;

1-426. 1-[3,3-bis(3-trifluromethyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-453. 1-[3-(2-course)-3-(3-methoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-454. 1-[3-(2-course)-3-(4-methoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-455. 1-[3-(2-course)-3-(3-propoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-467. 1-[3-(3-course)-3-(3-methoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-468. 1-[3-(3-course)-3-(4-methoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-469. 1-[3-(3-course)-3-(3-propoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-470. 1-[3-(3-course)-3-(4-propoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-482. 1-[3-(3-course)-3-(3,4-acid)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-483 1-[3-(3-course)-3-(4-methoxy-3-propoxyphenyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-484. 1-[3-(3-course)-3-(3,4-dibromobiphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-513. 1-[3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-acryloyl]-benzoyl)piperazine;

1-557. 1-[3-(3-trifluromethyl)-3-(3-methoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-559. 1-[3-(3-triptoreline)-3-(3-propoxyphenyl)acryloyl] -4-(3,4,5-trimethoxybenzoyl)piperazine;

1-574. 1-[3-(3-trifluromethyl)-3-(3,4-acid)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-590. 1-[3-(3-were)-3-(3,4-acid)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-594. 1-[3-(3-were)-3-(4-propoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-603. 1-[3-(3-methoxy-4-propoxyphenyl) -3-phenylacrylate]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-606. 1-[3-(3,4-dibromobiphenyl)-3-phenylacrylate] -4-(3,4,5-trimetoksi)piperazine;

1-622. 1-[3-(4-ethoxy-3-methoxyphenyl)-3-phenylacrylate]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-627. 1-[3-(4-butoxy-3-methoxyphenyl)-3-phenylacrylate]-4-(3,4,5-trimetoksi)piperazine;

1-685. 1-[3-(3-methoxy-4-propoxyphenyl)-3-(3-trifluromethyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-710. 1-[3-(3-methoxy-4-propoxyphenyl)-3-(3-were)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-740. 1-[3-(3-chlorophenyl)-3-(3-methoxy-4-propoxyphenyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine;

1-743. 1-[3-chlorophenyl)-3-(4-ethoxy-3-methoxyphenyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl">

1-803. 1-/3-(2,5-Dichlorophenyl)-3/(4-methoxyphenyl)acryloyl/-4-(3,4,5-trimethoxybenzoyl)piperazine.

1-805. 1-/3-(2,5-Dichlorophenyl)-3-(4-ethoxyphenyl)acryloyl/-4-(3,4,5-trimethoxybenzoyl)piperazine.

1-858. 1-/3-(3,5-Dichlorophenyl)-3-(4-methoxyphenyl)acryloyl/-4-(3,4,5-trimethoxybenzoyl)piperazine.

1-859. 1/3-(3,5-Differenl-3-(4-ethoxyphenyl)acryloyl/-4-(3,4,5-trimethoxyphenyl)piperazine.

1-872. 1-/3-(3-forfinal)-3-(4-ethoxyphenyl)acryloyl/-4-(3,4,5-trimethoxyphenyl)piperazine.

1-873. 1-/3-(3-Cyanophenyl)-3-(4-methoxyphenyl)acryloyl/-4-(3,4,5-trimethoxybenzoyl)piperazine.

1-874. 1-/3-(3-Cyanophenyl)-3-(4-ethoxyphenyl)-acryloyl)-4-(3,4,5-trimethoxybenzoyl)piperazine.

1-877. 1-3/-(3-Chloro-5-metalfoil)-3-(4-methoxyphenyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine.

1-878. 1-3[-(3-Chloro-5-were)-3-(4-ethoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine.

Derivatives of N-acryloylmorpholine according to the present invention are produced by interaction of the compounds of formula II:

C=CZ1< / BR>
with the compound of the formula III:

Z2- B - R4< / BR>
where one of the Z1and Z2is a group Y, and the other a group of formula-A-N; "Y" is removed by nucleophilic group, the ilen deleted groups represented by Y include halogen atoms such as chlorine atoms, bromine or iodine; azide group, a lower alkoxycarbonyl groups in which the alkoxy part is 1-4, preferably 1-2 carbon atoms; such as methoxycarbonylamino and ethoxycarbonylmethoxy.

Examples of preferred methods for producing the compounds are of the following methods a and B.

Method a:

C=SON - -C=CY

- C=CA-B-R4< / BR>
In the above formulas, R1, R2, R3, R4, X, A, B and Y have the meanings defined above.

On stage a-1 carboxylic acid derivative of the formula (IV) is converted to its activated derivative of formula (V).

This activation can be carried out by standard methods, the choice of which of course depends on the nature of the obtained active derivative of the formula (V). For example, if you want to get acylhomoserine connection, it can be obtained by using the reaction of chloride of phosphorus (such as pentachloride phosphorus or trichloride phosphorus) or a derivative of sulfuric acid, such as thionyl chloride) with a carboxylic acid of formula (IV). If you want to get anilazine connection, then use the reagent sideropenia, dicarbonitrile connection, use the lowest alkylcarboxylic, such as charformat, together with an organic base.

In the above-described reactions can be used any organic base, which is commonly used in reactions of this type. Examples of such organic bases may be: trialkylamine, such as triethylamine and diisopropylethylamine; and cyclic amines, such as N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)-pyridine, N,N-dimethylaniline, 1,5-diazabicyclo[4.3.0] Nona-5-ene, 1,4-diazabicyclo [2.2.2] octane and 1,8-diazabicyclo[5.4.0]undei-7-ene (DWI).

On stage A-2 compound of formula (1) is produced by the interaction of the activated carboxylic acid derivative with the compound of the formula (VI). This reaction can be carried out in the presence or in the absence of a base, preferably in a solvent.

If activated derivative of carboxylic acid of the formula (V) is allalone, it is preferable to use the base. In this reaction can be used any base commonly used in reactions of this type. If you are using an inorganic base, for example, a carbonate of an alkali metal such as sodium carbonate or carbonate KGO metal, such as sodium hydroxide, potassium or barium, the preferred solvent is a simple ether, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amide such as dimethylformamide, dimethylacetamide or hexamethylphosphoric triamide; a sulfoxide such as dimethyl sulfoxide; NITRILES such as acetonitrile; water, or a mixture of water with any one or more of the organic solvents mentioned above. If you are using an organic base, such as triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4-(N,N-dimethylamino)pyridine, N, N-dimethylaniline, 1,5-diazabicyclo[4.3.0]Nona-5-ene, 1,4-diazabicyclo [2.2.2]octane or 1,8-diazabicyclo[5,4.0]undei-7-ene (DWI), the preferred solvent is an aromatic hydrocarbon, such as benzene, toluene or xylene; a simple ether, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; or halogenated hydrocarbons, particularly halogenated aliphatic hydrocarbons, such as methylene chloride or chloroform.

If activated derivative of carboxylic acid of the formula (V) is anilazine connection or a lower alkoxy-carbenoxolone, using the above organic is optional, the base can be used. In these reactions can be used with any standard solvent, provided that it does not adversely affect the reaction or the reagents. Examples of suitable solvents are: aromatic hydrocarbons, such as benzene, toluene, or xylene; halogenated hydrocarbons, particularly halogenated aliphatic hydrocarbons, such as methylene chloride or chloroform; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoric triamide; sulfoxidov, such as dimethyl sulfoxide; and NITRILES, such as acetonitrile.

This reaction can be conducted in a wide range of temperatures, since the reaction temperature is not critical. In General, the reaction can be carried out at 0-50aboutC, preferably at room temperature. The time of reaction may also vary widely and depends on many factors, namely the reaction temperature and the nature of the reagents. However, if the reaction is carried out at the above preferred conditions, the time of reaction is from 15 min to 1 day.

Method:

(V) C=CA-H (VIII)

C= CA-B-R4(I) where R1, R2, R3, R4, Y, X, A and b defined above.

In stage-1 of the compound of formula (VII) are obtained: first, by reacting an activated carboxylic acid derivative of the formula (V) (obtained in accordance with the description phase a-1) with the compound of the formula (VII); and then remove the formyl group, which is a Deputy at the nitrogen atom pieperazinove or homopiperazine rings "And". The reaction in the first part of this stage is basically the same and can be performed under the same conditions as the reaction stage a-2, using the same reagents as described here.

The removal of the formyl group in the second part of this stage can be carried out by processing the formyl compounds obtained in the first part of the stage, in the presence of a solvent. This can be used lubinas mixture. The reaction is carried out preferably with base: metal alkoxide such as sodium methoxide; carbonate of an alkali metal such as sodium carbonate or potassium; an alkali metal hydroxide such as sodium hydroxide or potassium; water ammonia or concentrated methanolic ammonia. Thus the nature of the used solvent is not critical and can be any suitable solvent, provided that it does not adversely affect the reactants and if he has the ability to dissolve the reagents, at least to some extent. Examples of suitable solvents can be any of the commonly used in hydrolytic reactions solvents, organic solvents such as alcohol, e.g. methanol, ethanol, or propanol; or a simple ether, such as tetrahydrofuran or dioxane; and water or a mixture of water with one or more organic solvents mentioned above.

This reaction can be conducted in a wide range of temperatures, and the precise reaction temperature of the present invention is not critical. Basically, to avoid side reactions, is suitable the temperature is going to be dependent on the source materials, the base and solvent. The time of reaction may also vary widely and depends on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, this period is from 1 to 24 hours

At stage-2, the compounds of formula (I) are obtained by reacting the compound (VIII) with the compound of the formula (IX) in the presence of base and solvent.

If not is the lowest alkalinous group, the reaction is essentially the same and is carried out in the same conditions as the reaction described in stage a-2. If is lower alkalinous group, the preferred base is an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride. Thus the nature of the used solvent is not critical, and can be used any solvent, provided that it does not adversely affect the reactants, and if he has the ability to dissolve the reagents, at least to some extent. Preferred solvents are: ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide can be isolated from the reaction mixture by standard means. For example, this can be done by adding to the reaction mixture of immiscible with water, an organic solvent followed by washing with water and distillation of the solvent. Thus obtained compound, if necessary, can be purified by standard methods such as recrystallization, pereosazhdeniya and chromatography, such as column chromatography.

Carboxylic acid derivative (IV) in which X is an oxygen atom, i.e., in other words, the compound of formula (XIII), which is one of the starting materials may be obtained in accordance with method C.

The way:

CO C

< / BR>
In the above formulas, R1, R2and R3defined above, R6is1-C6is an alkyl group, and R7is1-C6is an alkyl group or aryl group which may be optionally substituted as described above in relation to R5.

At stage s-1, the compound of formula (XII) obtained by reaction of the ketone compounds of formula (X) with Horner reagent, a compound of formula (XI). This reagent can be obtained, for example, using well known Arbuzov reaction. Specified is the nature of the applied Foundation, provided that it does not adversely affect other parts of the molecule. Examples of suitable bases include: inorganic bases such as hydrides of alkali metals (e.g. lithium hydride, sodium or potassium) and alkali metal hydroxide (e.g. sodium hydroxide, potassium or barium); organic bases such as 1,5-diazabicyclo [4.3.0] Nona-5-ene, 1,4-diazabicyclo [2.2.2]octane and 1,8-diazabicyclo [5.4.0]under-7-ene (DWI); and organic metal compounds such as utility and sitedisability.

Thus the nature of the used solvent is not critical, may be used any solvent, provided that it does not adversely affect the reactants and if he has the ability to dissolve the reagents, at least to some extent. Preferred solvents are: aromatic hydrocarbons, such as benzene, toluene or xylene; ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoric triamide; sulfoxidov, such as dimethylsulfoxide.

At stage 2, the starting material of the formula-protective group in the compound of formula (XII).

The removal of the protective group can be carried out using any known reaction of removing the protective groups of this type, for example, by treatment with acid or base. Examples of suitable acids are hydrochloric, sulfuric, phosphoric or Hydrobromic acid. In this reaction can be used any cause, provided that it does not adversely affect other parts of the compounds in the reaction mixture, however, it is preferable to use: carbonates of alkali metals such as sodium carbonate or potassium hydroxide; hydroxides of alkaline metals such as sodium hydroxide or potassium; or a concentrated methanolic ammonia. Thus the nature of the used solvent is not critical, the reaction may be used any solvent, if only it does not adversely affect the reactants and if he has the ability to dissolve the reagents, at least to some extent. Examples of solvents are water and mixtures of water with organic solvents such as the alcohols methanol, ethanol or propanol; or a simple ether (tetrahydrofuran or dioxane).

This reaction can be conducted in a wide range of reroute depending on the source materials and the used grounds. Basically, a suitable temperature is in the range from 0 to 150aboutC. the Time of reaction may also vary widely and depends on many factors, namely the reaction temperature and the nature of the reagents. However, in most cases this period is 1-10 hours

If the substituents R1and R2are different, the product is obtained as a mixture of geometric isomers. At every stage s-1 and S-2 forms (E) and (Z) can be separated using chromatography or other similar known methods.

The compounds of formula (X), which are the starting materials for this reaction are well known. Otherwise, they can be obtained, for example, by reaction of compounds of formula R1-Cho (in which R1defined above) with the compound of the formula R2-MgZ (in which R2defined above, and Z is a halogen atom) or with the compound of the formula R2-Li (in which R2defined above), or through reaction of compounds of formula R2-Cho (in which R2defined above) with the compound of the formula R1-MgZ (in which R1and Z are defined above) or with the compound of the formula R1-Li (in which R1defined above) with subsequent okelani what Finance standard methods.

In addition, using well-known reactions Friedel-mentioned compounds of formula (X) can also be obtained by reacting the compounds of formula R1H (in which R1defined above) with the compound of the formula R2-COZ (in which R2and Z are defined above), or by reacting the compounds of formula R2N (in which R2defined above) with the compound of the formula R1-Z (in which R1and Z are defined above).

As described below, method D is an alternative method for obtaining compounds of formula (XIII), in which R3is not a hydrogen atom, i.e., in other words, the compounds of formula (XVI).

Method D:

H

R2- C

In the above formulas: R1, R2and R6defined above; R3is any of the groups defined for R3except a hydrogen atom; and R1is carboxyamide group, which may or may not be the same as the group represented by R6.

In this reaction scheme, the source compound of formula (XVI) of the present invention is obtained by treatment of compounds of formula (XVI) in the presence of a solvent at -78 at 0aboutWith receipt of the anion of formula (processed at stage D-3 dehydrating agent, such as acid or phosphorus oxychloride, in the presence or absence of a solvent, after which the group of ester hydrolyzing using standard techniques.

At stages D - 1 and D -2 there are no restrictions regarding the nature of the employed solvent, provided that it does not adversely affect the reaction or the reagents. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; amides, such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; and sulfoxidov, such as dimethyl sulfoxide and sulfolane.

At stage D-1 can be used any base commonly used in this type of reactions. Examples of suitable bases include: inorganic bases such as hydrides of alkali metals (e.g. lithium hydride, sodium hydride or potassium); organic bases such as 1,5-diazabicyclo [4,3,0]Nona-5-ene, 1,4-diazabicyclo [2.2.2]octane or 1,8-disable.

At stage D-2, which is preferably carried out without intermediate allocation anion of the formula (XIV'), obtained in stage D-1, the specified anion interacts with the compound of the formula (X) with the formation of the compounds of formula (XI). This reaction is preferably carried out in the same reaction medium and under the same reaction conditions as the reaction at the stage D-1.

Stage D-3 consists of the reaction of the compounds of formula (XV) with a dehydrating agent with the formation of the target compounds of formula (XVI). This reaction can be carried out in the presence or absence of a solvent. Thus the nature of the used solvent is not decisive, in the aforementioned reaction can be used any solvent, provided that it does not adversely affect the reaction and reagents. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons, particularly halogenated aliphatic hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; esters, such as atinformation ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methylcellosolve; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; nitro compounds such as nitroethane and nitrobenzene; NITRILES such as acetonitrile and isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; sulfoxidov, such as dimethyl sulfoxide and sulfolane.

In this reaction the nature of the acid used is not a critical value and it can be any acid commonly used as a proton donor and classified as acid Branstad. Examples of suitable acids include organic acids, such as n-toluensulfonate acid and camphorsulfonic acid; and inorganic acids such as hydrochloric and sulfuric acid.

If the dehydrating agent is phosphorus oxychloride, you should use an aprotic solvent. Preferred solvents of this kind are elevations the>If the substituents R1and R2are different, the product is obtained in the form of a mixture of geometric isomers. Optionally, the Z-form and E-form can be obtained separately by using chromatography or other similar well-known methods.

Alternatively, the source compound of formula (XVI) can be obtained by using the reaction of compounds of formula (X) with the compound of the formula

Br - CH with activated zinc powder in the presence of a solvent, i.e. in accordance with the reaction of the reformed [Kametani et al. [Jakugakuzassi, 88, 911 (1968)], with subsequent de-hydration and hydrolysis in accordance with the method described above.

In the reaction of the reformed nature of the solvent is not critical provided that it does not adversely affect the reaction or the reagents. Examples of such solvents are: aliphatic hydrocarbons, such as hexane or heptane; and aromatic hydrocarbons such as benzene, toluene or xylene, preferably, aromatic hydrocarbons.

This reaction can be conducted in a wide range of temperatures and the precise reaction temperature is not critical. Basically, reaccelerate 80-100aboutC. the Time of reaction may also vary widely and depends on many factors, namely the reaction temperature of the nature of the reagents and the nature of the solvent. However, in the case of carrying out the reaction under the preferred conditions described above, this period is 1 to 24 hours, preferably 2 to 6 o'clock

In method E, below, shows an alternative method for obtaining compounds of formula (XIII), in which R2is a group-R5as defined above, i.e. the compounds of formula (XVIII):

Method E:

< / BR>
In the above formulas, R1, R3and R6have the meanings defined above, and R2is a group of the formula - R5defined above for R2.

At stage E-1 compound of the formula (XVIII) are obtained by reaction of compounds of formula (XVII) (the Heck reaction) with a compound of formula R2' - Y (where R2' and Y are defined above) in the presence of a palladium salt such as palladium acetate, in a solvent, followed by removal carboxyamide group R6above.

In this reaction the nature of the solvent is not critical and can be any suitable solvent, unless it has the second least docotoral degree. Examples of preferred solvents are NITRILES, such as acetonitrile, aromatic hydrocarbons, such as

benzene, toluene and xylene; esters such as ethyl acetate and propyl; ethers, such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; and sulfoxidov, such as dimethylsulfoxide.

The compound of formula XVII, used as starting material may be obtained from compounds of formula R1- CHO (R1defined above) using the methods described for methods C and D.

In method F, below, shows an alternative method for obtaining compounds of formula (XII) in which R3is a hydrogen atom, i.e., compounds of formula (XXI).

Method F:

C ..

In the above formulas, R1, R2, R6and Z have the meanings given above.

At stage F-1 compound of formula (XXI) are obtained from the compounds of formula (XX).

If R2is R2' (as defined above), the compound of formula (XXI) is obtained by reaction of compounds of formula (XX) with a compound F. the CSOs as chloride, bis(diphenylphosphino)ethane-Nickel (II), and in the presence of a solvent with subsequent removal carboxyamide group, R6referred to above.

In this reaction the nature of the solvent is not critical and can be used any solvent, if only it does not adversely affect the reaction and has the ability to dissolve the original connections at least to some extent. Examples of preferred solvents are: aromatic hydrocarbons, such as benzene, toluene or xylene: and ethers, such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane.

If R2is not R2'then the compound of formula (XXI) can be obtained by using the reaction of compounds of formula (XX) with the compound of the formula R5-CH= CH2(in which R5defined above) or with the compound of the formula R5- CLO (in which R5defined above) in the presence of a palladium complex, such as chloride bis(triphenylphosphine)palladium (II), and in the presence of a solvent with subsequent removal carboxyamide group 6.

The first part of the specified reaction can be conducted preferably in prisutno values and can be used in any suitable solvent, if only it does not adversely affect the reaction and has the ability to dissolve the original connections at least to some extent. The preferred solutions are: aromatic hydrocarbons, such as benzene, toluene and xylene; halogenated hydrocarbons, particularly halogenated aliphatic hydrocarbons, such as methylene chloride, ethers, such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; sulfoxidov, such as dimethylsulfoxide.

The compound of formula (XX) used in this reaction as the starting material, can be obtained by attaching the halogen atom such as chlorine or bromine, to a compound of formula (XVII), where R3is a hydrogen atom, with the subsequent removal of kaleidotrope, such as hydrogen bromide or hydrogen chloride, with the formation of a triple bond and then adding kaleidotrope, such as hydrogen bromide.

Derivatives of N-acryloylmorpholine obtained according to the present invention, have excellent antagonistic activity to F, and except for the t to be used for the treatment and prevention of various diseases and disorders, related F, such as endoxin-induced shock, anaphylactic shock, nephritis, myocardial infarction, angina, asthma, psoriasis and ulcers of the gastrointestinal tract.

In the presented subsequent experiments illustrated the biological activity of some compounds of the present invention, then examples of manufacturing products (preparative forms).

P R I m e R 1. 1-(3,3-Diphenylacetyl)-4-(3,4,5-trimethoxybenzoyl)piperazine.

4,164 g pentachloride phosphorus was added to 90 ml of methylene chloride containing 4,485 g of 3,3-diphenylacetone acid, previously cooled at 0 to 5aboutC. Then the reaction mixture was stirred for 1 h at room temperature, after which the solvent is kept at reduced pressure. The resulting residue was dissolved in 50 ml of toluene, the solvent is then again kept off under reduced pressure. The procedure of dissolution and distillation was repeated again. The result that was obtained 3,4-diphenylacetylene in the form of a white solid. Specified the crude product is directly used in the next reaction.

0,840 g of sodium bicarbonate dissolved in 15 ml of water was added and 1,214 g of 3,3-diphenylacetonitrile, obtained as described above, and the resulting mixture was stirred for 30 min at room temperature. After this time the reaction mixture was added 50 ml of methylene chloride, and then separating the organic phase and the aqueous phase from each other, the aqueous phase was extracted with methylene chloride. After that phase of methylene chloride and the methylene chloride extract were combined and washed with 10 wt.% aqueous hydrochloric acid, 5 wt.vol.% aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, respectively. Then a solution of methylene chloride was dried with anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The obtained oily residue (2.70 g) was purified by thin layer chromatography on silica gel. The obtained fractions were suirable mixture of methylene chloride and methanol (100:1) and collected, resulting in a received 2,150 g of target compound in the form of a white powder. After recrystallization of this substance from a mixture of ethyl acetate and hexane, got needle crystals white with so pl. 148-150aboutC.

NMR (Dl3270 MHz) mln.: 2,65 - of 3.80 (8H, multiplet) 3,84 (6N, C); of 3.85 (3H, s); 6,30 (1H, s); of 6.52 (2H, s); 7,2-7,5 (10H, m).

Mass spectroscopy (MS) (m/z): 486 (M+<>IR absorption spectrum l3maxcm-1: 1630, 1585.

Elemental analysis of C29H30N2ABOUT5:

Calculated: 71,59%, N 6,21%, M 5,76%

Found: 71,54%, N 6,44%, N 5,71%.

P R I m m e R 2. 1-[3,3-bis(4-methoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)- piperazine.

Repeating the procedure described in example 1, except that used 0,500 g of 3,3-bis(4-methoxyphenyl)acrylic acid, resulting in a received 0,362 g of target compound in powder form.

NMR (Dl3, 270 MHz) million dollars. (M. D.): 2,70 of 3.75 (8H, m); is 3.82 (3H, s); a-3.84 (3H, s); 3,85 (N, C); 6,14 (1H, s); is 6.54 (2H, s); 6,80 - 6,93 (4H, m); 7.18 in - 7,30 (4H, m).

MS (m/z): 546 (M+), 351 (M+-C10H11ABOUT4), 279 (M+-C17H15ABOUT3), 267 (C17H15ABOUT3), 195 (C10H11ABOUT4).

IR (l3)maxcm-1: 1625, 1605, 1585.

P R I m e R 3. 1-[3,3-bis(4-course)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)PI-perazin.

Repeating the procedure described in example 1, except that used 0,500 g of 3,3-bis(4-course) acrylic acid, resulting in a received 0,938 g of target compound in the form of a white powder.

NMR (Dl3, 270 MHz) is11ABOUT4), 279 (M+-C10H9CL2O), 275 (C15H9CL2O); 195 (C10H11ABOUT4).

IR (l3)maxcm-1: 1630; 1590.

P R I m e R 4. 1-[3,3-bis(2-thienyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)Pipera-zine.

Repeating the procedure described in example 1, except that used 0,500 g of 3,3-bis(2-thienyl)-acrylic acid, resulting in a received 0,719 g of target compound in the form of a white powder.

NMR (Dl3, 270 MHz) M. D.: 2,90 - of 2.75 (8H, m), 3,85 (N, C) 6,34 (1H, s); to 6.57 (2H, s); 7,02 (1H, DD, J = 5,13 and 3,66 Hz); was 7.08 (1H, DD, j = 5,13 and 3,66 Hz); 7,13 (1H, DD, J = 1,10 and 3,66 Hz); 7,26 (1H, DD, J = 1,10 and 3,66 Hz); to 7.32 (1H, DD, J = 5,13 and 1,10 Hz); 7,42 (1H, DD, J = 5,13 and 1,10 Hz).

MS (m/z): 498 (M+), 303 (M+-C10H11ABOUT4), 279 (M+-C11H7OS2), 219 (C11H7S2), 195 (C10H11ABOUT4).

IR (Cl3)maxcm-1: 1620, 1585.

Elemental analysis: C25H26N2O5S2:

Calculated: 60,23%; N 5,26%, N 5,62%; S 12,86%.

Found: 60,34%, N 5,43%, N 5,59%; S 12,97%.

P R I m e R 5. 1-[(Z)-3-Phenyl-3-(2-thienyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)- piperazine.

Repeated the procedure, opisanie in obtaining 1, isomer A, so pl. 144-147aboutC), resulting in a received 0,703 g of target compound in the form of a white powder.

NMR (DCl3, 270 MHz) M. D.: 2,70 of 3.75 (8H, m); a-3.84 (3H, s); 3,85 (6N, C); 6,41 (1H, s); 6,53 (2H, s), to 6.88 (1H, DD, J = 3,67 and 1,10 Hz); 6,98 (1H, DD, J = 5,13 and 3.67 Hz); 7,30 (1H, DD, J = 5,13 and 1,10 Hz); 7,40 (5H, such. the singlet).

MS (m/z): 492 (M+), 297 (M+-C10H11ABOUT4), 279 (M+-C13H9OS), 213 (C13H9OS), 195 (C10H11ABOUT4).

IR (Cl3)maxcm-1: 1620, 1585.

Elemental analysis: C27H28N2O5S:

Calculated: 65,83%; N 5,73%; N 5,69%, S 6,51%.

Found: 64,68%; N 5,97%; N 5,79%; S 6,51%.

P R I m e R 6. 1-[(E)-3-Phenyl-3-(4-pyridyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl) piperazine.

1 ml of methylene chloride containing 0,330 g diphenylphosphinite, and then 0,280 g of 1-(3,4,5-trimethoxybenzoyl)piperazine was added to 5 ml of methylene chloride containing 0,224 g (E)-3-phenyl-3-(4-pyridyl)acrylic acid (obtained in accordance with the description in obtaining 3) and 0.28 ml of triethylamine. Then the mixture was stirred for 4 h at room temperature, after which the reaction solution was diluted with 20 ml of methylene chloride. The mixture is then washed with 5 wt.vol.% Vivoli anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the oily residue (China 0,686 g) was purified using flash chromatography (instant chromatography) on silica gel. After elution with a mixture of methylene chloride and methanol (100:2 to 100:3 by volume) was obtained target compound (0,419 g) (in the form of a white powder. NMR (DCl3, 60 MHz) M. D.: 3,05 - 3,70 (8H, m); 3,84 (N, m); 6,50 (1H, s); return of 6.58 (2H, s); 7,10 - to 7.68 (7H, m); 8,45 cent to 8.85 (2H, m).

MS (m/z): 487 (M+), 292 (M+-C10H11ABOUT4), 279 (M+-C14H10NO), 208 (C14H10NO), 195 (C10H11ABOUT4).

IR (l3) maxcm-1: 1630.

P R I m e R s 7-56. Conducted following compounds were obtained from the parent compounds, which are described below in the following synthetic method:

General method of synthesis.

0.793 g (2,88 mm) diphenylphosphinite, and then 0,449 g (1,60 mm) of N-(3,4,5-trimethoxybenzoyl)piperazine was added to 7 ml of methylene chloride containing 1,60 mm corresponding derivative, 3,3-disubstituted acrylic acid (identified by the number of sample receipt on which it was received) and 0.67 ml (4,80 mm) of triethylamine. Then the reaction mixture was stirred for 3 h at whom dnim solution of sodium bicarbonate, 10 wt.vol.% aqueous hydrochloric acid and water, respectively, then the solution was dried with anhydrous sodium sulfate. The solvent is kept off, and the residue was chromatographically using liquid chromatography moderate pressure using two columns of Lobar B, which are connected in series. Then by elution with ethyl acetate to remove less polar impurities from the residue. Then after elution with a mixture of methylene chloride and methanol (from 100:1 to 100:2, by volume) was obtained target compound N-(3,3-disubstituted-acryloyl)-N-(3,4,5-trimethoxybenzoyl)Pipa - Razin, the output of which varies from 50% to 99%. If the target compound was obtained in the form of non-crystalline solids, this compound is finely ground and dried; if the connection was obtained in crystalline form, this compound is recrystallized from the appropriate solvent to obtain a sample for biological testing.

P R I m e R 7. 1-[(E)-3-(3,4-acid)cynnamoyl]-4-(3,4,5-trimethoxybenzoyl piperazine.

From [(E)-3-(3,4-acid)cinnamic acid (obtained in accordance with the description in obtaining 6) received the target compound in the form of a powder (yield 78%).

NMR (DCl3, 270 MHz) M. D.: 2,70 - 3,70 (8H, m); 3,81 (3H, /SUP>: 1625, 1585, 1460, 1420, 1330, 1130.

MS (m/z): 546 (M+), 351, 279, 267, 195.

P R I m e R 8. 1-[(Z)-3-(3,4-acid)cynnamoyl]-4-(3,4,5-trimethoxybenzoyl - yl)piperazine.

The target compound was obtained (yield 88%) of (Z)-3-(3,4-acid)cinnamic acid (obtained in accordance with the description in obtaining 7) in the form of powder.

NMR (DCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); of 3.85 (3H, s); 3,86 (IN, with); to 3.92 (3H, s); to 6.22 (1H, s); 6,55 (2H, s); to 6.80 (1H, DD, J = 8,20 and 1,46 Hz); 6,86 (1H, d, J = 8,30 Hz); 6,86 - to 6.88 (1H, m); 7,28 - 7,40 (5H, m).

IR (Cl3)maxcm-1: 1630, 1585, 1515, 1420, 1335, 1130. MS (m/z): 546 (M+), 351, 279, 276, 195.

P R I m e R 9. 4-(3,4,5-Trimethoxybenzoyl)-1-[(E)-3-(3,4,5-trimethoxyphenyl)Cinna-mail]piperazine.

The target compound in the form of crystals (yield 74%, so pl. 166-168aboutC) was obtained from (E)-3-(3,4,5-trimethoxyphenyl)cinnamic key slots (obtained in accordance with the description in obtaining 7) after recrystallization from a mixture of methylene chloride, diethyl ether and hexane.

NMR (DCl3, 270 MHz) M. D.: 2,70 - 3,70 (8H, m); of 3.78 (3H, s); 3,846 (N, C); 3,850 (3H, s); a 3.87 (3h, s); of 6.26 (1H, s); 6,47 (2H, s); 6,53 (2H, s); 7,28-7,42 (5H, m).

IR (l3)maxcm-1: 1625, 1585, 1505, 1460, 1415, 1330, 1125.

MS (m/z): 576 (M+), 381, 297, 279, 195.

P R I m e R 10. 4-(3,4,5-t is (yield 79%, so pl. 149-151aboutC) was obtained after recrystallization from a mixture of methylene chloride, diethyl ether and hexane) of (z)-3-(3,4,5-trimethoxyphenyl)cinnamic acid (obtained in accordance with the description in obtaining 11).

NMR (DCl3, 270 MHz) M. D.: 2,80-3,70 (8H, m); of 3.77 (6N, C); of 3.85 (3H, s); . 3,86 (6N, C); the 3.89 (3H, s); of 6.25 (1H, s); 6,53 (2H, s); is 6.54 (2H, s); 7,28-7,40 (5H, m).

IR (l3)maxcm-1: 1630, 1585, 1505, 1415, 1335, 1125.

P R I m e R 11. 1-[(E)-3-(3-methoxy-4-propoxyphenyl)cynnamoyl]-4-(3,4,5-trimeton - Dibenzoyl)piperazine.

From (E)-3-(3-methoxy-4-propoxyphenyl)cinnamic acid (obtained in accordance with the description in obtaining 14) was synthesized target compound in the form of a powder (yield 91%).

NMR (CDCl3, 270 MHz) M. D.: the 1.04 (3H, so J = to 7.32 Hz); of 1.88 (2H, m); 2,70-the 3.65 (8H, m); with 3.79 (3H, s); 3,84 (6N, C); of 3.85 (3H, s); 3,99 (2N, so J = 6,83 Hz); 6,24 (1H, s); 6,53 (2H, s); 6.75 in - 6,85 (3H, m); 7,27 - the 7.43 (5H, m).

IR (DCl3)maxcm-1: 1630, 1600, 1590, 1460, 1425, 1330, 1130.

MS (m/z): 574 M+, 531, 379, 295, 279, 195.

P R I m e R 12. 1-[(Z)-3-(3-methoxy-4-propoxyphenyl)cynnamoyl]-4-(3,4,5-trimeton - Dibenzoyl)piperazine.

From (Z)-3-(3-methoxy-4-propoxyphenyl)cinnamic acid (obtained in accordance with the description in obtaining 15) was synthesized target connection is 8 (3H, C); of 3.85 (3H, s); 3,86 (6N, C); 4,00 (3H, so J = 6,84 Hz); of 6.20 (1H, s); 6,55 (2H, s); is 6.78 (1H, DD; J = 8.30 and 1,46 Hz); 6,85 - to 6.95 (2H, m); 7,27 - 7,40 (5H, m).

IR (l3)maxcm-1: 1630, 1600, 1590, 1515, 1420, 1335, 1130.

MS (m/z): 574 (M+), 531, 379, 295, 279, 195.

P R I m e p 13. 1-[(E)-3-(3,4-dibromobiphenyl)cynnamoyl]-4-(3,4,5-trimedoxime-zoilus)piperazine.

From (E)-3-(3,4-dibromobiphenyl)-cinnamic acid (obtained in accordance with the description in obtaining 18) was synthesized target compound in the form of a powder (yield 87%).

NMR (CDCl3, 270 MHz) M. D.: 1,0 (3H, t, J = 7,33 Hz); of 1.05 (3H, t, J = 7,33 Hz); of 1.85 (4H, m); 2,70 - 3,70 (8H, m); 3,84 (N, C); 3,38 (6N, C); of 3.85 (3H, s); 3,88 (2H, t, J = 6,83 Hz); of 3.97 (3H, t, J = 6,84 Hz); 6,23 (1H, s); 6,53 (2H, s); to 6.80 (3H, s), 7,25 - 7,40 (5H, m).

IR (l3)maxcm-1: 1625, 1600, 1590, 1510, 1460, 1425, 1330, 1130.

MS (m/z): 602 (M+), 559, 517, 407, 323, 195.

P R I m e R 14. 1-[(Z)-3-(3,4-dibromobiphenyl)cynnamoyl)]-4-(3,4,5-trimedoxime - zoilus)piperazine.

From [(Z)-3-(3,4-dibromobiphenyl)cinnamic acid (obtained in accordance with the description in obtaining 19) was synthesized target compound in the form of a powder (yield 88%).

NMR (DCl3, 270 MHz) M. D.: a 1.01 (3H, so J = to 7.32 Hz); of 1.06 (3H, so J = to 7.32 Hz); 1.70 to 1,95 (4H, m); 2,70 - 3,70 (8H, m), 3,85 (N, C); 3,85 - to 3.92 (2H, m); 3,99 (2H, t, J = 6,84 Hz); 6"ptx2">

MS (m/z): 602 (M+), 559, 517, 407, 323, 195.

P R I m e R 15. 1-[(E)-3-(4-chlorophenyl)-3-(3,4-acid)-acryloyl] -4-(3,4,5)- trimethoxybenzoyl)piperazine.

From (E)-3-(4-chlorophenyl)-3-(3,4-acid)acrylic acid (obtained in accordance with the description in obtaining 22) synthesized the compound in the form of a powder (yield 89%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); is 3.82 (3H, s); 3,86 (N, C); are 3.90 (3H, s); 6,28 (1H, s), 6,56 (2H, s); of 6.75 (1H, Shir. C); for 6.81 (2H, Shir. C); 7,20 - 7,38 (4H, AB-like multiplet).

IR (l3)maxcm-1: 1625, 1585, 1510, 1460, 1420, 1330, 1130.

MK (m/z): 580 (M+,35CL), 385, 301, 279, 195.

P R I m e R 16. 1-[(Z)-3-(4-chlorophenyl)-3-(3,4-acid)-acryloyl] -4-(3,4,5 - trimethoxybenzoyl)piperazine.

From (Z)-3-(4-chlorophenyl)-3-(3,4-acid)acrylic acid obtained in accordance with the description in obtaining 23) was synthesized target compound in the form of powder (71% yield).

NMR (DCl3, 270 MHz) M. D.: (2,80 - 3,70) (8H, m); of 3.80 (3H, s); 3,86 (IN, with); to 3.92 (3H, s); of 6.20 (1H, s); 6,55 (2H, s); is 6.78 (1H, DD, J = 8,25 and 1.95 Hz); 6,86 (1H, d, J = 8.35 Hz); for 6.81 - 6.87 in (1H, m); 7,20 was 7.36 (4H, AB-like multiplet).

IR(l3) maxcm-1: 1635, 1595, 1515, 1465, 1425, 1335, 1135.

MS (m/z): 580 (M+,35Cl), 385, 301, 279, 195.

From (Z)-3-(3-chlorophenyl)-3-(3,4-acid)acrylic acid (obtained in accordance with the description in obtaining 26) was synthesized target compound in the form of a powder (yield 88%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); is 3.82 (3h, S); 3,86 (n, C); are 3.90 (3H, s); of 6.29 (1H, s); to 6.57 (2H, s); to 6.57 (2H, s); 6,77 (1H, Shir. C); PC 6.82 (2H, m); 7,15 - the 7.43 (4H, m).

IR (l3)maxcm-1: 1630, 1600, 1590, 1515, 1460, 1420, 1330, 1130.

MS (m/z): 580 (M+,35CL), 385, 301, 279, 195.

P R I m e R 18. 1-[(E)-3-(3-chlorophenyl)-3-(3,4-acid)-acryloyl] -4-(3,4,5 - trimethoxybenzoyl)piperazine.

From (Z)-3-(3-chlorophenyl)-3-(3,4-acid)acrylic acid (obtained in accordance with the description in obtaining 27) was synthesized target compound in the form of a powder (yield 90%).

NMR (DCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); 3,81 (3H, s); 3,86 (IN, with); to 3.92 (3H, s); to 6.22 (1H, s); 6,55 (2H, s); is 6.78 (1H, DD, J = 8.30 and of 1.95 Hz); 6,85 (1H, m); 6.87 in (1H, d, J = 8,30 Hz); 7,13 - 7,37 (4H, m).

IR (l3)maxcm-1: 1630, 1590, 1515, 1460, 1420, 1330, 1260, 1130.

MS (m/z): 580 (M+,35CL), 385, 301, 279, 195.

P R I m e R 19. 1-[(E)-3-(4-chlorophenyl)-3-(2,3-acid-acryloyl] -4 -(3,4,5 - trimethoxybenzoyl)piperazine.

From (E)-3-(4-chlorophenyl)-3-(2,3-acid)acrylic acid (obtained from the>NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); only 3.57 (3H, s); 3,86 (N, C); a 3.87 (3H, s); of 6.17 (1H, s); 6,55 (2H, s); of 6.75 (1H, DD, J = 7,81 and 1,46 Hz); 6,93 (1H, DD. J = 8.30 and 1,46 Hz);? 7.04 baby mortality (1H, t, J = 8,30 Hz); of 7.25 (2H, DM Doublet multiplets); J = 8,79 Hz); 7.29 trend (2H, DM, J = =8,79 Hz).

IR (l3)maxcm-1; 1635, 1595, 1470, 1335, 1135.

MS (m/z): 580 (M+,35Cl), 549, 301, 195.

P R I m e R 20. 1-[(Z)-3-(4-chlorophenyl)-3-(2,3-acid)-acryloyl] -4-(3,4,5 - trimethoxybenzoyl)-piperazine.

From (Z)-3-(4-chlorophenyl)-3-(2,3-acid)acrylic acid (obtained in accordance with the description in obtaining 31) was synthesized target connection with the release of 94%,

NMR (CDCl3, 270 MHz) M. D.: 2,90 - 3,70 (8H, m); 3,855 (N, C); 3,86 (N, C); 6,38 (1H, s); to 6.57 (2H, s); 6,86 (1H, DD, J = 8.30 and of 1.47 Hz); of 6.96 (1H, DD, J = 8.30 and of 1.47 Hz); 7,07 (1H, t, J = 8,30 Hz); 7,20 (2H, DM, J = 8,79 Hz); 7.29 trend (2H, DM, J = 8,79 Hz).

IR (Cl3) maxcm-1: 1630, 1585, 1460, 1420, 1330, 1125. MS (m/z): 580 (M+,35CL), 549, 301, 195.

P R I m e R 21. 1-[(Z)-3-(4-chlorophenyl)-3-(4-isobutoxy)-acryloyl] -4 -(3,4,5-tri - methoxybenzoyl)piperazine.

From (Z)-3-(4-chlorophenyl)-3-(4-isobutoxide)acrylic acid (obtained in accordance with the description in obtaining 34) was synthesized (after recrystallization from a mixture of diethyl ether and hexane) relevo the J = 6, 83 Hz); of 2.09 (1H, m); 2,80 - the 3.65 (8H, m); to 3.73 (2H, d, J = 6,34 Hz); 3,86 (N, C); of 6.26 (1H, s); 6,56 (2H, s); 6,84 (2H, DM, J = 8,30 Hz); 7,17 (2H, DM, J = 8,30 Hz); 7,22 (2H, DM, J = 8,30 Hz); 7,34 (2H, J = 8,30).

IR (l3)maxcm-1: 1625, 1605, 1590, 1510, 1460, 1425, 1330, 1175, 1130.

MS (m/z): 592 (M+,35CL), 535, 397, 313, 279, 257, 195.

P R I m e R 22. 1-[(E)-3-(4-chlorophenyl)-3-(4-isobutoxy)-acryloyl] -4-(3,4,5-tri - methoxybenzoyl)piperazine.

From (E)-3-4-chlorophenyl-3-(4-isobutoxide)acrylic acid (obtained in accordance with the description in obtaining 35) was synthesized (after recrystallization from a mixture of diethyl ether and hexane) of the target compound with a yield of 59%, and so pl. 128-129aboutC.

NMR (DCl3, 270 MHz) M. D.: 1,04 (6N, d, J = 6,84 Hz); 2,10 (1H, m); 2,70 - the 3.65 (8H, m); of 3.75 (1H, d, J = 6,35 Hz); 3,84 (6N, C); of 3.85 (3H, s); 6,18 (1H, s); is 6.54 (2H, s); to 6.88 (2H, DM, J = 8,79 Hz); 7,17 (2H, DM, J = 8,79 Hz); 7,21 (2H, DM, J = 8,30 Hz).

IR (l3)maxcm-1: 1630, 1605, 1590, 1510, 1490, 1460, 1425, 1330, 1285, 1175, 1130.

MS (m/z): 592 (M+,35CL), 535, 397, 313, 279, 257, 195.

P R I m e R 23. 1-[(Z)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)-acryloyl] -4-(3,4,5-tri-methoxybenzoyl)piperazine.

From (Z)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)-acrylic acid (obtained in accordance with the description in obtaining 38) sintesio the (8H, m); 3,86 (N, C); 3,93 (2H, t, J = 6,84 Hz); of 6.26 (1H, s); 6,56 (2H, s); 6,85 (2H, DM, J = 8,79 Hz); 7,17 (2H, DM, J = 8,79 Hz); 7,22 (2H, DM, J = 8,79 Hz); 7,34 (2H, DM, J = =8,79 Hz).

IR (l3)maxcm-1: 1630, 1605, 1590, 1510, 1460, 1330, 1130.

MS (m/z): 578 (M+,35CL), 535, 383, 299, 279, 195.

P R I m e R 24. 1-[(E)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)-acryloyl] -4-(3,4,5-tri-methoxybenzoyl)piperazine.

From (E)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)acrylic acid (obtained in accordance with the description in obtaining 39) was synthesized target compound in the form of powder with a yield of 74%.

NMR (CDCl3, 270 MHz) M. D.: of 1.06 (3H, t, J = 7,33 Hz); 1,75 - of 1.92 (2H, m); 2,80 - 3,70 (8H, m); 3,846 (6N, C); 3,850 (3H, s); 6,18 (1H, s); is 6.54 (2H, s); to 6.88 (2H, DM, J = 8,78 Hz); 7,17 (2H, DM, J = 8,78 Hz); 6,24 (2H, DM, J = 8,30 Hz); 7,30 (2H, DM, J = 8,30 Hz).

IR (l3)maxcm-1: 1630, 1605, 1590, 1510, 1460, 1420, 1330, 1130.

MS (m/z): 578 (M+,35CL), 535, 383, 299, 279, 195.

P R I m e R 25. 1-[bis(4-forfinal)acryloyl]-4-(3,4,5-trimethoxybenzoyl)Pipera-zine.

The specified connection was obtained from 3,4-bis(4-forfinal)-acrylic acid in powder form and with the release of 76%.

NMR (DCl3, 270 MHz) M. D.: 2,70 - 3,70 (8H, m), 3,85 (N, C); 6,27 (1H, s); 6,56 (2H, s); 6,97 - 7,13 (4H, m); 7,20 - 7,33 (4H, m).

IR (l3)maxcm

From [(E)-3-(4-forfinal)-3-(3,4,5-trimethoxyphenyl)-acrylic acid (obtained in accordance with the description in obtaining 42) was synthesized target connection (after recrystallization from a mixture of methylene chloride, diethyl ether and hexane) as crystals (yield 77%, so pl. 195-197aboutC).

NMR (DCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); 3,79 (6N, C); 3,86 (N, C); a 3.87 (3H, s); 6,27 (1H, s); 6,45 (2H, s); 6,56 (2H, s); 7,05-7,13 (2H, s); 7,25 - 7,33 (2N, C).

IR (l3)maxcm-1: 1625, 1585, 1505, 1460, 1415, 1330, 1125.

MS (m/z): 594 (M+), 315, 279, 195.

P R I m e R 27. 1-[(Z)-3-(4-forfinal)-3-(3,4,5-trimethoxyphenyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine.

From (Z)-3-(4-forfinal)-3-(3,4,5-trimetoksi)acrylic acid (obtained in accordance with the description in obtaining 43) was synthesized (after recrystallization from a mixture of methylene chloride and diethyl ether), the target compound in the form of crystals (yield 78%, so pl. 130-132aboutC).

NMR (DCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); of 3.77 (3H, s); of 3.85 (3H, s); 3,86 (6N, C); the 3.89 (3H, s); of 6.20 (1H, s); 6,51 (2H, s); is 6.54 (2H, s); 7,00 - to 7.09 (2H, m); 7,26 - to 7.35 (2H, m).

IR (l3)maxcm-1: 1625, 1600, 1585, 1505, 1460, 1415, 1125.

MS (m/z): 594 (M+), 315, 279, 195.

P R I m e R 28. 1-[bis-(3,4-acid is Ali from 3,3-bis(3,4-acid)acrylic acid.

NMR (DCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); 3,81 (3H, s); 3,82 (3H, s); 3,86 (N, C); 3,91 (3H, s); to 3.92 (3H, s); 6,16 (1H, s); 6,56 (2H, s); 6,80 - 6,95 (6N, m).

IR (l3)maxcm-1: 1625, 1600, 1585, 1515, 1460, 1420, 1330, 1250, 1125.

MS (m/z): 606 (M+), 411, 327, 195.

P R I m e R 29. 1-[(E)-3-(3,4-acid)-3-(4-methoxyphenyl) -acryloyl]-4-(3,4,5 - trimethoxybenzoyl)piperazine.

From (E)-3-(3,4-acid)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in obtaining 46) was synthesized target compound in the form of powder with a yield of 54%.

NMR (DCl3, 270 MHz) M. D.: 2,80-3,70 (8H, m); 3,81 (3H, s); 3,81 (3H, s); 3,85 (N, C); are 3.90 (3H, s); 6,16 (1H, s); 6,55 (2H, s); 6,76 - 6,85 (3H, m); 6.89 in (2H, DM, J = 8,78 Hz); 7,22 (2H, DM, J = 8,78 Hz).

IR (Cl3)maxcm-1: 1625, 1600, 1585, 1510, 1460, 1420, 1330, 1130.

MS(m/z): 576(M+), 381, 297, 195.

P R I m e R 30. 1-[(Z)-3-(3,4-acid)-3-(4-methoxyphenyl) -acryloyl]-4-(3,4,5 - trimethoxybenzoyl)piperazine.

From (Z)-3-(3,4-acid)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in obtaining 47) was synthesized target compound in the form of a powder (yield 73%).

NMR (CDCl3, 270 MHz) M. D.: 2,90 - 3,70 (8H, m); of 3.80 (3H, s); a 3.83 (3H, s); 3,86 (IN, with); to 3.92 (3H, s); x 6.15 (1H, s); 6,55 (2H, s); 6 MS (m/z): 576 (M+), 381, 197, 279, 195.

P R I m e R 31. 1-[Z)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acryloyl] -4-(3,4,5-tri-methoxybenzoyl)piperazine.

From (Z)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in obtaining 50) was synthesized target compound in the form of a powder (yield 85%).

NMR (CDCl3, 270 MHz) M. D.: 3,10 - 3,70 (8H, m); a 3.83 (3H, s); 3,857 (3H, s); 3,861 (6N, C); 6,32 (1H, s); return of 6.58 (2H, s); 6.87 in (2H, DM, J = =8,79 Hz); 7,13 (1H, DD, J = 8.30 and of 1.85 Hz); 7.18 in (2H, DM, J = 8,79 Hz); of 7.36 (1H, d, J = 1,95 Hz); was 7.45 (1H, d, J = 8,30 Hz).

IR (l3)maxcm-1: 1630, 1605, 1585, 1510, 1460, 1420, 1330, 1125.

MS (m/z): 584 (M+,35Cl), 389, 305, 278, 195.

P R I m e R 32. 1-[(E)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acryloyl] -4-(3,4,5-trimethoxybenzoyl)piperazine.

From (E)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in obtaining 51) was synthesized target compound in the form of a powder (yield 84%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m), 3,85 (N, C); 6,21 (1H, s); 6,24 (2H, s); make 6.90 (2H, DM, J = 8,79 Hz); 7,10 (1H, DD, J = 8.30 and of 1.95 Hz); 7.18 in (2H, DM, J = 8,79 Hz); 7,38 (1H, d, J = 1,95 Hz); 7,40 (1H, d, J = 8,30 Hz).

IR (HCl3)maxcm-1: 1630, 1605, 1585, 1510, 1460, 1420, 1330, 1130.

MS (m/z): 584 (M+,35CL), 389, who zoilus)piperazine.

From (E)-3-(3,4-acid)-3-(3-trifluromethyl) -acrylic acid (obtained in accordance with the description in obtaining 54) synthesized the target compound in the form of a powder (yield 74%).

NMR (CDCl3, 270 MHz) M. D.: 2,90 - 3,70 (8H, m); is 3.82 (3H, s); 3,848 (6N, C); 3,853 (3H, s); 3,91 (3H, s); 6,37 (1H, s); 6,77 (1H, Shir. C); 6,79 - to 6.88 (2H, m), 7,47 - of 7.60 (3H, m); 7,60 - 7,71 (1H, m).

IR (Cl3)maxcm-1: 1625, 1600, 1585, 1510, 1460, 1420, 1325, 1300, 1170, 1125.

MS (n/z): 614 (M+), 419, 335, 307, 279, 195.

P R I m e R 34.

1-[(Z)-3-(3,4-acid)-3- (3-tri-permitil)acryloyl]-4-(3,4,5-trimetoksi-benzoyl)piperazine.

From (Z)-3-(3,4-acid)-3-(3-triptoreline) -acrylic acid (obtained in accordance with the description in obtaining 55) was synthesized target compound in the form of a powder (yield 50%).

NMR (DCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); 3,81 (3H, s); of 3.85 (3H, s); 3,86 (6N, C); 3,93 (3H, s); of 6.26 (1H, s); 6,56 (2H, s); is 6.78 (1H, DD, J = 8.30 and a 1.96 Hz); 6,86 (1H, d, J = 8,30 Hz); 7,43 - 7,53 (2H, m); 7,53 - to 7.67 (2H, m).

IR (Cl3) maxcm-1: 1625, 1600, 1585, 1515, 1460, 1420, 1325, 1255, 1165, 1125.

MS (m/z): 614 (M+), 419, 335, 307, 279, 195.

P R I m e R 35. 1-[(E)-3-(3,4-acid) -3-(4-were)acryloyl]-4-(3,4,5 - trimethoxybenzoyl)piperazine.

From (E)-3-(3,4-deomali in water powder target compound (yield 89%)

NMR (CDCl3, 270 MHz) M. D.: 2,39 (3H, s); 2,80 - 3,70 (8H, m); 3,81 (3H, s); 3,848 (6N, C); 3,851 (3H, s); the 3.89 (3H, s); of 6.20 (1H, s); is 6.54 (2H, s); 6,79 (1H, Shir. C); 6,80 - of 6.90 (2H, m); 7,17 (4H, s).

IR (l3)maxcm-1: 1620, 1600, 1585, 1510, 1460, 1420, 1330, 1125.

MS (m/z): 560 (M+), 365, 281, 279, 195.

P R I m e R 36. 1-[(Z)-3-(3,4-acid)-3- (4-were-acryloyl]-4-(3,4,5 - trimethoxybenzoyl)piperazine.

From (Z)-3-(3,4-acid)-3-(4-were)-acrylic acid (obtained in accordance with the description in obtaining 59) was synthesized target compound in the form of a powder (yield 99%.

NMR (CDCl3, 270 MHz) M. D.: is 2.37 (3H, s); 2,80 - 3,70 (8H, m); of 3.80 (3H, s); of 3.85 (3H, s); 3,86 (6N, C); 3,91 (3H, s); to 6.19 (1H, s); 6,55 (2H, s); to 6.80 (1H, DD, J = 8.30 and 1,46 Hz); at 6.84 (1H, m); 6,85 (1H, d, J = 8,30 Hz); 7,14 (2H, d, J = =8,30 Hz); 7,19 (2H, d, J = 8,30 Hz).

IR (Cl3)maxcm-1: 1625, 1585, 1510, 1460, 1420, 1330, 1255, 1125.

MS (m/z): 560 (M+), 365, 281, 279, 195.

P R I m e R 37. 1-[(Z)-3-(3,4-dichlorophenyl)-3-(3-were)acryloyl] -4-(3,4,5-trim-oxybenzoyl)piperazine.

From (Z)-3-(3,4-dichlorophenyl)-3-(3-were)acrylic acid (obtained in accordance with the description in obtaining 62) was synthesized target compound in the form of a powder (yield 91%).

NMR (CDCl3, 270 MHz) M. D.: of 2.34 (3H, s); 2,90 - 3,70 ( J = 8,30 Hz).

IR (l3)maxcm-1: 1635, 1590, 1465, 1425, 1335, 1130.

MS (m/z): 568 M+,35CL 373, 289, 279, 195.

P R I m e R 38.

1-[(E)-3-(3,4-dichlorophenyl)-3-(3-methylphe - nil)acryloyl] -4-(3,4,5-trimethoxybenzoyl) piperazine.

From (E)-3-(3,4-dichlorophenyl)-3-(3-were)acrylic acid (obtained in accordance with the description in obtaining 63) was synthesized in the form of a powder (yield 92%).

NMR (DCl3, 270 MHz) M. D.: 2,35 (3H, s); 2,70 - 3,70 (8H, m); 3,84 (6N, C); of 3.85 (1H, s); 6,27 (1H, s); 6,53 (2H, s); 7,02 - 7,14 (3H, m); 7,18 - to 7.32 (2H, m); of 7.36 - 7,44 (3H, m).

IR (l3)maxcm-1: 1630, 1610, 1590, 1465, 1425, 1335, 1130.

MS (m/z): 568 (M+, 35l), 373, 289, 279, 195.

P R I m e R 39. 1-[(E)-3-(3,4-acid)-3- (3-methoxyphenyl)acryloyl]-4-(3,4,5-trimethoxybenzoyl)piperazine.

From (E)-3-(3,5-acid)-3-(3-were)acrylic acid (obtained in accordance with the description in getting 66) was synthesized target compound in the form of a powder (yield 83%).

NMR (DCl3, 270 MHz) M. D.: of 2.34 (3H, s); 2,70 - 3,70 (8H, m); 3,81 (3H, s); 3,846 (6N, C); 3,850 (3H, s); are 3.90 (3H, s); 6,21 (1H, s); is 6.54 (2H, s); 6,76 - to 6.88 (3H, m); 7,06 - 7,13 (2H, m); 7,16 - 7,30 (2H, m).

IR (Cl3)maxcm-1: 1630, 1605, 1590, 1515, 1465, 1425, 1330, 1130.

MS (m/z): 560 (M+), 365, 281, 279, 195.

From (Z)-3-(3,4-acid)-3-(3-were)acrylic acid (obtained in accordance with the description in getting 67) was synthesized target compound in the form of a powder (yield 83%).

NMR (CDCl3, 270 MHz) M. D.: of 2.34 (3H, s); 2,80 - 3,70 (8H, m); of 3.80 (3H, s); of 3.85 (3H, s). 3,86 (6N, with); to 3.92 (3H, s); of 6.20 (1H, s); 6,55 (2H, s); 6,77 - of 6.90 (3H, m); 7,06 - 7,28 (4H, m).

IR (Cl3)maxcm-1: 1630, 1600, 1590, 1515, 1465, 1425, 1330, 1260, 1130.

MS (m/z): 560 (M+), 365, 281, 279, 195.

P R I m e R 41. 1-[3,3-bis-(3-chlorophenyl)acryloyl]-4- (3,4,5-trimethoxybenzoyl)- piperazine.

From 3,3-bis(3-chlorophenyl)acrylic acid (obtained in accordance with the description in getting 110) was synthesized target compound in the form of a powder (yield 86%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); 3,86 (N, C); 6,36 (1H, c); 6,56 (2H, c); 7,10 - 7,20 (2H, m); 7,27 - 7,43 (6N, m).

IR (l3)maxcm-1: 1630, 1590, 1460, 1420, 1330, 1130.

MS (m/z): 554 (M+, 35CL), 359, 279, 275, 195.

P R I m e R 42. 1-[(Z)-3-(2-chlorophenyl)-3-(4-methoxyphenyl)acryloyl] -4-(3,4,5-trim-oxybenzoyl)piperazine.

From (Z)-3-(2-chlorophenyl)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in getting 69) was synthesized target compound in the form of a powder (yield 91%).

IR (Cl3) maxcm-1: 1630, 1605, 1585, 1510, 1460, 1420, 1330, 1130.

MS (m/z): 550 (M+,35CL), 515, 279, 271, 195.

P R I m e R 43. 1-[(Z)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)acryloyl]-4 -(3,4,5-trim-oxybenzoyl)piperazine.

From (Z)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)-acrylic acid (obtained in accordance with the description in getting 72) was synthesized target compound in the form of a powder (yield 81%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); of 3.78 (3H, s); 3,85 (N, C); 6,35 (1H, s); 6,56 (2H, s); 6,56 - 6,94 (3H, m); 7,16 - 7,40 (4H, m).

IR (l3)maxcm-1: 1625, 1600, 1585, 1460, 1420, 1330, 1125.

MS (m/z): 550 (M+,35CL), 355, 279, 271, 195.

P R I m e R 44. 1-[(E)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)acryloyl]-4 -(3,4,5-trim-oxybenzoyl)piperazine.

From (E)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)acrylic acid (obtained in accordance with the description in getting 73) was synthesized target compound in the form of a powder (yield 82%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); of 3.77 (3H, s); 3,85 (N, C); of 6.29 (1H, s); is 6.54 (2H, s); to 6.80 - 6.87 in (2H, m); 6, 90 - 6,97 (1H, m); 7,12 - 7,19 (1H, m); 7,22 - 7,37 (4H, m).

IR (l3)maxcm-1: 1630, 1600, 1585, 1460, 1420, 1330, 1125.

MS (m/z): 550 (M+, 35l), 385, 279, 271, 195.

From (Z)-3-(3-chlorophenyl)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in getting 76) was synthesized target compound in the form of a powder (yield 81%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m); a 3.83 (3H, s); 3,85 (N, C); 6,28 (1H, s); 6,56 (2H, s); 6,86 (2H, DM, J = 8,79 Hz); 7,19 (2H, DM, J = 8,79 Hz); 7,26 - 7,40 (4H, m).

IR (l3)maxcm-1: 1625, 1605, 1585, 1510, 1460, 1420, 1330, 1125.

MS (m/z): 550 (M+, 35Cl), 355, 279, 271, 195.

P R I m e R 46. 1-[(E)-3-(3-chlorophenyl)-3-(4-methoxyphenyl)acryloyl]-4 -(3,4,5-trimethoxybenzoyl)piperazine.

From (E)-3-(3-chlorophenyl)-3-(4-methoxyphenyl)acrylic acid (obtained in accordance with the description in getting 77) was synthesized target compound in the form of a powder (yield 82%).

NMR (CDCl3, 270 MHz) M. D.: 2,80 - 3,70 (8H, m), 3,85 (12 H, s); 6,21 (2H, s); 6,55 (2H, s); make 6.90 (2H, DM, J = 8,79 Hz); 7,20 (2H, DM, J = 8,79 Hz); 7,12 and 7.36 (4H, m).

IR (l3)maxcm-1: 1625, 1600, 1585, 1510, 1460, 1420, 1330, 1125.

MS (m/z): 550 (M+,35CL), 355, 379, 271, 195.

P R I m e R 47. 1-[(Z)-3-(2-naphthyl)-3-phenylacrylate]-4- (3,4,5-trimethoxybenzoyl)- piperazine.

From (Z)-3-(2-naphthyl)-3-phenylacrylate acid (obtained in accordance with the description in getting 113) was synthesized target coedine (6N, m); 7,46 - EUR 7.57 (2H, m); 7,78 - of 7.90 (4H, m).

IR (HCl3)maxcm-1: 1625, 1600, 1585, 1460, 1425, 1330, 1130.

MS (m/z): 536 (M+), 341, 279, 257, 195.

P R I m e R 48. 1-[(E)-3-(2-naphthyl)-3-phenylacrylate]-4- (3,4,5-trimethoxybenzoyl)- piperazine.

From (E)-3-(2-naphthyl)-3-phenylacrylate acid (obtained in accordance with the description in getting 114) was synthesized target compound in the form of a powder (yield 88%).

NMR (CDCl3, 270 MHz) M. D.: 2,60 - 3,70 (8H, m), 3,85 (N, C); 6,44 (1H, s); is 6.54 (2H, s); 7,30 - rate of 7.54 (8H, m); 7,71 (1H, Shir. C); 7,74 - 7,88 (3H, s).

IR (l3)maxcm-1: 1625, 1605, 1595, 1460, 1420, 1330, 1125.

MS (m/z): 536 (M+), 341, 279, 257, 195.

P R I m e R 49. 1-[(Z)-3-(3,4-dichlorophenyl)-3-(4-propoxyphenyl)acryloyl] -4-(3,4,5-tri - methoxybenzoyl)-piperazine.

From (Z)-3-(3,4-dichlorophenyl)-3-(4-propoxyphenyl)acrylic acid (obtained in accordance with the description in obtaining 80) was synthesized target compound in the form of a powder (yield 84%).

NMR (CDCl3, 270 MHz) M. D.: the 1.04 (3H, t, J = to 7.32 Hz); 1,73 - 1,90 (2H, m); 3,10 - 3,70 (8H, m); 3,86 (N, m); 3,93 (2N, so J = 6,35 Hz); of 6.31 (1H, s); return of 6.58 (2H, s); 6,86 (2H, DM, J = 8,79 Hz); 7,13 (1H, DD, J = 8.30 and 1,46); 7,17 (2H, DM, J = 8,79 Hz); of 7.36 (1H, d, J = 1,46 Hz); 7,46 (1H, d, J = 8,30 Hz).

IR (l3) maxcm-1: 1630, 1605, 1590, 1510, toxigenic)-3-phenylacrylate]-4 -(3,4,5-tri - methoxybenzoyl)piperazine.

From (E)-3-(4-ethoxy-3-methoxyphenyl)cinnamic acid (obtained in accordance with the description in getting 84) was synthesized target compound in the form of a powder (yield 93%).

NMR (CDCl3, 270 MHz) M. D.: of 1.47 (3H, t, J = 6,84 Hz); 2,50 - 3,70 (8H, m); of 3.80 (3H, s); 3,84 (N, C); of 4.11 (2H, q, J = 6,84 Hz); and 6.25 (1H, s); 6,53 (2H, s); 6,79 (1H, Shir. with); to 6.80 (2H, Shir. C); 7,27 - 7,34 (2H, m); 7,34 - 7,41 (3H, m).

IR (l3) maxcm-1: 1630, 1600, 1590, 1510, 1460, 1420, 1330, 1130.

MS (m/z): 560 (M+), 545, 365, 281, 195.

P R I m e R 51. 1-[(E)-3-(4-butoxy-3-methoxyphenyl)-3-phenylacrylate]-4 -(3,4,5-tri - methoxybenzoyl)piperazine.

From (E)-3-(4-butoxy-3-methoxyphenyl)cinnamic acid (obtained in accordance with the description in getting 88) was synthesized target compound in the form of a powder (yield 79%).

NMR (CDCl3, 270 MHz) M. D.: and 0.98 (3H, t, J = to 7.32 Hz); 1,45 is 1.58 (2H, m); 1,75 - 1,90 (2H, m); 2,60 - 3,70 (8H, m); with 3.79 (3H, s); 3,84 (N, C); 6,24 (1H, s); 6,53 (2H, s); 6,76 - 6,86 (3H, m); 7,26 - 7,34 (2H, m); 7,34 - 7,42 (3H, m).

IR (l3) maxcm-1: 1625, 1600, 1590, 1510, 1460, 1420, 1330, 1130.

MS (m/z): 588 (M+), 545, 531, 393, 309, 279, 195.

P R I m e R 52. 1-[(Z)-3-(3,4-dichlorophenyl)-3-(4-tilepanel)acryloyl]-4 -(3,4,5-trim - oxybenzoyl)piperazine.

From (Z)-3-(3,4-dichlorophenyl)-3-(4-ethylphenyl)acrylic acid (

NMR (CDCl3, 270 MHz) M. D.: a 1.25 (3H, t, J = to 7.32 Hz); to 2.67 (2H, q, J = to 7.32 Hz); 3,00 - 3,70 (8H, m); 3,86 (N, m); 6,36 (1H, s) to 6.58 (2H, s); 7,13 (1H, DD, J = 8.30 and a 1.96 Hz); 7,12 - 7,22 (4H, m); of 7.36 (1H, d, J = 1,96 Hz); 7,45 (1H, d, J = 8,30 Hz).

IR (l3)maxcm-1; 1630, 1590, 1460, 1330, 1130.

MS (m/z): 582 (M+),35CL, 387, 303, 279, 195.

P R I m e R 53. 1-[(E)-3-(4-propoxyphenyl)-acryloyl]-4-(3,4,5-trimethoxybenzoyl)- piperazine.

From (E)-3-(4-propoxyphenyl)cinnamic acid (obtained in accordance with the description in obtaining 95) was synthesized target compound in the form of a powder (yield 78%).

NMR (CDCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = 7 Hz); 1,50 - of 2.15 (2H, m); 2,80 - 3,70 (8H, m), 3,83 (N, C); a-3.84 (2H, t, J = 7 Hz); of 6.26 (1H, s); 6,56 (2H, s); 6,86 (2H, DM, J = 9 Hz); from 7.24 (2H, DM, J = 9 Hz); 7,25 - of 7.60 (5H, m).

P R I m e R 54. 1-[(E)-3-(3,4-methylenedioxyphenyl)-3-phenylacrylate]-4 -(3,4,5-trim - oxybenzoyl)piperazine.

From (E)-3-(3,4-methylenedioxyphenyl)cinnamic acid (obtained in accordance with the description in getting 96) was synthesized target compound in the form of a powder (yield 94%).

NMR (DCl3, 270 MHz) M. D.: 2,60 - 3,70 (8H, m); 3,84 (N, C); 5,98 (2H, s); 6,23 (1H, s); 6,55 (2H, s); is 6.78 (3H, s); 7,20 - of 7.60 (5H, m).

P R I m e R 55. 1-[(E)-3-(3-methoxy-4-propoxyphenyl)-3-(3-were)acryloyl]-4-(3,4,5-trimethoxybenzoyl is according to the description in obtaining 100) was synthesized target compound in the form of a powder (yield 69%).

NMR (DCl3, 270 MHz) M. D.: the 1.04 (3H, t, J = 7,33 Hz); 1,80 - of 1.95 (2H, m); of 2.34 (3H, s); 2,70 - 3,70 (8H, m); of 3.80 (3H, s); 3,85 (IN, with); to 3.99 (2H, t, J = 6,84 Hz); 6,21 (2H, s); is 6.54 (2H, s); to 6.80 (2H, Shir. C); 7,05 - 7,13 (2H, m); 7,16 - 7,30 (2H, m).

IR (l3)maxcm-1: 1630, 1600, 1590, 1510, 1460, 1425, 1330, 1260, 1130.

MS (m/z): 588 (M+), 545, 393, 309, 270, 195.

P R I m e R 56. 1-[3,3-bis(3-were)acryloyl]-4- (3,4,5-trimethoxybenzoyl]-piperazine.

From 3,4-bis(3-were)acrylic acid (obtained in accordance with the description in getting 103) was synthesized target compound in the form of a powder (yield 82%).

NMR (CDCl3, 270 MHz) M. D.: 2,34 (6N, C); 2,60 - 3,70 (8H, m); 3,84 (N, C); 6,24 (1H, s); is 6.54 (2H, s); 7,02 for 7.12 (4H, m); 7,13 - 7,29 (4H, m).

IR (l3) maxcm-1: 1630, 1605, 1590, 1460, 1425, 1330, 1130.

MS (m/z): 514 (M+,35CL), 319, 279, 235, 195.

P R I m e R 57. 1-[(E)-3,5-diphenylene-2-EN-4-enoyl]-4- (3,4,5-trimethoxybenzoyl)piperazine.

Repeated the procedure similar to that described in example 1, except that used to 0.900 g (E)-3,5-diphenylene-2-EN-4-invoi acid (obtained in accordance with the description in obtaining (105), and the results which were obtained 1,574 g of target compound in powder form.

NMR (DCl3, 270 MHz) M. D.: 3,40 - 4,00 (8H, m); a 3.83 (3H, s); 3,85 (excm-1: 1615, 1590, 1490, 1460, 1420, 1330, 1125.

Elemental analysis: C31H30N2O5.

Calculated: 72,97%; N 6,92%, N 5,49%.

Found: 72, 65%, N 6,10%, N 5.45 Per Cent.

P R I m e R 58. 1-[(2H, 4Z)-3,5-diphenylene-2,4-dienoyl]-4- (3,4,5-trimedoxime-zoilus)piperazine.

0.025 g of 10 wt.% palladium on barium sulfate) and two drops of quinoline was added to 5 ml of methanol containing 0,250 g of 1-[(E)-3,5-diphenylene-2-EN-4-enoyl] -4- (3,4,5-trimethoxybenzoyl)piperazine (obtained in accordance with the description in example 58). Then the reaction mixture at room temperature and atmospheric pressure was introduced hydrogen gas. Then the mixture was shaken for 15 h, after which the catalyst was filtered, and the solvent was removed by distillation under reduced pressure. The residue was subjected to liquid chromatography with moderate pressure using a column of Lobar Century After elution fractions with a mixture of methylene chloride and ethyl acetate in the range 3:2 to 1:3 by volume, received 0,153 g of target compound in powder form.

NMR (DCl3, 270 MHz) M. D.: 2,90 - of 3.80 (8H, m); 3,86 (3H, s); a 3.87 (6N, C); 6,38 (1H, Shir. with); to 6.58 (2H, s); of 6.61 (1H, DD, J = 12,20 and 1.95 Hz).

P R I m e R 59. 1-[3,3-bis(4-methoxyphenyl)-2-methylacrylic] -4- (3,4,5-trimetoksi - be-bis(4-methoxyphenyl)-2-methylacrylate acid (obtained according to the description in getting 108) was synthesized 0,673 g of target compound in powder form.

NMR (CDCl3, 270 MHz) M. D.: a 2.00 (3H, s); 2.95 and is - 3.45 (8H, m); of 3.80 (3H, s); 3,82 (3H, s); 3,846 (6N, C); 3,851 (3H, s); 6,53 (2H, s); 6.75 in - 7,20 (8H, m).

MS (m/z): 560 (M+); 545, 365, 281, 279, 195.

P R I m e R 60. 1-(3,3-diphenylacetyl)-4- (3,4,5-trimethoxybenzoyl)piperazine).

0,371 g pentachloride phosphorus was added in 8 ml of methylene chloride containing 0.400 g 3-phenylcarbinol acid in an ice bath. The reaction solution was stirred for 1 h at 0 to 5aboutWith, after which it are condensed by evaporation under reduced pressure. To the residue was added 10 ml of dry toluene, the mixture was evaporated to dryness under reduced pressure. The residue was dissolved in 5 ml of tetrahydrofuran, the resulting solution was added to the mixture 0,564 g N-3,4,5-trimethoxybenzylamine piperazine (obtained in accordance with the description in getting 109), 0,300 g of sodium bicarbonate, 15 ml of tetrahydrofuran and 7.5 ml of water. The reaction solution was stirred for 30 min at room temperature, and then poured into water, then was extracted twice with methylene chloride. The combined methylene chloride extracts were washed 10 wt.vol.% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride according to the pressure. The residue was chromatographically on columns using 20 g of silica gel. As a result of the factions, buervenich mixtures of methylene chloride and ethyl acetate(3:2 - 1:3), received 0,750 g of target compound in the form of crystals after recrystallization from a mixture of ethyl acetate and hexane) to T. pl. 163-165aboutC.

NMR (CDCl3, 270 MHz) M. D.: 2,17 (2N, so J = 4,76 Hz); of 2.81 (2H, t, J = 4,76 Hz); at 3.35 (2H, t, J = 4,76); TO 3.64 (2H, t, J = 4,76 Hz); 3,92 (6N, C); of 3.97 (3H, s); 6,21 (1H, s); to 6.80 (2H, s); 7,00 - 7,40 (10H, m).

MS (m/z): 522 (M+), 458, 315, 291, 231, 207.

IR (l3)maxcm-1: 1630, 1595, 1500, 1460, 1350, 1315, 1155, 1130.

Elemental analysis: C28H30N2O6S

Calculated: C 64,35%, N 5,79%, N Are 5.36%; S 6,14%.

Found: 64,60%, N 5,94%; N 5,35%, S 6,27.

P R I m e R 61. 1-(3-phenylcinnamic)-4-[3,4,5-trimetoksi(thiobenzoyl)] -piperazine.

0,836 g pentachloride phosphorus was added to 18 ml of methylene chloride containing to 0.900 g 3-phenylcarbinol acid in an ice bath. The mixture was stirred for 1 h at 0 to 5aboutC. after this time the reaction mixture is evaporated to dryness under reduced pressure, and then to the obtained residue were added 20 ml of dry toluene; after which the mixture is evaporated to dryness and the procedure repeated again R is enzoyl)piperazine, 0,674 g of sodium bicarbonate, 25 ml of tetrahydrofuran and 12.5 ml of water in an ice bath. Then the reaction mixture was stirred for 30 min at room temperature, after which it was poured into water and was extracted twice with methylene chloride. The methylene chloride extract was washed 10 wt.vol.% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and water, respectively. Then it was dried with anhydrous sodium sulfate and are condensed under reduced pressure. The residue was subjected to column chromatography using 40 g of silica gel. Then the fractions were suirable mixture of methylene chloride and ethyl acetate (3:1 by volume) and collected and the eluent was removed, resulting in a received 1,860 g of target compound in powder form.

NMR (CDCl3, 270 MHz) M. D.: 2,84 (1H, Shir.C); 3,23 (1H, Shir. C); 3,39 (1H, Shir.C); 3,51 (2H, Shir. C); at 3.69 (1H, Shir. C); 3,76 (1H, Shir.C); 3,82, 3,84 (together N, both Syngenta); to 4.17 (1H, Shir. C);6,27, 6,23 (1H, both singlets); 6,37, 6,44 (2H, both singlets); 7,20 is 7.50 (10H, m).

MS (m/z): 502 (M+), 469, 335, 295, 211, 207, 178, 167.

IR (l3)maxcm-1: 1630, 1580, 1460, 1425, 1340, 1280, 1125.

P R I m e R 62. 1-[3,3-bis(4-methoxyphenyl)acryloyl]-4-(3,4,5-trimetoksi(tibben-zoilus)piperazine.

Repeating the procedure described in item is received 0,596 g of target compound as a yellow powder.

NMR (DCl3270 MHz) M. D.: 2,96, 3,23, 3,45, 3,51, 4,20 (together, 8H, 5 cm. C); 3,82 (6N, C); 3,85 (N, C); 6,11, 6,16, (1H, both singlet); 6,38, of 6.45 (2H, both singlet); 6,80 - to 6.95 (4H, m); 7,10 - 7,30 (4H, m).

MS (m/z: 562 (M+), 529, 335, 295, 267, 227, 211.

IR (l3)maxcm-1: 1625, 1605, 1585, 1510, 1460, 1425, 1340, 1280, 1170, 1125.

Elemental analysis: C31H34N2O6S.

Calculated: 66,17%, N 6,09%; N To 4.98%; S 5,70%.

Found: 65,92%; N 6,37%; N 4,84%; S 5,65%.

P R I m e R 63. 1-[3,3-bis(4-forfinal)-4-[3,4,5-trimetoksi(thiobenzoyl)piperazine.

Repeating the procedure described in example 61, except that used 0,300 g of 3,3-bis(4-forfinal)acrylic acid, resulting in a received 0,574 g of target compound as a yellow powder.

NMR (CDCl3, 270 MHz) M. D.: 3,04, 3,25, 3,52, 3,78, 4,21 (together, 8H, 5 cm.C); 3,84 (N, C); 6,28 (1H, Shir. C); 6,45 (2H, s); 6,95 - to 7.35 (8H, m).

MS (m/z): 538 (M+), 505, 335, 295, 243, 211.

IR (l3)maxcm-1: 1630, 1600, 1580, 1505, 1460, 1425, 1340, 1125.

P R I m e R 64. 1-(3-phenylcinnamic)-4-(3,4,5-trimethoxybenzyl)piperazine.

Repeating the procedure described in example 61, except that used 0,500 g 3-phenylcarbinol acid and 0,653 g of 1-(3,4,5-trimethoxybenzyl) who MHz) M. D.: a 1.88 (2H, t, J = 5,13 Hz); of 2.25 (2H, t, J = 5,13 Hz); or 3.28 (2H, m); for 3.28 (2H, s); 3,55 (2H, t, J = 5,13 Hz); a 3.83 (3H, s); 3,84 (6N, C); 6,30 (1H, s); 6,46 (2H, s); 7,13 - 7,47 (10H, m).

MS (m/z): 462 (M+), 457, 291, 265, 207, 181.

IR (l3)maxcm-1: 1630, 1595, 1460, 1440, 1345, 1125.

P R I m e R 65. 1-[3,3-diphenyl(thiocresol)-4-[3,4,5-trimetoksi(thiobenzoyl)]PI-perazin.

A solution of 1,000 g of 1-(3-phenylcinnamic)-4-[3,4,5-trimetoksi(thiobenzoyl)piperazin (obtained as described in example 61) in 10 ml of benzene and 0,805 g of reagent Losson (containing mainly [2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphate-2,4-di - soulful] was heated in a flask under reflux for 2 hours, after this time the reaction mixture was cooled at room temperature, poured into water and was extracted twice with ethyl acetate. The extract was washed with water, dried with anhydrous sodium sulfate and concentrated by distillation under reduced pressure. The residue was purified by chromatography on silica gel (30 g), elwira with a mixture of hexane and ethyl acetate (3:1), resulting in a received 1,010 g of target compound as a yellow powder.

NMR (CDCl3, 270 MHz) M. D.: 2,86 - of 4.45 (8H, m), 3,82 (3,84 together 9H, each single.); 6,36 and 6,37 (together 2H, each a single.); 6,66 and 6,69 (together 1H, each sin, 1475, 1425, 1340, 1285, 1130.

P R I m e R 66. 1-[3,3-bis(4-methoxyphenyl)thiocresol]-4-(3,4,5-trimethoxybenzoyl - yl)piperazine.

66(a) 1-[3,3-bis(4-methoxyphenylacetyl)piperazine.

3,41 ml diphenylphosphinite and 1.99 ml of 1-formylpiperazine was added to 60 ml of methylene chloride containing 3.00 g of 3,3-bis(4-methoxyphenyl)acrylic acid and 2.94 ml of triethylamine. Then the reaction mixture was stirred for 2 h at room temperature, after which it was poured into saturated aqueous sodium bicarbonate solution and was extracted twice with methylene chloride. The combined extracts were washed with water, dried with anhydrous sodium sulfate and evaporated under reduced pressure. The residue was dissolved in 80 ml of methanol, and the resulting solution was added 40 ml of 10 wt./vol.% an aqueous solution of sodium hydroxide. The reaction mixture was stirred for 18 h at room temperature, and then poured into water, then the mixture was twice extracted with methylene chloride. The combined extracts were washed with water, dried with anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (80 g), elwira mixtures of methylene chloride and methanol (19:1 to 4:1, by volume), in resultats) M. D.: 2,08 (1H, C); 3,20 - the 3.65 (8H, m), 3,80 (6N, C); 6,13 (6N, C); 6,70 - 7,40 (8H, m).

66 (b) 1-[3,3-bis(4-methoxyphenyl)thiocresol]piperazine.

1,155 g of 1-[3,3-bis(4-methoxyphenyl)acryloyl] piperazine (obtained as described in stage (a)) was dissolved in 12 ml of benzene, the resulting solution was heated in a flask with reflux condenser for 2 h in the presence of 1,326 g of reagent Losson. After this time the reaction mixture was cooled to room temperature, after which it was poured into water, dried with anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography on silica gel (30 g), elwira mixture of methylene chloride and methanol (19:1), resulting in a received 1,177 g (1-[3,3-bis(4-methoxyphenyl)thiocresol]piperazine in the form of powder.

NMR (DCl3, 60 MHz) M. D.: 2,30 (2H, m); 2,80 (2H, m); 2,86 (1H, s(; of 3.48 (2H, m), 3,80 (6N, with); to 4.16 (2H, m); 6,50 (1H, s); 6,70 is 7.50 (8H, m).

66 (C) 1-[3,3-bis(4-methoxyphenyl)thiocresol] -4- (3,4,5-trimethoxybenzoyl)piperazine.

1,049 g of 1-[3,3-bis(4-methoxyphenyl)thiocresol]piperazine obtained in accordance with the description in stage (b) (see above) and of 0.29 ml of triethylamine were dissolved in 30 ml of methylene chloride and added of) 0.157 g of 3,4,5-trimethoxybenzylamine, klaidinti, after which it was poured into water and was extracted twice with methylene chloride. The combined extracts were washed 10 wt./vol.% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and water, respectively, after which they were dried with anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by chromatography on a column of silica gel (40 g) and using liquid chromatography with moderate pressure using a Lobar column, elwira mixtures of methylene chloride and ethyl acetate ranging from 9: 1 to 4:1, resulting in a received 1,368 g of target compound as a yellow powder.

NMR (CDCl3, 270 MHz) M. D.: 2,75 - 3,30 (2H, m); 3.40 in - 3,70 (4H, m), 3,83, 3,846 and 3,850 (together 15 N, each singlet); 6,53 and 6,55 (together 3H, each singlet); 6,80 - to 6.95 (4H, m); 7,15 - to 7.35 (4H, m).

MS (m/z: 562 (M+); 529; 455; 367.

IR (l3)maxcm-1: 1630, 1605, 1585, 1510, 1460, 1420, 1330, 1280, 1170, 1125.

P R I m e R 67. 1-[3,3-bis(4-methoxyphenyl)thiocresol]-4- (3,4,5-trimethoxy - benzoyl)piperazine.

Repeating the procedure described in example 65, except that used 0,790 g of 1-[3,3-bis(4-methoxyphenyl)- thiocresol]-4-(3,4,5-trimedoxime-zoilus)- piperazine (obtained in example 66), in the. D.: 2,99, 3,46, 3,56, 3,72, 4,27, and 4,37 (along 8H, 6 Shire. s): 3,82, a 3.83 and 3.85 (together 15 NM, each singlet); 6,39 and 6,46 (together 2H, each singlet); 6,51 and 6,55 (together 1H, each singlet); 6,80 - to 6.95 (4H, m); 7,10 - 7,37 (4H, m).

MS (m/z): 578 (M+); 545, 513, 367.

IR (l3)maxcm-1: 1605, 1580, 1510, 1460, 1425, 1335, 1280, 1170, 1125.

Elemental analysis: C31H34N20O5S2< / BR>
Calculated: 69,34%, N Of 5.92%; N 4,84%; S 11,08%.

Found: 64, 21%; N Is 6.19%; N With 4.64%; S 10,98%.

P R I m e R 68. 1-[3,3-bis(3-chlorophenyl)acryloyl]-4- (3,4-dimethoxybenzoyl)piperazine.

of 0.44 ml diphenylphosphinite and 0,545 g of 1-[3,3-bis(3-chlorophenyl)acryloyl] piperazin (obtained in accordance with the description in getting 111) was added to 10 ml of methylene chloride containing 0.25 g of 3,4-dimethoxybenzoic acid and 0.38 ml of triethylamine, and the resulting reaction mixture was stirred for 16 h at room temperature. After this time the mixture was washed 10 wt.% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and water, respectively. Then the solvent was removed by distillation under reduced pressure, and the obtained residue was purified by chromatography under moderate pressure using a column Lo is soedineniya in the form of a white powder.

NMR (CDCl3, 270 MHz) M. D.: 2,90 - 3,70 (8H, m); the 3.89 (3H, s); are 3.90 (3H, s); 6,36 (1H, s); 6,85 (1H, d, J = 7,81 Hz); 6,92 (1H, DD, J = 7,81 Hz and 1.47 Hz); to 6.95 (1H, d, J = 1,47 Hz); 7,10 - 7,20 (2H, m); 7.24 to 7,42 (6N, m).

MS (m/z): 524 (M+,35CL), 359, 275, 249, 165.

P R I m e R 69 1-[3,3-bis(3-chlorophenyl)acryloyl]-4- (4-methoxybenzoyl)piperazine.

0.25 g of p-methoxybenzylamine was added to 10 ml of methylene chloride containing 0,529 g of 1-[3,3-bis(3-chlorphenyl)acryloyl] -piperazine (obtained in accordance with the description in getting 111) and 0.41 ml of triethylamine while cooling with this ice, after which the mixture was stirred at room temperature for 1 h Then the mixture was treated and purified analogously to the description in example 68, and was received 0,682 g of target compound in powder form.

NMR (DCl3, 270 MHz) M. D.: 2,90 - 3,70 (8H, m); a 3.83 (3H, s); 6,36 (1H, s); make 6.90 (1H, DM, J = 8,79 Hz); 7,10 - 7,42 (8H, m).

MS (m/z): 494 (M+,35Cl), 359, 275, 219, 135.

Elemental analysis of C27H24N2ABOUT3CL2< / BR>
Calculated: 65,46%; N 4,99%; N 5,65%, CL 14,31%.

Found: 65,19%; N 5,12%; N 5,64%; CL 14,55%.

Using techniques similar to those described in the previous examples, were obtained the compounds shown in table. 4.

P R I m e R 87. 1-[Z-3-(2-Chlorophenyl)-3-(use of the compounds of example, obtain 180 (0.6 g) and the compound of example obtaining 179 (0,936 g) in the form of powder is 1-Z-3(2-chlorophenyl)-3-4-methoxyphenyl)acryloyl-4- (4-acetoxy-3,5-dimethoxybenzoyl)-Pipera - zine (1,072 g), so pl. 191-194aboutC.

NMR spectrum (270 MHz, DCl3) memorial plaques: of 2.34 (3H, s), 2,7-3,7 (8H, m), 3,82 (6N, (C) a 3.83 (3H, s), 6,28 (1H, s), to 6.58 (2H, s), 6.87 in (2N, IR.m., J = 8,79 Hz), 7,16 - of 7.23 (3H, m), 7,32 (1H, DV. D., J = 7,32 and to 7.32 Hz), 7,37 (1H, two DV. D., J = =7,81, 1,95 and 1.95 Hz).

Mass spectrum (m/z): 578 (M+,35CL), 536, 355, 307, 271, 181.

Infrared absorption spectrum (l3)maxcm-1: 1770, 1630, 1600, 1515, 1460, 1430, 1370, 1340, 1285, 1180, 1135.

To a solution of the obtained compound (0.5 g) in methanol (20 ml) is added a saturated aqueous solution of potassium carbonate (10 ml), the mixture was stirred for 1 h at room temperature. The reaction mixture was poured into water and extracted three times with dichloromethane. The combined extracts washed with water, dried and concentrated. The residue is purified liquid chromatography (medium pressure two columns lobar Century Faction, eluruume a mixture of ethyl acetate-methanol (19 : 1) collect and process with getting in powder form of target compound (9,464 g).

NMR spectrum (270 MHz, DCl3) memorial plaques: 3-3,7 (8H, m), 3,83 (3H, s), 3,89 (6N, (C), 5, 72 (1H, s) of 6.29 (1H, s), is 6.61 (2H, s), 6.87 in (2N, IR. m J = 9,27 Hz), 7,16-of 7.23 (3H, m), 7,31 (1H, DV. D., J = 8.3 and 8.3 Hz), 7,37 (1H, two DV. D., J = 8,3, 1,95 and 1.95 Hz).

Mass spectrum (m/z): 536 (M+), 356, 355, 271, 265, 181.

IR is R and m e R 88. 1-[Z-3-(4-Methoxyphenyl)-3-(3-triptoreline)acryloyl] -4-(3,4,5 - trimethoxybenzoyl)hexahydro-1H-1,4-di-azepine.

According to the method of example 7 was carried out by the condensation reaction of the compound of example obtaining 140 (0,516 g) with 1-(3,45-trimethoxybenzoyl)homopiperazine (0,471 g) and processing of the reaction product to produce in the form of a powder target compound (0,819 g).

NMR spectrum (270 MHz, DCl3) memorial plaques: 1,6-2,1 (2H, m), of 3.2 to 3.8 (8H, m), 3,82 (3H, s), 3,83 (3H, s), 3,85 (3H, s), 3,86 (3H, s), 6,46 (1H, ush.C) 6,55 (2H, s), for 6.81-6,92 (2H, s), 7,14-of 7.25 (2H, m), 7,4 - 7,52 (2H, m), 7,52 - 7,66 (2H, m).

Mass spectrum (m/z): 598 (M+), 403, 305, 293, 195.

Infrared absorption spectrum (l3)maxcm-1: 1630, 1610, 1590, 1510, 1465, 1420, 1320, 1180, 1130.

Obtaining 1. (E)- and (Z)-3-phenyl-3-(2-thienyl)acrylic acid.

100 ml of tetrahydrofuran containing 26,30 g triethylphosphate, was added drop by drop for 15 min at 8 to 10aboutWith 400 ml of a tetrahydrofuran suspension containing 5,63 g of the hydrate of sodium (in the form of a 55 wt.% suspension (in mineral oil) in a water bath. Then the reaction solution was stirred for 1 h at room temperature, then added 22,08 g 2-benzoylthiophene. Then the reaction mixture was heated under reflux for 21 h is Italy drove away under reduced pressure. Then 26,56 g of the obtained residue in the form of oily substance was dissolved in 450 ml of methanol, to this solution was added 150 ml of 10 wt.% an aqueous solution of sodium hydroxide. After which the mixture was stirred for 2 h at room temperature. After this time the reaction solution was poured into 500 ml of water and washed with methylene chloride. Then to bring the pH to a value of 2 to the aqueous phase was added a sufficient quantity of one of hydrochloric acid, after which the mixture was extracted with methylene chloride. The extract was dried with anhydrous sodium sulfate, the solvent is kept at reduced pressure. The residue was purified by chromatography on a column of silica gel. After elution with a mixture of methylene chloride and methanol (19: 1 by volume) was awarded first 3,415 g of the less polar isomer[(Z)-isomer, Rf : of 0.48 (silica gel, developing solvent: 24:1 mixture of methylene chloride and methanol)], and then 0,789 g other more polar isomer In [E-isomer, Rf: of 0.35 (silica gel, developing solvent: 24:1 by volume mixture of methylene chloride and methanol)].

Isomer A: Light brown crystals, so pl. 144-147aboutC.

NMR (DCl3, 90 MHz) M. D.: 6,34 (1H, s); 6,80 - 7,10 (2H, m); 7,15 - 7,50 (6N, m); to 9.93 (1H, Shir. C).

MS (m/z): 230 (M+).

2S

Calculated: 67,80%, N Of 4.38%; S 13,92%.

Found: 67,71%; N 4,12%; S 13,88%.

Isomer B: Light brown crystals, so dps, 152-155aboutC.

NMR (DCl3, 90 MHz) M. D.: 6,18 (1H, s); 6,95 - to 7.15 (1H, m); 7,15 - of 7.55 (7H, m); 10,66 (1H, Shir. C).

MS (m/z): 230 (M+).

IR (l3)maxcm-1: 1690, 1595.

Getting 2. Ethyl(E)- and (Z)-3-phenyl-3-(4-pyridyl)acrylate.

100 ml of tetrahydrofuran containing 26,92 g triethylphosphate was added drop by drop for 20 min at 8 to 10aboutC in a water bath 400 ml of a tetrahydrofuran suspension containing 5,76 g of sodium hydride (as a 55 wt.% suspension in mineral oil). Then the reaction solution was stirred for 1 h at room temperature, then added 22,00 g of 4-benzoylpyridine. Then the mixture was stirred for 3 h, the reaction solution was poured into 300 ml of water and was extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate, then the solvent is kept at reduced pressure. The obtained residue was purified by column chromatography on silica gel. After elution with mixtures of hexane and methylene chloride, in the range from 3:1 to 1:1, first received 10,047 g of the less polar isomer From (Z)-from the cation mixtures of hexane and methylene chloride in the range from 1:1 to 0:1 (by volume) received 16,603 g other more polar isomer D [(E)-isomer, Rf : of 0.55 (silica gel, developing solvent: 49:1 by volume mixture of methylene chloride and methanol)].

P R I m e R C. a Colorless oily substance.

NMR (DCl3, 90 MHz) M. D.: a 1.11 (3H, t, J = 7.5 Hz); 4,07 (2H, sq J = 7.5 Hz); 6.48 in (1H, s), 7,05 - of 7.55 (7H, m), 8,40 - of 8.90 (2H, m).

MS (m/z): 253 (M+), 208 (M+- C2H5O).

IR (l3)maxcm-1: 1720.

Elemental analysis: C16H15NO2< / BR>
Calculated: 75,87%; N 5,97; N Of 5.53%.

Found: 75,91%; N 6,26%; N 5,48%.

Isomer D: Colorless crystals, so pl. 101-102aboutC.

NMR (CDCl3, 90 MHz) M. D.: of 1.12 (3H, t, J = 7.5 Hz); of 4.05 (2H, q, J = 7.5 Hz); 6,46 (1H, s); 7,05 is 7.50 (7H, m); 8,50 cent to 8.85 (2H, m).

MS (m/z): 253 (M+), 208 (M+-C2H5O).

IR (l3)maxcm-1: 1715.

Elemental analysis: C16H15NO2< / BR>
Calculated: 75,87%; N 5,97%; N Of 5.53%.

Found: 75,86%; N 5,86%; N 5,59%.

Getting 3. (E)-3-phenyl-3-(4-pyridyl)acrylic acid.

20 ml of 10 wt. % aqueous solution of sodium hydroxide was added to 35 ml of methanol containing 3,41 g of ethyl(E)-3-phenyl-3-(4-pyridyl)acrylate (obtained as in obtaining 2), and the mixture was stirred for 1 h at room what oredom. Then the aqueous phase was added a sufficient amount of hydrochloric acid to bring the solution pH to a value of 2.8. The resulting precipitate was collected and received 2,131 g of target compound in the form of a white powder with so pl. 239-241aboutC.

NMR (hexadeuterated dimethyl sulfoxide, 90 MHz) M. D.: 6,51 (1H, s); 7,15 - of 7.55 (7H, m); 8,45 - 8,80 (2H, m).

MS (m/z: 225 (M+); 180 (M+- COOH).

IR (Mijol - brand)maxcm-1: 1697, 1625, 1602.

Get 4-103. The main synthesis of derivatives of 3,3-diphenylacetone acid according to the reaction Hake.

Was mainly carried out by the method similar to that described Heck et/J. Org., Chem, 43, 2952 (1978)], which was carried out the reaction of a combination of ester (E)-acrylic acid, substituted with a group R1in its 3-position with iodine compound having a substituted group R2. A mixture of 20 mm complex ethyl ester (E)-acrylic acid with R1in its 3-position, 30 mm Aelita represented by the General formula R2-I 4,17 ml of triethylamine, 0,270 g of palladium acetate and 8 ml of acetonitrile were placed in a tightly closed tube and heated in an oil bath at 100aboutC for 18 h Then the mixture was left to cool, after which Ishenim aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride. The organic phase was dried and are condensed by evaporation under reduced pressure. The residue was subjected to flash chromatography on a column of silica gel (400 Tueg mesh, 400 g) and liquid chromatography with moderate pressure using a Lobar column (Type Si-60). After elution with mixtures of methylene chloride, diethyl ether and hexane in ratios ranging from 1:1:5 to 1:1:4 (received separately)-isomer and the (Z)-isomer 3,3-disubstituted ethyl acrylate. In the case when received two isomers, each of them is mentioned in a separate receipt, and the isomer, suirvey in chromatographic procedure previously indicated in the pair of receiving the first. As eluent for the separation of isomers of compounds of making 32/33 and 36/37 used toluene. Selected complicated ethyl ester (E)- or (Z)-3,3-diphenylacetone acid (4 mm) was dissolved in a mixture of 12 ml of dioxane and 12 ml of methanol was added 5 ml (10 wt./vol.%) an aqueous solution of sodium hydroxide in order to perform hydrolysis. The reaction mixture was stirred at room temperature for 18 h, after which the solvent drove away. The residue was diluted with 20 ml water and washed with ethyl acetate. Then to bring the pH to a value of 2 to the aqueous phase was added to our existing, the United methylene chloride extracts were washed with water and then dried with anhydrous sodium sulfate. The result that was obtained 3,3-disubstituted acrylic acid in the form of solids. Listed below are systematized the results.

Compounds of ester obtained in the receiving 96 and 97, can not be separated as described above, the separation may be carried out using the following procedure.

The mixture of compounds was obtained 96 and 97 hydrolyzed as described above. Then thus obtained mixture of acidic compounds were washed with methylene chloride, and the insoluble substance was recrystallized from a mixture of diethyl ether and tetrahydrofuran, resulting in the received connection is getting 96 (E)-isomer). Methylenchloride washing are condensed by distillation under reduced pressure, and then recrystallized from a mixture of methylene chloride and hexane, resulting in the received connection is getting 97 (Z-isomer).

Getting 4. Ethyl(E)-3-(3,4-acid)cinnamate.

The compound was obtained as an oily substance with a yield of 14%.

NMR (CDCl3, 270 MHz) M. D.: 1,10 (3H, t, J = to 7.32 Hz); 3,82 (3H, s); 3,88 (3H, s); Android 4.04 (2H, square, J = to 7.32 Hz); 6,32 (1H, s); 6,74 - 6,84 (2H, m); 6.89 in (1H, Shir. C); 7,16 - of 7.25 (2H, m); 7,34 - 7,42 (2H, m).

IR (l3)maxcm-1

The compound was obtained after recrystallization from a mixture of diethyl ether and hexane) as crystals with a yield of 21%, and so pl. 93 - 95aboutC.

NMR (CDl3, 270 MHz) M. D.: of 1.16 (3H, t, J = to 7.32 Hz); 3,81 (3H, s); to 3.92 (3H, s); 4.09 to (2H, q, J = to 7.32 Hz); of 6.29 (1H, s); 6,72 (1H, d, J = 1,95 Hz); PC 6.82 (1H, DD, J = 8.30 and of 1.95 Hz); to 6.88 (1H, d, J = 8,30 Hz); 7,30 - 7,14 (5H, m).

IR (l3)maxcm-1: 1710, 1605, 1585, 1465, 1445, 1160, 1135.

MS (m/z): 312 (M+), 297, 283, 267, 240.

Getting 6. (E)-3-(3,4-acid)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 98%, and so pl. 178 - 181aboutC.

NMR (DCl3, 270 MHz) M. D.: 3,81 (3H, s); 3,88 (3H, s); 6,28 (1H, s); 6.75 in - 6,83 (2H, m); 6,86 (1H, Shir. C); 7,17 - of 7.25 (2H, m); 7,33 - the 7.43 (3H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1595, 1515, 1260, 1135.

MS (m/z): 284 (M+), 269, 267, 239.

Getting 7. (Z)-3-(3,4-acid)cinnamic acid).

The compound was obtained as crystals with so pl. 162-164aboutAfter recrystallization from a mixture of diethyl ether and hexane (yield (99%).

NMR (DCl3, 270 MHz) M. D.: of 3.80 (3H, s); to 3.92 (3H, s); of 6.26 (1H, s); of 6.75 (1H, d, J = 1,95 Hz); to 6.80 (1H, DD, J = 8.30 and of 1.95 Hz); 6.87 in SS="ptx2">

MS (m/z): 284 (M+), 269, 267, 239.

Getting 8. Ethyl (E)-3-(3,4,5-trimethoxyphenyl)cinnamate.

The compound was obtained as crystals (after recrystallization from a mixture of diethyl ether, methylene chloride and hexane) to yield 19%, and so pl. 119-121aboutC.

NMR (CDCl3, 270 MHz) M. D.: a 1.11 (3H, t, J = to 7.32 Hz); of 3.77 (6N, C); a 3.87 (3H, s); of 4.05 (2H, q, J = to 7.32 Hz); 6,32 (2H, s); 6,51 (2H, s); 7.18 in amounts to 2.24 (2H, m); 7,35 - 7,41 (3H, m).

IR (l3)maxcm-1: 1710, 1615, 1580, 1500, 1460, 1415, 1160, 1125.

MS (m/z): 342 (M+), 327, 313, 199, 297.

9. Ethyl(Z)-3-(3,4,5-trimethoxyphenyl)cinnamate.

The compound was obtained as crystals (recrystallization at the expense of methylene chloride and diethyl ether) to yield 35%, and so pl. 96-98aboutC.

NMR (DCl3; 270 MHz) memorial plaques: to 1.14 (3H, t, J = 7,33 Hz); 3,80 (6N, C); are 3.90 (3H, s); 4,08 (2H, q, J = 7,33 Hz); 6,32 (1H, s); to 6.43 (2H, s); 7,31 - 7,40 (5H, m).

IR (l3)maxcm-1: 1710, 1610, 1585, 1500, 1460, 1410, 1300, 1170, 1125.

MS (m/z): 342 (M+), 327, 313, 299, 297.

10. (E)-3-(3,4,5-trimethoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of diethyl ether and methylene chloride) to yield 100% so pl. 202-206what="ptx2">

IR (KBR)maxcm-1: 2400 - 3400 (Shir.), 1688, 1610, 1578, 1502, 1241, 1200, 1129.

MS (m/z): 314 (M+), 299.

Receipt 11. (Z)-3-(3,4,5-trimethoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 100% (so pl. 203-205aboutC).

NMR (CDCl3, 270 MHz) M. D.: 3,78 (6N, C); 3,91 (3H, s); 6,30 (1H, s); 6,44 (2H, s); 7,28 - the 7.43 (5H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1610, 1580, 1500, 1460, 1410, 1365, 1125.

MS (m/z): 314 (M+), 299.

Getting 12. Ethyl(E)-3-(3-methoxy-4-propoxyphenyl)cinnamate.

The compound was obtained as crystals (recrystallization from hexane) to yield 24% (so pl. 66-68aboutC).

NMR (DCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = to 7.32 Hz), 1,10 (3H, t, J = 7,33 Hz); 1,80 - of 1.95 (2H, m); 3,81 (3H, s); 3,98 (2H, t, J = 6,84 Hz); a 4.03 (2H, q, J = 7,33 Hz); of 6.31 (1H, s); 6,77 (1H, s); is 6.78 (1H, s); 6.89 in (1H, s); 7,16 - of 7.25 (2H, m); 7,35 - 7,45 (3H, m).

IR (Cl3)maxcm-1: 1710, 1600, 1520, 1470, 1375, 1260, 1160, 1140.

MS (m/z): 340 (M+), 298, 269, 253, 226.

13. Ethyl(Z)-3-(3-methoxy-4-propoxyphenyl)cinnamate.

The compound was obtained as an oily substance with a yield of 37%.

NMR (CDCl3, of 2.72 (1H, d, J = 1,95 Hz); is 6.78 (1H, DD, J = 8.30 and of 1.95 Hz); 6.87 in (1H, d, J = 8,30 Hz); 7,30 - 7,42 (5H, m).

IR (l3)maxcm-1: 1710, 1610, 1515, 1470, 1375, 1260, 1170, 1140.

MS (m/z): 340 (M+), 298, 269, 253, 226.

Getting 14. (E)-3-(3-methoxy-4-propoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 94% (so pl. 147-150aboutC).

NMR (DCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = 7,33 Hz); 1,75 - 2,00 (2H, m); with 3.79 (2H, s); 3,98 (2H, t, J = 6,84 Hz); 6,28 (1H, s); 6.73 x - to 6.80 (2H, m); 6,85 (1H, Shir. C); 7,15-of 7.25 (2H, m); 7,33 - 7,40 (3H, m).

IR (Cl3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1610, 1595, 1580, 1510, 1465, 1260, 1180, 1135.

MS (m/z): 312 (M+), 270, 253, 225.

Get 15. (Z)-3-(3-methoxy-4-propoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 93% (so pl. 139-142aboutC).

NMR (DCl3, 270 MHz) M. D.: of 1.06 (3H, t, J = 7,33 Hz); 1,80 - 2,00 (2H, m); with 3.79 (3H, s); 4,01 (2H, t, J = 6,84 Hz); 6,24 (1H, s); 6,29 - 6,79 (2H, m); 6,85 (1H, DD, J = 8,33 and 1.47 Hz); 7,25 was 7.45 (5H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1600, 1575, 1510, 1465, 1445, 1410, 1250, 1130.

MS (m/z): 312 (M+), 270, 253, 225.

Policer> NMR (DCl3, 270 MHz) M. D.: a 1.01 (3H, t, J = 7,33, Hz); of 1.03 (3H, t, J = 7,33 Hz); of 1.10 (3H, t, J = 7,33 Hz); 1.70 to 1,95 (4H, m), 3,90 (2H, t, J = 6,83 Hz); of 3.96 (2H, t, J = 6,83 Hz); a 4.03 (2H, q, J = 7,33 Hz); 6,30 (1H, s); 6,72 - to 6.80 (2H, m); 6.90 to (1H, Shir. C); 7,15 - of 7.25 (2H, m); 7,30 was 7.45 (3H, m).

IR (l3)maxcm-1: 1705, 1595, 1510, 1470, 1370, 1260, 1160, 1130.

MS (m/z): 368 (M+) 326, 323, 284.

Getting 17. Ethyl(Z)-3-(3,4-dibromobiphenyl)cinnamate.

Got oily substance with a yield of 25%.

NMR (CDCl3, 270 MHz) M. D.: a 1.00 (3H, t, J = to 7.32 Hz); of 1.06 (3H, t, J = to 7.32 Hz); to 1.15 (3H, t, J = to 7.32 Hz); 1.70 to 1,95 (4H, m); the 3.89 (2H, t, J = 6,84 Hz); 4,00 (2H, t, J = 6,84 Hz); 4,08 (2H, q, J = to 7.32 Hz); of 6.26 (1H, s); of 6.73 (1H, d, J = 1,95 Hz); 6,77 (1H, DD, J = 8.30 and of 1.95 Hz); 6,86 (1H, d, J = 8,30 Hz); 7,25 - 7,40 (5H, m).

IR (l3)maxcm-1: 1710, 1605, 1510, 1470, 1445, 1370, 1260, 1160, 1130.

MS (m/z): 368 (M+), 326, 323, 284.

Getting 18. (E)-3-(3,4-dichlorophenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 92% (so pl. 102-103aboutC).

NMR (DCl3, 270 MHz) M. D.: a 1.00 (3H, t, 1 = to 7.32 Hz); of 1.03 (3H, t, J = to 7.32 Hz); 1.70 to 1,95 (4H, m); the 3.89 (2H, t, J = 6,83 Hz); of 3.96 (2H, t, J = 6,84 Hz); of 6.26 (1H, s); 6,74 (1H, DD, J = 8.30 and a 1.96 Hz); is 6.78 (1H, d, J = 8,30 Hz); 6,86 (1H, d, J = 1,96 Hz); 7,15 - of 7.25 (2H, m); 7,30 - 7,40 (3H, m 340 (M+), 298, 256, 239.

Getting 19. (Z)-3-(3,4-dibromobiphenyl) cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 94% (so pl. 120-123aboutC).

NMR (CDCl3, 270 MHz) M. D.: a 1.00 (3H, t, J = 7,33 Hz); of 1.06 (3H, t, J = to 7.32 Hz); 1.70 to 1,95 (4H, m); the 3.89 (2H, t, J = 6,84 Hz); 4,00 (2H, t, J = 6,84 Hz); 6,23 (1H, s); 6.73 x - to 6.80 (2H, m); 6,83 - 6,87 (1H, m); 7,25 was 7.45 (5H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1610, 1515, 1260, 1135.

MS (m/z): 340 (M+), 298, 256, 239.

20. Ethyl(E)-3-(4-chlorophenyl)-3- (3,4-acid)acrylate.

The compound was obtained as crystals (after recrystallization from a mixture of diethyl ether and hexane) to yield 14% (so pl. 83-84aboutC).

NMR (DCl3, 270 MHz) memorial plaques: to 1.15 (3H, t, J = to 7.32 Hz); of 3.84 (3H, s); the 3.89 (3H, s); 4,06 (2H, q, J = to 7.32 Hz); of 6.31 (1H, s); 6,76 (1H, DD, J = 8,79 and 1.95 Hz); to 6.80 (1H, d, J = 8,79 Hz); 6,86 (1H, d, J = 1,95 Hz); to 7.15 (2H, DM, J = 8,78 Hz); of 7.36 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 1705, 1615, 1595, 1580, 1510, 1460, 1370, 1290, 1160, 1135.

MS (m/z): 346 (M+,35CL), 317, 301, 274.

Getting 21. Ethyl (Z)-3-(4-chlorophenyl)-3-(3,4-acid)acrylate.

The compound was obtained as crystals (after paracrystalline.d: of 1.16 (3H, t, J = to 7.32 Hz); 3,81 (3H, s); 3,91 (3H, s); of 6.26 (1H, s); 6,70 (1H, d, J = 1,95 Hz); 6,79 (1H, DD, J = = 8,30 and 1.95 Hz); 7,12 - 7,40 (4H, m).

IR (l3) maxcm-1: 1710, 1600, 1590, 1515, 1490, 1460, 1255, 1170, 1135.

MS (m/z): 346 (M+,35CL), 317, 301, 274.

Getting 22. (E)-3-(4-chlorophenyl)-3-(3,4-acid)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 85% (so pl. 164-165aboutC).

NMR (CDCl3, 270 MHz) M. D.: 3,83 (38, s); the 3.89 (3H, s); of 6.29 (1H, s); 6,76 (1H, DD, J = 8.30 and of 1.95 Hz); to 6.80 (1H, d, J = 8,30 Hz); at 6.84 (1H, d, J = 1,95 Hz); to 7.15 (2H, DM, J = 8,30 Hz); to 7.35 (2H, DM, J = 8,30 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1610, 1595, 1515, 1465, 1260, 1175, 1135.

MS (m/z): 318 (M+); 303, 243.

23. (Z)-3-(4-chlorophenyl)-3-(3,4-acid)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 91% (so pl. 188-190aboutC).

NMR (CDCl3, 270 MHz) M. D.: of 3.80 (3H, s); to 3.92 (3H, s); 6,23 (1H, s); 6,72 (1H, d, J = 1,95 Hz); is 6.78 (1H, DD, J = 8.30 and of 1.95 Hz); 6,86 (1H, d, J = 8,30 Hz); 7.23 percent (2H, DM, J = 8,79 Hz); 7,31 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 2400-3600 (Shir.), 1690, 1605, 1585, 1515, 1490, 1465, 1415, 1255, 1135.

The compound was obtained as an oily substance with a yield of 13%.

NMR (CDCl3, 60 MHz) M. D.: a 1.11 (3H, t, J = 7 Hz); a 3.83 (3H, s); 3,88 (3H, s); 4,06 (2H, q, J = 7 Hz); 6,35 (1H, s); 's 6.75 to 7.00 (2H, m); 7,00 - to 7.50 (4H, m).

Getting 25. Ethyl (E)-3-(3-chlorophenyl)-3-(3,4-acid)acrylate.

The compound was obtained as an oily substance with a yield of 20%.

NMR (DCl3), 60 MHz) memorial plaques: to 1.15 (3H, t, J = 7 Hz); 3,81 (3H, s); are 3.90 (3H, s); 4,08 (2H, q, J = 7 Hz); of 6.29 (1H, s); 6,70 - to 7.00 (3H, m); 7,10 was 7.45 (4H, m).

Getting 26. (Z)-3-(3-chlorophenyl)-3-(3,4-acid)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 90% (so pl. 178-181aboutC).

NMR (CDCl3, 270 MHz) M. D.: a 3.83 (3H, s); the 3.89 (3H, s); 6,30 (1H, s); of 6.75 (1H, DD, J = 8.30 and of 1.95 Hz); to 6.80 (1H, d, J = 8,30); 6,85 (1H, d, J = 1,95 Hz); 7,10 (1H, dt, J = 7,81 and 1,46 Hz); then 7.20 (1H, t, J = 1,46 Hz); 7,31 (1H, t, J = 7,81 Hz); of 7.36 (1H, dt, J = 7,81 and 1,46 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1600, 1590, 1580, 1510, 1460, 1420, 1255, 1140.

MS (m/z): 318 (M+,35CL), 303.

Getting 27. (Z)-3-(3-Chlorophenyl)-3-(3,4-acid)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and GE is d, J = 1,95 Hz); is 6.78 (1H, DD, J = 8.30 and of 1.95 Hz); 6.87 in (1H, d, J = 8,30 Hz); 7,15 - 7,40 (4H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1600, 1580, 1565, 1515, 1460, 1420, 1255, 1135.

MS (m/z): 318 (M+,35CL), 303.

Getting 28. Ethyl (E)-3-(4-chlorophenyl)-3-(2,3-acid)acrylate.

The compound was obtained as crystals (recrystallization from hexane) to yield 4% (so pl. 82-84aboutC).

NMR (DCl3, 270 MHz) M. D.: of 1.17 (3H, t, J = to 7.32 Hz); 3,39 (3H, s); a-3.84 (3H, s); 4,10 (2H, q, J = to 7.32 Hz); 6,16 (1H, s); PC 6.82 (1H, DD, J = = 8.30 and 1,46 Hz); 6,93 (1H, DD, J = 8.30 and 1,46 Hz);? 7.04 baby mortality (1H, t, J = 8,30 Hz); 7,20 (2H, DM, J = 8,79 Hz); 7.29 trend (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 1715, 1620, 1600, 1580, 1475, 1430, 1370, 2260, 1170.

MS (m/z): 346 (M+,35CL), 315, 301, 287.

Receiving 29. Ethyl (Z)-3-(4-chlorophenyl)-3-(2,3-acid)acrylate.

The compound was obtained as crystals (recrystallization from hexane) to yield 37%, so pl. 90-92aboutC.

NMR (CDCl3, 270 MHz) M. D.: a 1.11 (3H, t, J = to 7.32 Hz); to 3.58 (3H, s); the 3.89 (3H, s); Android 4.04 (2H, q, J = to 7.32 Hz); to 6.43 (1H, s); 6,69 (1H, DD, J = 8.30 and of 1.47 Hz); 6,95 (1H, DD, J = 8.30 and of 1.47 Hz); was 7.08 (1H, t, J = 8,30 Hz); 7,28 (4H, s).

IR (l3)maxcm-1: 1720, 1626, 1590, 1580, 1480, 1430, 1370, 1260, 1170.

MS (m/z): 346 (M+,35
aboutC).

NMR (CDCl3, 270 MHz) M. D.: 3,39 (3H, s); a-3.84 (3H, s); 6,16 (1H, s); 6,79 (1H, DD, J = 8.30 and of 1.47 Hz); 6,93 (1H, DD, J = 8.30 and of 1.47 Hz);? 7.04 baby mortality (1H, T. J = 8,30 Hz); 7,20 (1H, DM, J = 8,79 Hz); 7,28 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1620, 1600, 1580, 1495, 1475, 1425, 1260.

MS (m/z): 318 (M+,35CL); 287.

Getting 31. (Z)-3-(4-chlorophenyl)-3-(2,3-acid)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 98%, so pl. 147aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 3.57 (3H, s); 3,88 (3H, s); 6,38 (1H, s); to 6.67 (1H, DD, J = 7,81 and 1,46 Hz); 6,94 (1H, DD, J = 7,81 and 1,46 Hz); 7,06 (1H, t, J = 7,81 Hz); 7,20 - 7,33 (4H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1620, 1590, 1580, 1495, 1480, 1425, 1265.

MS (m/z): 318 (M+,35CL), 287.

Getting 32. Ethyl(Z)-3-(4-chlorophenyl)-3-(4-isobutoxide)acrylate.

The compound was obtained as an oily substance with a yield of 13%.

NMR (DCl3, 270 MHz) M. D.: 1,02 (6N, d, 1 = 6,83 Hz); 1.14 in (3H, t, J = to 7.32 Hz); 2,00 - to 2.15 (1H, m); and 3.72 (2H, d, J = 6,35 Hz); of 4.05 (2H, q, J = to 7.32 Hz); 6,30 (1H, s); 6,83 (2H, DM, J = =8,79 Hz); 7,14 (2H, DM, J = 8,79 Hz); then 7.20 (2H, DM, J = 8,79 Hz); to 7.35 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1

The compound was obtained as an oily substance with a yield of 16%.

NMR (DCl3, 270 MHz) M. D.: 1,03 (6N, d, J = 6,83 Hz); of 1.17 (3H, t, J = to 7.32 Hz); 2,00 - of 2.20 (1H, m), 3,74 (2H, d, J = 6,35 Hz); 4.09 to (2H, q, J = to 7.32 Hz); 6,23 (1H, s); 6.89 in (2H, DM, J = 9.28 are Hz); 7,11 (2H, DM, J = 9.28 are Hz); 7,22 (2H, DM, J = 8,79 Hz); 7.29 trend (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 1710, 1605, 1590, 1510, 1490, 1470, 1370, 1285, 1160.

MS (m/z): 368 (M+), 35CL), 313, 302.

Getting 34. (Z)-3-(4-chlorophenyl)-3-(4-isobutoxide)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 80%, so pl. 172-174aboutC.

NMR (DCl3, 270 MHz) M. D.: 1,02 (6N, d, J = 6,83 Hz); 1,95 - of 2.20 (1H, m); and 3.72 (2H, d, J = 6,84 Hz); 6,27 (1H, s); 6,83 (2H, DM, J = 8,30 Hz); 7,13 (2H, DM, J = 8,30 Hz); 7.18 in (2H, DM, J = 8,79 Hz); 7,34 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1600, 1590, 1510, 1295, 1250, 1175.

MS (m/z): 330 (M+,35Cl), 274, 257.

Receive 35. (E)-3-(4-chlorophenyl)-3-(4-isobutoxide)acrylic acid.

The compound obtained in the form of crystals after recrystallization from a mixture of methylene chloride and hexane) to yield 100%, so pl. 150-152aboutC.

NMR (CDCl3, 270 MHz) M. D.: 1,04 (6N, d, J = 6,35 Hz); 2,00-ptx2">

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1610, 1590, 1515, 1290, 1245, 1175.

MS (m/z): 330 (M+,35CL), 274, 257.

Getting 36. Ethyl(Z)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 19%.

NMR (CDCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = to 7.32 Hz); 1.14 in (3H, t, J = 7,33 Hz); 1,74 - 1,90 (2H, m); to 3.92 (2H, t, J = 6,83 Hz); of 4.05 (2H, q, J = 7,33 Hz); of 6.31 (1H, s); 6,83 (2H, DM, J = 9.28 are Hz); 7,14 (1H, DM, J = 8,79 Hz); then 7.20 (2H, DM, J = 9.28 are Hz); of 7.36 (2H, DM, J = 8,79).

IR (l3)maxcm-1: 1705, 1600, 1595, 1510, 1370, 1275, 1250, 1160, 1150.

MS (m/z): 344 (M+,35CL), 302, 299, 272, 257, 230.

Getting 37. Ethyl (E)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 27%.

NMR (DCl3, 270 MHz) M. D.: of 1.05 (3H, t, J = 7,33 Hz); of 1.16 (3H, t, J = 7,33 Hz); 1,75 - of 1.95 (2H, m); of 3.95 (2H, t, J = 6,84 Hz); 4.09 to (2H, q, J = 7,33 Hz); 6,23 (1H, s); 6.89 in (2H, DM, J = 8,78 Hz); for 7.12 (2H, DM, J = 8,78 Hz); 7,22 (2H, DM, J = 8,79 Hz); 7.29 trend (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 1710, 1610, 1510, 1490, 1370, 1290, 1240, 1170, 1150.

MS (m/z): 344 (M+, 35CL), 302, 299, 272, 257, 230.

Getting 38. (Z)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)acrylic acid.

Connection received in CLASS="ptx2">

NMR (CDCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = to 7.32 Hz); 1,70 - 1,90 (2H, m); 3,93 (2H, t, J = 6,84 Hz); 6,27 (1H, s); 6,83 (2H, DM, J = 8,79 Hz); 7,14 (2H, DM, J = 8,30 Hz); 7,19 (2H, DM, J = 8,69 Hz); 7,34 (2H, DM, J = 8,30).

IR (l3maxcm-1: 2400 - 3600 (Shir.), 1695, 1600, 1595, 1510, 1280, 1255, 1180.

MS (m/z): 316 (M+,35CL), 274, 257, 229.

Getting 39. (E)-3-(4-chlorophenyl)-3-(4-propoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 97%, so pl. 145-147aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 1.06 (3H, t, J = 7,33 Hz); 1,75 - 1,90 (2H, m); of 3.95 (3H, t, J = 6,35 Hz); to 6.19 (1H, m); to 6.88 (2H, DM, J = 8,79 Hz); 7,13 (2H, DM, J = 8,79 Hz); 7,21 (2H, DM, J = 8,79 Hz); 7,30 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1610, 1590, 1510, 1495, 1290, 1270, 1250, 1175.

MS (m/z): 316 (M+,35CL), 274, 257, 229.

Getting 40. Ethyl (E)-3-(4-forfinal)-3-(3,4,5-trimethoxyphenyl)acrylate.

The compound was obtained as crystals after recrystallization from diethyl ether) to yield 22%, so pl. 133-135aboutC.

NMR (CDCl3, 270 MHz) memorial plaques: to 1.15 (3H, t, J = to 7.32 Hz); 3,78 (6N, C); a 3.87 (3H, s); 4,07 (2H, q, J = to 7.32 Hz); of 6.31 (1H, s); 6,48 (2H, s); 7.03 is - 7,13 (2H, m); 7,17 - of 7.25 (2H, m).

IR (l3)max- (Z)-3-(4-forfinal)-3-(3,4,5-trimethoxyphenyl)acrylate.

The compound was obtained as crystals (after recrystallization from a mixture of diethyl ether and hexane) to yield 37%, so pl. 62-64aboutC.

NMR (CDCl3, 270 MHz) memorial plaques: to 1.14 (3H, t, J = 7,33 Hz); 3,80 (6N, C); are 3.90 (3H, s); 4,08 (2H, q, J = 7,33 Hz); of 6.26 (1H, s); 6,41 (2H, s); 6,98 - was 7.08 (2H, m); 7,27 was 7.36 (2H, m);

IR (l3) maxcm-1: 1710, 1600, 1585, 1505, 1465, 1415, 1370, 1310, 1160, 1130.

MS (m/z): 360 (M+), 345, 315.

Getting 42. (E)-3-(4-forfinal)-3-(3,4,5-trimethoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride, diethyl ether and hexane) to yield 98%, so pl. 201-204aboutC.

NMR (DCl3, 270 MHz) M. D.: 3,78 (6N, C); a 3.87 (3H, s); 6,28 (1H, s); 6,46 (2H, s); 7,02 for 7.12 (2H, m); 7,12 - of 7.25 (2H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1600, 1580, 1505, 1130.

MS (m/z): 332 (M+), 317.

Getting 43. (Z)-3-(4-forfinal)-3- (3,4,5-trimethoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 100%, so pl. 187-189aboutC.

NMR (CDCl3, 270 MHz) M. D.: 3,79 (6N, C); 3,91 (3H, s); 6,24 (1H, s); 6.42 per (2H, s); 6,99 - to 7.09 (2H, m); 7,27 - to 7.35 (2H, m).

IR (l3)maetel (E)-3-(3,4-acid)-3-(4-methoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 20%.

NMR (CDCl3, 270 MHz) M. D.: of 1.16 (3H, t, J = to 7.32 Hz); a 3.83 (3H, s); of 3.85 (3H, s); the 3.89 (3H, s); 4,08 (2H, q, J = to 7.32 Hz); 6,23 (1H, s); 6,77 - 6,89 (3H, m); 6,91 (2H, DM, J = 8,78 Hz); 7,16 (2H, DM, J = 8,78 Hz).

IR (l3)maxcm-1: 1705, 1605, 1580, 1510, 1465, 1290, 1165, 1135.

MS (m/z): 342 (M+), 313, 297.

45. Ethyl (Z)-3-(3,4-acid)-3-(4-methoxyphenyl)acrylate.

The compound was obtained as an oily material with 30% yield.

NMR (CDCl3, 270 MHz) memorial plaques: to 1.15 (3H, t, J = to 7.32 Hz); 3,81 (3H, s); of 3.85 (3H, s); to 3.92 (3H, s); 4,07 (2H, q, J = to 7.32 Hz); 6,24 (1H, s); of 6.71 (1H, d, J = 1,95 Hz); 6,77 - 6,94 (4H, m); 7,26 (2H, DM, J = 8,79 Hz).

IR (l3)maxcm-1: 1705, 1600, 1510, 1465, 1250, 1170, 1135.

MS (m/z): 342 (M+), 313, 297.

Getting 46. (E)-3-(3,4-acid)-3- (4-methoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 91%, so pl. 161-163aboutC.

NMR (CDCl3, 270 MHz) M. D.: is 3.82 (3H, s); of 3.85 (3H, s); the 3.89 (3H, s); of 6.20 (1H, s); 6,74 - PC 6.82 (2H, m); 6,74 (1H, Shir.C); 6,89 (2H, DM, J = 8,79 Hz); 7,17 (2H, DM, J = 8,79 Hz).

IR (l3) maxcm-1: 2400 - 3600 (Shir.), 1685, 1605, 1595, 1510, 1465, 1290, 1�relova acid.

The compound was obtained as crystals after recrystallization from methylene chloride and hexane) to yield 97%, so pl. 149-152aboutC.

NMR (DCl3, 270 MHz) M. D.: 3,81 (3H, s); a 3.83 (3H, s); to 3.92 (3H, s); 6,21 (1H, s); 6,74 (1H, d, J = 1,95 Hz); to 6.80 (1H, DD, J = 8.30 and of 1.95 Hz); 6,82 - 6,83 (3H, m); 7,14 - 7,29 (2H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1600, 1515, 1465, 1255, 1175, 1135.

MS (m/z): 314 (M+), 229, 270.

Receive 48. Ethyl (Z)-3-(3,4-dichloromethyl)-3-4-methoxyphenyl)acrylate.

The connection was received in the form of an oily liquid, yield 62%.

NMR (CDCl3, 60 MHz) memorial plaques: to 1.15 (3H, t, J = 7 Hz); of 3.80 (3H, s); 4,06 (2H, q, J = 7 Hz); 6,35 (1H, s); 6,8 - 7,4 (7H, m).

Getting 49. Ethyl (E)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acrylate.

The connection was received in the form of an oily liquid, yield 23%.

NMR (CDCl3, 60 MHz) M. D.: of 1.16 (3H, t, J = 7 Hz); of 3.84 (3H, s); 4,06 (2H, q, J = Hz); 6,23 (1H, s); 6,7 - 7,5 (7H, m).

Getting 50. (Z)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 84%, so pl. 181-184aboutC.

NMR (CD3OD, 270 MHz) M. D.: of 3.80 (3H, s); 6,36 (1H, s); 6,91 (2H, DM, J = 9.28 are Hz); was 7.08 (1H, DD, J = 8.30 and of 1.95 Hz); 7.23 percent (2H, the 5, 1510, 1288, 1254, 1214, 1178, 1162.

MS (m/z): 322 (M+,35CL), 305, 277.

Getting 51. (E)-3-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 95%, so pl. 193-196aboutC.

NMR (CD3OD, 270 MHz) M. D.: 3,83 (38, s); 6,30 (1H, IP); 6,93 (2H, DM, J = 8,79 Hz); for 7.12 (2H, DM, J = 8,79 Hz); 7.23 percent (1H, DD, J = 8.30 and of 1.95 Hz); 7,38 (1H, d, J = 1,95 Hz); 7,50 (1H, d, J = 8,30 Hz).

IR (KBR)maxcm-1: 2300 - 3400 (Shir.), 1688, 1662, 1602, 1512, 1407, 1281, 1253, 1207, 1177.

MS (m/z): 322 (M+,35CL); 305, 277.

Getting 52. Ethyl (E)-3-(3,4-acid)-3-(3-triptoreline)acre-lat.

The compound was obtained as crystals (recrystallization from hexane) to yield 13%, so pl. 72-74aboutC.

NMR (CDCl3, 270 MHz) M. D.: a 1.08 (3H, t, J = to 7.32 Hz); of 3.84 (3H, s); the 3.89 (3H, s); a 4.03 (2H, q, J = to 7.32 Hz); 6,37 (1H, s); 6,72 (1H, DD, J = = 8,30 and 1.96 Hz); to 6.80 (1H, pH, J = 8,30 Hz); 6.87 in (1H, d, J = 1,96 Hz); 7,35 - of 7.70 (4H, m).

IR (l3)maxcm-1: 1710, 1585, 1515, 1460, 1370.

MS (m/z): 380 (M+), 361, 335.

Getting 53. Ethyl (Z)-3-(3,4-acid)-3- (3-triptoreline)acrylate.

The compound was obtained as an oily substance from the output is N, d, J = = 1,95 Hz); for 6.81 (1H, DD, J = 8.30 and a 1.96 Hz); 6.89 in (1H, d, J = 8,30 Hz); 7,40 is 7.50 (2H, m); EUR 7.57 - to 7.68 (2H, m).

IR (l3)maxcm-1: 1710, 1600, 1580, 1515, 1460, 1370, 1325.

MS (m/z): 380 (M+), 361, 335.

Getting 54. (E)-3-(3,4-acid)-3- (3-triptoreline)acrylic acid.

The compound was obtained as crystals (after paracrystalline a mixture of methylene chloride and hexane) to yield 100%, so pl. 142-144aboutC.

Getting 55. (Z)-3-(3,4-acid)-3- (3-triptoreline)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 100%, so pl. 140-143aboutC.

Getting 56. Ethyl (E)-3-(3,4-acid)-3-(4-were)acrylate.

The compound was obtained as crystals (recrystallization from hexane) to yield 21%, so pl. 75-77aboutC.

NMR (DCl3, 270 MHz) memorial plaques: to 1.14 (3H, t, J = 7,32); 3,39 (3H, sing.); a 3.83 (3H, s); 3,88 (3H, s); 4,06 (2H, square, J = to 7.32 Hz); 6,27 (1H, s); 6,77 (1H, d, J = 8,30 Hz); for 6.81 (1H, DD, J = 8.30 and of 1.95 Hz); 6.89 in (1H, d, J = 1,95 Hz); 7,01 - 7,22 (4H, m).

IR (l3)maxcm-1: 1705, 1600, 1580, 1510, 1465, 1440, 1370, 1290, 1250, 1160, 1130.

MS (m/z): 326 (M+), 297, 281, 254.

Getting 57. Ethyl (Z)-3-(3,4-dimethoxy Aksana with 38%, so pl. 69-70aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 1.16 (3H, t, J = to 7.32 Hz); a 2.36 (3H, s); 3,81 (3H, s); 3,91 (3H, s); 4,08 (2H, q, J = to 7.32 Hz); 6,27 (1H, s); 6,72 (1H, d, J = 1,95 Hz); for 6.81 (1H, DD, J = 7,81 and 1.95 Hz); to 6.88 (1H, d, J = 7,81 Hz); 7,13 (2H, DM, J = of 9.30 Hz); 7,21 (2H, DM, J = 8,30).

IR (l3)maxcm-1: 1710, 1600, 1580, 1510, 1465, 1415, 1370, 1250, 1160, 1135.

MS(m/z): 326 (M+), 297, 281, 254.

Getting 58. (E)-3-(3,4-acid)-3-(4-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 97%, so pl. 167-170aboutC.

NMR (CDCl3, 270 MHz) M. D.: 2,39 (3H, s); 3,88 (3H, s); to 3.92 (3H, s); 6,24 (1H, s); 7,79 (1H, m); 6,86 (1H, Shir. C.); 7,08 - 7,22 (4H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1600, 1580, 1510, 1465, 1440, 1420, 1325, 1290, 1250, 1175, 1135.

MS (m/z): 298 (M+), 283.

Getting 59. (Z)-3-(3,4-acid)-3-(4-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 96%, so pl. 185-188aboutC.

NMR (CDCl3, 270 MHz) M. D.: a 2.36 (3H, s); of 3.80 (3H, s); to 3.92 (3H, s); 6,24 (1H, s); of 6.75 (1H, d, J = 1,95 Hz); 6,79 (1H, DD, J = 8.30 and of 1.95 Hz); 6,86 (1H, d, J = 8,30 Hz); 7,10 - of 7.23 (4H, m).

IR (l3 Getting 60. Ethyl (Z)-3-(3,4-dichlorophenyl)-3-(3-were)acrylate.

The compound was obtained as an oily substance with a yield of 52%.

NMR (CDCl3, 270 MHz) M. D.: of 1.17 (3H, t, J = to 7.32 Hz); of 2.33 (3H, s); 4,08 (2H, q, J = to 7.32 Hz); 6,36 (1H, s); 7.03 is - 7,13 (3H, m); 7,15 - of 7.23 (2H, m), 7,30 (1H, d, J = 1,95 Hz); 7,46 (1H, d, J = 8,30 Hz).

IR (Cl3)maxcm-1: 1715, 1620, 1470, 1370, 1280, 1170, 1150.

MS (m/z): 334 (M+,35CL), 305, 289, 262.

Getting 61. Ethyl (E)-3-(3,4-dichlorophenyl)-3-(3-were)acrylate.

The compound was obtained as an oily substance with a yield of 19%.

NMR (CDCl3, 270 MHz) M. D.: a 1.11 (3H, t, J = to 7.32 Hz); 2,35 (3H, s); of 4.05 (2H, q, J = to 7.32 Hz); 6,30 (1H, s); 6,95 - 7,05 (2H, m); for 7.12 (1H, DD, J = 8,79 and 1.95 Hz); 7,15 - to 7.32 (2H, m). 7,379 (1H, d, J = 1,95 Hz); 7,385 (1H, d, J = 8,79 Hz).

IR (l3)maxcm-1: 1720, 1620, 1470, 1380, 1370, 1350, 1280, 1250, 1175.

MS (m/z): 334 (M+,35CL), 305, 289, 262.

Getting 62. (Z)-3-(3,4-dichlorophenyl)-3-(3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 95%, so pl. 163-165aboutC.

NMR (DCl3, 270 MHz) M. D.: of 2.33 (3H, s); 6,33 (1H, s); 7,00 - 7,10 (3H, m); 7.18 in - 7,28 (2H, m), 7,29 (1H, d, J = 1,95 Hz); was 7.45 (1H, d, J = = 7,81 Hz).

IR (lCLASS="ptx2">

Getting 63. (E)-3-(3,4-dichlorophenyl)-3-(3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 92%, so pl. 152-154aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 2.34 (3H, s); of 6.26 (1H, s); 6,94 - 7,03 (2H, m); to 7.09 (1H, DD, J = 8.30 and of 1.95 Hz); 7.18 in (1H, d, J = 1,96 Hz); to 7.35 (1H, d, J = 1,95 Hz); 7,39 (1H, d, J = 8,30 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1620, 1470, 1410, 1285, 1180, 1130.

MS (m/z): 306 (M+,35CL), 291, 261.

Getting 64. Ethyl (E)-3-(3,4-acid)-3-(3-were)acrylate.

The compound was obtained as an oily substance with a yield of 23%.

NMR (CDCl3, 270 MHz) M. D.: a 1.11 (3H, t, J = to 7.32 Hz); a 2.36 (3H, m); a 3.83 (3H, s); 3,88 (3H, s); Android 4.04 (2H, q, J = to 7.32 Hz); of 6.29 (1H, s); 6.75 in - 6,84 (2H, m); 6.90 to (1H, Shir. C); 6,94 - 7,05 (2H, m); 7,15 - 7,31 (2H, m).

IR (l3)maxcm-1: 1710, 1600, 1580, 1515, 1470, 1445, 1330, 1295, 1255, 1160, 1145, 1139.

MS (m/z): 326 (M+), 297, 281, 254.

Receive 65. Ethyl (Z)-3-(3,4-acid)-3-(3-were)acrylate.

The compound was obtained as an oily substance with a yield of 33%.

NMR (CDCl3, 270 MHz) M. D.: of 1.16 (3H, t, J = 7,33 Hz); of 2.33 (3H, s); 3,81 (3H, s); to 3.92 (3H, s); 4,08 (2H, q, J = to 7.32 Hz); 6,72 (1H, d, J = = a 1.96 Hz); for 6.81 (1H, is 1470, 1260, 1180, 1160, 1145, 1135.

MS (m/z): 326 (M+), 297, 281, 254.

Getting 66. (E)-3-(3,4-acid)-3-(3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of diethyl ether and hexane) to yield 95%, so pl. 140-143aboutC.

NMR (CDCl3, 270 MHz) M. D.: 2,35 (3H, s); 3,82 (3H, s); the 3.89 (3H, s); 6,27 (1H, s); 6,74 - 6,83 (2H, m); 6.87 in (1H, Shir. C); 6,99 - 7,06 (2H, m); 7,15 - 7,31 (2H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1600, 1580, 1515, 1470, 1260, 1170, 1145, 1130.

MS (m/z): 298 (M+), 283, 253.

Getting 67. (Z)-3-(3,4-acid)-3-(3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 96%, so pl. 148-150aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 2.33 (3H, s); 3,81 (3H, s); to 3.92 (3H, s); 6,24 (2H, s); of 6.75 (1H, d, J = 1,96 Hz); to 6.80 (1H, DD, J = 8.30 and a 1.96 Hz); 6.87 in (1H, d, J = 8,30 Hz); 7,05 - 7,14 (2H, m); 7,16 - 7,24 (2H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1605, 1585, 1515, 1450, 1440, 1420, 1255, 1175, 1135.

MS (m/z): 298 (M+), 283, 253.

Getting 68. Ethyl (Z)-3-(2-chlorophenyl)-3-(4-methoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 81%.

IR (l3)maxcm-1: 1710, 1605, 1590, 1575, 1515, 1465, 1370, 1355, 1280, 1255, 1160.

MS (m/z): 316 (M+,35CL), 281, 271, 253.

Getting 69. (Z)-3-(2-chlorophenyl)-3-(4-methoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 85%, so pl. 162-164aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 3.80 (3H, s); 6,44 (1H, s); 6,84 (2H, DM, J = 8,79 Hz); 7,09 - 7,16 (1H, m); from 7.24 (2H, DM, J = 8,79 Hz); 7,26 - to 7.35 (2H, m); 7,37 - 7,46 (1H, m).

IR (l3) maxcm-1: 2400 - 3600 (Shir.), 1700, 1620, 1605, 1595, 1575, 1515, 1425, 1290, 1260, 1180, 1160.

MS (m/z): 288 (M+,35CL), 253, 238.

Receive 70. Ethyl (Z)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 8%.

NMR (CDCl3, 270 MHz) M. D.: of 1.13 (3H, t, J = to 7.32 Hz); of 3.78 (3H, s); 4,06 (2H, q, J = to 7.32 Hz); 6,37 (1H, s); for 6.81 (1H, t, J = 1,96 Hz); 6,86 (1H, DDD, J = 8,31, and 0.98 to 1.96 Hz); 6,91 (1H, DDD, J = 8,31, and 0.98 to 1.96 Hz); 7,10 (1H, dt, J = =7,81 and 1.95 Hz); then 7.20 (1H, t, J = 1,95 Hz); of 7.25 (1H, t, J = 7,81 Hz); 7,31 (1H, t, J = 7,81 Hz); to 7.35 (1H, dt, J = 7,81 and 1.95 Hz).

IR (l3) maxcm-1: 1715, 1620, 1600, 1580, 1490, 1470, 1435, 1370, 1350, 1290, 1280, 1170.

MS (m/z): 316 M+,

NMR (DCl3, 270 MHz) M. D.: of 1.12 (3H, t, J = to 7.32 Hz); with 3.79 (3H, s); 4,06 (2H, q, J = to 7.32 Hz); 6,33 (1H, s); 6,72 (1H, DD, J = 2.44 and 1,46 Hz); 6,79 (1H, dt, J = 7,81 and 1,46 Hz); 6,93 (1H, DDD, J = 8,30, 2.44 and 1,46 Hz); 7.18 in (1H, dt, J = =7,32 and 1,46 Hz); 7,22 and 7.36 (4H, m).

IR (l3)maxcm-1: 1720, 1620, 1590, 1580, 1570, 1490, 1470, 1430, 1370, 1350, 1290, 1260, 1170.

MS (m/z): 316 (M+,35CL), 287, 271, 243, 228.

Getting 72. (Z)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 98%, so pl. 115-117aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 3.78 (3H, s); 6,35 (1H, s); is 6.78 (1H, t, J = 1,47 Hz); at 6.84 (1H, DM, J = 7,81 Hz); of 7.25 (1H, t, J = 7,81 Hz); 7,30 (1H, t, J = to 7.32 Hz); of 7.36 (1H, dt, J = 7,33 and 1.47 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1620, 1600, 1580, 1490, 1435, 1410, 1345, 1290, 1150.

MS (m/z): 188 (M+,35CL), 271, 243.

Getting 73. (E)-3-(3-chlorophenyl)-3-(3-methoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 96%, so pl. 140-142aboutC.

NMR (CDCl3, 270 MHz) M. D.: with 3.79 (3H, s); 6,30 (1H, s); 6,72 (1H, DD, J = 2.44 and of 1.47 Hz); is 6.78 (1H, DM, J = to 7.32 Hz); 6,93 (1H, DDD, J = 8,30, 2,44 and 0.97 Hz); 7,16 (1H, dt, J = 1430, 1350, 1285.

MS (m/z): 188 (M+,35CL), 271, 243.

Getting 74. Ethyl (Z)-3-(3-chlorophenyl-3-(4-methoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 10%.

NMR (CDCl3, 270 MHz) M. D.: 1,12 (2H, t, J = to 7.32 Hz); 3,82 (3H, s); of 4.05 (2H, q, J = to 7.32 Hz); 6,32 (1H, s); 6,85 (2H, DM, J = 9.28 are Hz); to 7.09 (1H, DM, J = 7,30 and 1.96 Hz); 7.18 in - 7,39 (5H, m).

IR (l3) maxcm-1: 1710, 1605, 1600, 1570, 1515, 1465, 1420, 1370, 1350, 1290, 1275, 1255, 1170, 1155.

MS (m/z): 315 (M+,35CL), 287, 271, 144, 228.

Obtaining 75. Ethyl (E)-3-(3-chlorophenyl)-3-(4-methoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 14%.

NMR (CDCl3, 270 MHz) M. D.: of 1.17 (3H, t, J = to 7.32 Hz); of 3.84 (3H, s); 4.09 to (2H, q, J = to 7.32 Hz); and 6.25 (1H, s); 6,91 (2H, DM, J = 8,79 Hz); to 7.15 (2H, DM, J = 8,79 Hz); 7,15 and 7.36 (4H, m).

IR (l3)maxcm-1: 1715, 1610, 1570, 1515, 1470, 1370, 1355, 1295, 1250, 1175.

MS (m/z):316 (M+,35CL), 287, 271, 244, 228.

Getting 76. (Z)-3-(3-chlorophenyl)-3-(4-methoxyphenyl)acrylic acid.

The compound was obtained as crystals after recrystallization from a mixture of methylene chloride and hexane to yield 94%, so pl. 158-160aboutC.

NMR (CDCl3, 270 MHz) M. D.: is 3.82 (3H, s); of 6.29 (1H, s); 6,85 (2H, DM, J = 9,281590, 1570, 1515, 1425, 1285, 1255, 1180.

MS (m/z): 288 (M+,35CL), 271, 243.

Getting 77. (E)-3-(3-chlorophenyl)-3-(4-methoxyphenyl)acrylic acid.

The compound was obtained as crystals after recrystallization from a mixture of methylene chloride and hexane to yield 92%, so pl. 119-120aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 3.85 (3H, s); 6,21 (1H, s); make 6.90 (2H, DM, J = 8,79 Hz); to 7.15 (2H, DM, J = 8,79 Hz); 7,12 - 7,38 (4H, m).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1610, 1570, 1515, 1420, 1295, 1250, 1180.

MS (m/z): 288 (M+,35CL), 271; 243.

Getting 78. Ethyl (Z)-3-(3,4-dichlorophenyl)-3-(4-propoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 4%.

NMR (DCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = to 7.32 Hz); of 1.16 (3H, t, J = to 7.32 Hz), 1,70 - 1,90 (2H, m); 3,93 (2H, t, J = 6,84 Hz); 4,07 (2H, q, J = to 7.32 Hz); 6,32 (1H, s); 6,84 (2H, DM, J = 8,79 Hz); 7,06 (1H, DD, J = 8.30 and of 1.95 Hz); then 7.20 (2H, DM, J = 8,79 Hz); 7.29 trend (1H, d, J = 1,95 Hz); was 7.45 (1H, d, J = 8,30 Hz).

MS (m/z): 378 (M+,35CL), 336, 333, 308, 305, 291, 264.

Getting 79. Ethyl (E)-3-(3,4-dichlorophenyl)-3-(4-propoxyphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 5%.

NMR (CDCl3, 270 MHz) M. D.: of 1.05 (3H, t, J = to 7.32 Hz); of 1.17 (3H, t, J = 7, 32 Hz); 1,75 - 1,90 (2H, m); of 3.95 (2H, t, J = 7,39 (1H, d, J = 8,30 Hz).

IR (l3)maxcm-1: 1715, 1630, 1515, 1470, 1390, 1370, 1350, 1290, 1280, 1245, 1170.

MS (M+,35CL), 336, 333, 308, 305, 291, 264.

80. (Z)-3-(3,4-dichlorophenyl)-3-(4-propoxyphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 96%, so pl. 161-163aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = to 7.32 Hz); 1,70 - 1,90 (2H, m); 3,93 (2H, t, J = 6,84 Hz); of 6.29 (1H, s); 6,85 (2H, DM, J = 8,79 Hz); 7,06 (1H, DD, J = 8.30 and of 1.95 Hz); 7,19 (2H, DM, J = 8,79 Hz); 7,28 (1H, d, J = 1,95 Hz); was 7.45 (1H, d, J = 8,30 Hz).

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1605, 1590, 1555, 1475, 1285, 1255, 1180.

MS (m/z): 350 (M+,35CL), 308, 291, 263.

Getting 81. (E)-3-(3,4-dichlorophenyl)-3-(4-propoxyphenyl)acrylic acid,

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 85%, so pl. 155-157aboutC.

Getting 82. Ethyl (E)-3-(4-ethoxy-3-methoxyphenyl)cinnamate.

The compound was obtained as crystals (recrystallization from hexane) to yield 21%, so pl. 89-91aboutC.

NMR (CDCl3, 270 MHz) M. D.: 1,10 (3H, t, J = to 7.32 Hz); of 1.46 (3H, t, J = 7,33 Hz); 3,81 (3H, s); a 4.03 (2H, q, J = 7,33 GW>max
cm-1: 1710, 1615, 1600, 1580, 1515, 1480, 1470, 1370, 1320, 1290, 1250, 1160, 1135.

MS (m/z): 326 (M+), 297, 281, 253, 226.

Getting 83. Ethyl (Z)-3-(4-ethoxy-3-methoxyphenyl)cinnamate.

The compound was obtained as an oily substance with a yield of 21%.

NMR (CDCl3, 270 MHz) memorial plaques: to 1.15 (3H, t, J = to 7.32 Hz); for 1.49 (3H, t, J = to 7.32 Hz); of 3.80 (3H, s); 4,08 (2H, q, J = to 7.32 Hz); to 4.14 (2H, q, J = = to 7.32 Hz); 6,28 (1H, s); of 6.73 (1H, d, J = 1,95 Hz); 6,79 (1H, DD, J = 8.30 and of 1.95 Hz); 6.87 in (1H, d, J = 8,30 Hz); 7,29 - 7,40 (5H, m).

IR (l3)maxcm-1: 1710, 1605, 1580, 1515, 1480, 1470, 1450, 1410, 1370, 1355, 1320, 1250, 1160, 1130.

MS (m/z): 326 (M+), 297, 281, 253, 226.

Getting 84. (E)-3-(4-ethoxy-3-methoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of tetrahydrofuran and hexane) to yield 93%, so pl. 200-202aboutC.

NMR (mixture 1:1 by volume DCl3and CD3OD, 270 MHz) M. D.: a 1.45 (3H, t, J = of 6.96 Hz); of 3.80 (3H, s); of 4.11 (2H, q, J = of 6.96 Hz); 6,32 (1H, s); to 6.80 (1H, DD, J = 8,43 and 1.83 Hz); at 6.84 (1H, d, J = 8,43 Hz); 6,88, 7,18 - 7,27 (2H, m); 7,32 - 7,42 (3H, m).

IR (KBR)maxcm-1: 2400 - 3600 (Shir.), 1692, 1660, 1605, 1587, 1514, 1479, 1421, 1402, 1324, 1297, 1274, 1255, 1204, 1137.

MS (m/z): 298 (M+), 270, 253, 225.

Getting 85. (Z)-3-(4-ethoxy-3-methoxyphenyl)cinnamic acid.

NMR (CDCl3, 270 MHz) memorial plaques: for 1.49 (3H, t, J = 7,33 Hz); of 3.80 (3H, s); to 4.14 (2H, q, J = to 7.32 Hz); and 6.25 (1H, s); 6,72 - 6,86 (3H, m); 7,27 - the 7.43 (5H, m).

IR (l3)maxcm-1: 2400-3600 (Shir.), 1690, 1605, 1580, 1515, 1470, 1450, 1415, 1255, 1135.

MS (m/z): 298 (M+), 270, 253, 225.

Getting 86. Ethyl (E)-3-(4-butoxy-3-methoxyphenyl)cinnamate.

The compound was obtained as an oily substance with a yield of 21%.

NMR (CDCl3, 270 MHz) M. D.: 1,43 - and 1.54 (2H, m); 1,78 is 1.86 (2H, m); of 3.80 (3H, s); was 4.02 (2H, t, J = 6,84 Hz); a 4.03 (2H, q, J = 7,33 Hz); of 6.31 (1H, s); 6,77 (2H, Shir. C); 6,79 (2H, Shir.C); 7,17 - 7,24 (2H, m); 7,34 - 7,41 (3H, m).

IR (Cl3)maxcm-1: 1710, 1690, 1610, 1595, 1580, 1510, 1465, 1370, 1290, 1270, 1250, 1160, 1135.

MS (m/z): 354 (M+), 309, 298, 269, 253, 226.

Getting 87. Ethyl (Z)-3-(4-butoxy-3-methoxyphenyl)cinnamate.

The compound was obtained as an oily substance with a yield of 47%.

NMR (CDCl3, 60 MHz) M. D.: and 0.98 (3H, t, J = 7 Hz); of 1.13 (3H, t, J = 7 Hz); 1.30 and of 2.20 (4H, m); of 3.78 (3H, s); was 4.02 (2H, t, J = 7 Hz); 4,10 (2H, q, J = 7 Hz); 6,30 (1H, s); 6,70 - 7,05 (3H, m).

Getting 88. (E)-3-(4-butoxy-3-methoxyphenyl)cinnamate.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 92%, so pl. 140-143about

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1690, 1610, 1595, 1580, 1510, 1500, 1470, 1420, 1320, 1250, 1135.

MS (m/z): 325 (M+), 270, 253, 237.

Getting 89. Ethyl (Z)-3-(3,4-dichlorophenyl)-3-(4-ethylphenyl)acrylate.

The compound was obtained as an oily substance with a yield of 50%.

NMR (CDCl3, 270 MHz) M. D.: of 1.16 (3H, t, J = to 7.32 Hz); of 1.24 (3H, t, J = to 7.32 Hz); of 2.66 (2H, q, J = to 7.32 Hz); 4,08 (2H, q, J = to 7.32 Hz); 6,37 (1H, s); 7,06 (1H, DD, J = 8.30 and of 1.95 Hz); 7,12 - 7,24 (4H, m), 7,30 (1H, d, J = 1,95 Hz); 7,46 (1H, d, J = 8,30 Hz).

IR (l3)maxcm-1: 1710, 1620, 1610, 1470, 1370, 1275,1170, 1160.

MS (m/z): 347 (M+,35CL), 319, 303, 276.

Getting to 90. Ethyl (E)-3-(3,4-dichlorophenyl)-3-(4-ethylphenyl)acrylate.

The compound obtained in the form of an oily substance with a yield of 14%.

NMR (CDCl3, 60 MHz) M. D.: 1,10 (3H, t, J = 7 Hz); of 1.27 (3H, t, J = 7 Hz); 2,70 (2H, q, J = 7 Hz); of 4.05 (2H, t, J = 7 Hz); 6,27 (1H, s); 6,98 - of 7.60 (7H, m).

Getting 91. (Z)-3-(3,4-dichlorophenyl)-3-(4-ethylphenyl)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 94%, so pl. 172-174aboutC.

NMR (CDCl3, 270 MHz) = Of 7.82 Hz).

IR (Cl3)maxcm-1: 2400 - 3600 (Shir.) 1690, 1620, 1605, 1470, 1280, 1180, 1160, 1120.

MS (m/z): 320 (M+, 35CL), 305, 291, 275.

Getting 92. Ethyl (Z)-3-(4-propoxyphenyl)cinnamate. Oily substance (35%).

NMR (CDCl3, 270 MHz) M. D.: of 1.05 (3H, t, J = 7,33 Hz); 1,67 (3H, t, J = 7,33 Hz); 1,75 - 1,90 (2H, m); of 3.95 (2H, t, J = 6,60 Hz); 4.09 to (2N, square, J = 7,33 Hz); of 6.26 (1H, s); 6.89 in (2H, DM, J = 8,80 Hz); 7,14 (2H, DM, J = 8,80 Hz); 7,26 - 7,40 (5H, m).

IR (l3)maxcm-1: 1770, 1610, 1510, 1370, 1290, 1260, 1240, 1170.

MS (m/z): 310 (M+) 268, 265, 238, 223, 196.

Getting 93. Ethyl (E)-3-(4-propoxyphenyl)cinnamate.

The compound was obtained as an oily substance with a yield of 35%.

NMR (CDCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = 7,33 Hz); of 1.10 (3H, t, J = 7,33 Hz); 1,75 - 1,90 (2H, m); to 3.92 (2H, t, J = 6,84 Hz); a 4.03 (2H, q, J = 7,33 Hz); 6,30 (1H, s); PC 6.82 (2H, DM, J = =9,27 Hz); 7,15 - 7,28 (2H, m); 7.23 percent (2H, DM, J= = 9,27 Hz); 7,28 - the 7.43 (3H, m).

IR (l3)maxcm-1: 1710, 1605, 1595, 1575, 1510, 1370, 1250, 1160, 1150.

MS (m/z): 310 (M+), 268, 265, 238, 223, 196.

Getting 94. (Z)-3-(4-propoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 93%, so pl. 183-185aboutC.

NMR (CDCl, 270 MHz) memorial plaques:="ptx2">

IR (l3)maxcm-1: 2400 - 3600 (Shir.), 1695, 1610, 1515, 1290, 1280, 1250, 1175.

MS (m/z): 282 (M+), 240, 223, 195.

Getting 95. (E)-3-(4-propoxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 92%, so pl. 138-140aboutC.

NMR (CDCl3, 60 MHz) M. D.: 1,0 (2H, t, J =7 Hz); 1,45 - of 2.20 (2H, m), 3,90 (2H, q, J = 7 Hz); 6,27 (1H, s); 6,83 (2H, DM, J = 9 Hz); 7,05 - of 7.60 (7H, m); 10,00 (1H, Shir. C.).

Getting 96. (E)-3-(3,4-methylenedioxyphenyl)cinnamic acid.

The compound was obtained as crystals after recrystallization from a mixture of diethyl ether and tetrahydrofuran to yield 22%, so pl. 222-224aboutC.

NMR (mixture 1:1 (by volume) CDCl3and CD3OD, 60 MHz) M. D.: of 5.99 (2H, s); of 6.29 (1H, s); 6,79 (3H, s); 7,05 - of 7.60 (5H, m).

Getting 97. (Z)-3-(3,4-methylenedioxyphenyl)cinnamic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) in 51% yield, 141-143aboutC.

NMR (CDCl3, 60 MHz) M. D.: 6,00 (2H, s); of 6.26 (1H, s); 6,72 - of 6.96 (3H, m); 7,15 - of 7.55 (5H, m).

Getting 98. Ethyl (E)-3-(3-methoxy-4-propoxyphenyl)-3- (3-were)acre - lat.

The connection was received in the form of the - ,95 (2H, m); 2,35 (3H, s); 3,81 (3H, s); 3,98 (2H, t, J = 6,84 Hz); Android 4.04 (2H, q, J = to 7.32 Hz); of 6.29 (1H, s); 6,72 - 6,86 (2H, m); 6.90 to (1H, Shir. C); 6,98 - 7,05 (2H, m); 7,15 - 7,24 (1H, m); 7,30 - 7,42 (1H, m).

IR (l3)maxcm-1: 1710, 1600, 1580, 1510, 1485, 1370, 1290, 1260, 1160, 1145, 1130.

MS (m/z): 354 (M+), 312, 267; 240.

Getting 99. Ethyl (Z)-3-(3-methoxy-4-propoxyphenyl)-3- (3-were)acre - lat.

The compound was obtained as an oily substance with a yield of 40%.

NMR (CDCl3, 270 MHz) M. D.: of 1.05 (3H, t, J = to 7.32 Hz); to 1.15 (3H, t, J = to 7.32 Hz); 1,80 - of 1.95 (2H, m); 2,32 (3H, s); of 3.80 (3H, s); was 4.02 (2H, t, J = 6,84 Hz); 4,08 (2H, q, J = to 7.32 Hz); of 6.26 (1H, d, J = 1,96 Hz); is 6.78 (1H, DD, J = 7,82 and 1.96 Hz); 6.87 in (1H, d, J = 7,82 Hz); 7,06 - of 7.25 (4H, m).

IR (Cl3)maxcm-1: 1710, 1605, 1590, 1515, 1465, 1370, 1250, 1180, 1160, 1130.

MS (m/z): 354 (M+), 312, 267, 240.

100. (E)-3-(3-methoxy-4-propoxy)-3- (3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 98%, so pl. 123-126aboutC.

NMR (CDCl3, 270 MHz) M. D.: of 1.03 (3H, t, J = 7,33 Hz); 1,75 - of 1.95 (2H, m); of 2.34 (3H, s); of 3.80 (3H, s); 3,98 (2H, t, J = 6,84); OF 6.26 (1H, s); 6,74 (1H, DD, J = 8,79 and 1,93 Hz); is 6.78 (1H, d, J = 8,79 Hz); 6,86 (1H, d, J = 1,95 Hz); 6,98 - 7,0 (2H, m); 7,14 - 7,30 (2H, m).

IR (l3)maxis the doctrine 101. Z-3-(3-methoxy-4-propoxyphenyl)-3- (3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) yield 97%, so pl. 132-135aboutC.

Getting 102. Ethyl 3,3-bis(3-were)acrylate.

The compound was obtained as an oily substance with a yield of 78%.

NMR (CDCl3, 270 MHz) M. D.: a 1.11 (3H, t, J = to 7.32 Hz); 2,32 (3H, s); 2,35 (3H, s); a 4.03 (2H, square, J = to 7.32 Hz); of 6.31 (1H, s); 6,98 - 7,30 (8H, m).

IR (l3)maxcm-1: 1710, 1620, 1600, 1580, 1370, 1350, 1280, 1190, 1160.

MS (m/z): 280 (M+), 265, 251, 235, 208.

Getting 103. 3,3-bis(3-were)acrylic acid.

The compound was obtained as crystals (after recrystallization from a mixture of methylene chloride and hexane) to yield 94%, so pl. 133-135aboutC.

NMR (CDCl3, 270 MHz) M. D.: 2,32 (3H, s); of 2.34 (3H, s); 6,28 (1H, s); 6,98 for 7.12 (4H, s); 7,14 - 7,30 (4H, m).

IR (l3) maxcm-1: 2400 - 3600 (Shir.), 1690, 1615, 1600, 1580, 1430, 1285, 1170.

MS (m/z): 252 (M+), 237, 235, 207.

Getting 104. Methyl (E)-3,5-diphenylene-2-EN-4-INOUT.

0,158 g of copper iodide and 0.424 g phenylacetylene was added to 25 ml of diethylamine containing 1,00 g of methyl(Z)-3-bromocinnamic and 0,029 g of bis(Triveni the tel drove away under reduced pressure. To the residue was added water, and the resulting mixture was extracted twice with benzene. The combined benzene extracts were washed with water, dried with anhydrous sodium sulfate, and are condensed by evaporation under reduced pressure. Then the residue was chromatographically on a column of silica gel (70 - 230 yler mesh, 25 g). These fractions were suirable mixture (39:1) of hexane and ethyl acetate, collected and received 1,043 g of target compound with so pl. 73-75aboutC (after recrystallization from hexane).

NMR (CDCl3, 270 MHz) M. D.: a-3.84 (3H, s); 6,0 (1H, s); 7,34 - of 7.82 (10H, m).

MS (m/z): 262 (M+), 247, 231.

IR (l3) maxcm-1: 2200, 1710, 1600, 1590, 1575, 1490, 1435, 1365, 1275, 1165.

Getting 105. (E)-3,5-diphenylene-2-EN-4-andnew acid.

A mixture of 1,000 g of methyl (E)-3,5-diphenylene-2-EN-4-ynoate (obtained in accordance with the description in getting 104), 15 ml of methanol and 7.5 ml of tetrahydrofuran and 15 ml of 10% aqueous sodium hydroxide solution was stirred for 18 h at room temperature. After this time the solvent is kept at reduced pressure. The obtained residue was diluted with water and was extracted twice with diethyl ether. Then the ether extracts were washed with water, dried with anhydrous target connection so pl. 124-126aboutAfter recrystallization from a mixture of methylene chloride and hexane.

NMR(CDCl3, 270 MHz) M. D.: of 6.65 (1H, s); 7,30 - of 7.90 (10H, m).

MS (m/z: 248 (M+), 231, 220.

IR (l3)maxcm-1: 2400 - 3600 Shire., 2200, 1685, 1600, 1590, 1575, 1490, 1450, 1280, 1180.

Getting 106. Ethyl 3,3-bis(4-methoxyphenyl)-3-hydroxy-2-methylpropionate.

A mixture of 8.25 g of ethyl 2-bromopropionate, 11,81 g of 4,4'-dimethoxybenzophenone, 7,16 g of zinc and 70 ml of benzene was heated on an oil bath for 4 h under reflux. Then the mixture was left to cool, after which the reaction solution was filtered. The filtrate is washed with 10% aqueous sulfuric acid, water and saturated aqueous sodium chloride, respectively. Then the mixture was dried, the solvent is kept at reduced pressure. The residue was subjected to flash chromatography on a column of silica gel (about 400 mesh, 300 g), and the fractions were suirable mixture (100:2) of hexane and ethyl acetate. As a result, we received a 7.92 g of target compound with so pl. 67-69aboutC (after recrystallization from a mixture of methylene chloride and hexane).

NMR (CDCl3, 270 MHz) M. D.: 1,14 (6N, t, J = 6,84 Hz); 3,54 (1H, q, J = 6,84 Hz); 3.75 to (6N, s); 3.95 to to 4.15 (2H, m); br4.61 (1H, s); to 6.80 (4H, DM, J = 8,79 Hz); 7,33 (2H, DM, J = 8,79 Hz); > 1710, 1610, 1510, 1460, 1375, 1340, 1245, 1170.

Elemental analysis of C20H24ABOUT5< / BR>
Calculated: 69,75%; N 7,02%.

Found: 69,89%; N 7,10%.

Getting 107. Ethyl 3,3-bis(4-methoxyphenyl)-2-methyl acrylate.

4,10 ml of phosphorus oxychloride was added drop by drop at 5-10aboutTo 140 ml of benzene solution containing 7,02 g of ethyl 3,3-bis(4-methoxyphenyl)-3-hydroxy-2-IU - dipropionate (obtained in accordance with the description in getting 106) at an oil bath. Then the reaction solution was stirred for 3 h at room temperature, after which it was poured into water and was extracted three times with diethyl ether. The combined ether extracts were washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride, then dried with anhydrous sodium sulfate, and are condensed by evaporation under reduced pressure. The residue (6,72 g) was subjected to column flash chromatography on silica gel (100 g), elwira with a mixture of hexane and ethyl acetate (95:5), resulting in a received 6,04 g of target compound in the form of an oily substance.

NMR (CDCl3, 270 MHz) M. D.: of 0.95 (3H, t, J = to 7.32 Hz); is 2.05 (3H, s); of 3.78 (2H, s); 3,81 (2H, s); of 3.97 (2H, q, J = to 7.32 Hz); 6,79 (2H, DM, J = = 8,30 Hz); 6,85 (2H, DM/SUB>)maxcm-1: 1700, 1610, 1510, 1465, 1315, 1300, 1280, 1240, 1175, 1125

Elemental analysis: C20H22ABOUT4< / BR>
Calculated: 73,60%; N 6,79%.

Found: 73,39%, N 6,82%.

Getting 108. 3,3-bis(4-methoxyphenyl)-2-methylacrylate acid.

The mixture 6,019 g of ethyl (3,3-bis(4-methoxyphenyl)acrylate (obtained according to the description in getting 107), 120 ml of ethanol and 80 ml of 10% aqueous sodium hydroxide solution was stirred for 14 h at room temperature. After this time the reaction mixture was heated on an oil bath at 100aboutC for 4 h, and the ethanol is then drove away. The residue was diluted with ice water and washed with ethyl acetate. Then the water phase was added one drop of concentrated hydrochloric acid to bring the pH to a value of 2. The aqueous phase was twice extracted with methylene chloride. United methylenechloride extracts were washed with water, dried with anhydrous sodium sulfate, and are condensed by evaporation under reduced pressure, resulting in a received 5,117 g of target compound in the form of crystals (so pl. 134-135about(C) (after recrystallization from a mixture of methylene chloride and hexane).

NMR (CDCl3, 270 MHz) memorial plaques: to 2.06 (3H, s); of 3.80 (3H, s); 3,81 (3H, s); 6,79 (2H, DM, J = 8,79 Hz); 6,86 (2H, )maxcm-1: 2400 - 3600 (Shir.), 1680, 1610, 1510, 1245, 1175.

Elemental analysis: C18H18O4< / BR>
Calculated: 72,47%; N, 6.08% In General.

Found: 72,11%; N 6,15%.

Getting 109. (Z)-(3,4,5-trimethoxybenzoyl)piperazine.

75 ml methylenchloride solution containing 7,40 g 3,4,5-trimethoxybenzaldehyde, was added drop by drop in 150 ml methylenchloride solution containing 3.80 g of N-formylpiperazine and 7,73 ml of triethylamine, in an ice bath. Then the mixture was stirred for 30 min at 0 to 5aboutWith, after which it was poured into water and was extracted twice with methylene chloride. United methylenechloride extracts washed with 10% aqueous hydrochloric acid and saturated aqueous sodium chloride, dried with anhydrous sodium sulfate, and are condensed by evaporation under reduced pressure. The residue (9,86 g) was dissolved in a mixture of 150 ml of tetrahydrofuran, 75 ml of methanol and 50 ml of 10% aqueous solution of sodium hydroxide, and then was stirred for 14 h at room temperature. After this time the reaction solution was poured into water and 4 times were extracted with methylene chloride. United methylenechloride extracts were washed with water, dried with anhydrous sulfate or acetate, resulting received 7,02 g of target compound in the form of crystals with so pl. 131-133aboutC.

NMR (CDCl3, 270 MHz) M. D.: 2,90 - 3,10 (8H, m); 3,91 (N, C); of 6.96 (2H, s).

MS (m/z): 316 (M+), 232, 85.

Elemental analysis: C13H20N2O5S

Calculated: 49,35%; N 6,37%, N Cent To 8.85%, S 10,13%.

Found: 49,62%; N, 6.30%, And; N 8,55%; S 10,11%.

Obtaining 110. 3,3-bis(3-chlorophenyl)acrylic acid.

Repeating the procedure in obtaining 1, except that used 10,85 g of 3,3-dichlorobenzophenone, resulting received 12,32 g of target compound with so pl. 114-115aboutC (after recrystallization from a mixture of methylene chloride and hexane).

Getting 111. 1-[3,3-bis(3-chlorophenyl)acryloyl]piperazine.

5,51 ml diphenylphosphinite and of 1.93 ml of N-formylpiperazine were added sequentially to a 100 ml of methylene chloride containing 5,00 3,3-bis(3-chlorophenyl)acrylic acid (obtained in accordance with the description in Getting 110) and of 4.75 g of triethylamine. Then the reaction mixture was stirred at room temperature for 18 h, after which it was washed with a saturated aqueous solution of sodium bicarbonate and then with water. Next, the mixture was dried with anhydrous sodium sulfate, and dissolve the furan, to it was added 50 ml of 10 wt./vol.% an aqueous solution of sodium hydroxide. The resulting mixture was stirred for 8 h at room temperature, after which it was poured into water. The solution was twice extracted with methylene chloride, the combined extracts were washed with water and dried with anhydrous sodium sulfate, then the solvent is kept at reduced pressure. The obtained residue was purified by column chromatography on silica gel (150 g), elwira mixtures of methylene chloride and methanol within 49:1 to 9:1 (by volume), resulting in a received 5,23 g of target compound in the form of a viscous oily substance.

NMR (CDCl3, 60 MHz) M. D.: of 2.21 (1H, BB); 2,00 - 2,95 (4H, m); 3,00 - of 3.85 (1H, m); 6,38 (1H, s); 6.90 to - 7,50 (8H, m).

MS (m/z): 360 (M+,35Cl), 325, 292, 275.

Getting 112. Ethyl (Z) and (E)-3-(2-naphthyl)-3-phenylacrylate.

Repeating the procedure described in the first part of getting 1, except that used 10,10 g-afterfinishing. The resulting crude compound was purified by column chromatography on silica gel (200 g), and then using liquid chromatography with moderate pressure using a column of Lobar and elwira mixtures of hexane and ethyl acetate. The result described is).

The re-elution with the same solvent received 4.44 g of E-isomer with so pl. 84-85aboutC (after recrystallization from hexane).

Getting 113. (Z)-3-(2-naphthyl)-3-phenylacrylate acid.

24 ml of a 10% aqueous solution of sodium hydroxide was added to the solution 2,411 g of ethyl (Z)-3-(2-naphthyl)-3-phenylacrylate (obtained according to the description in getting 112) in 48 ml of ethanol and 24 ml of tetrahydrofuran. The mixture was stirred for 15 h at room temperature, and then poured into water. the pH of the mixture was brought to 2 by adding concentrated hydrochloric acid, after which the mixture was twice extracted with methylene chloride. The combined extracts were washed with water and dried with anhydrous sodium sulfate, then the solvent was removed by evaporation under reduced pressure. The residue was recrystallized from a mixture of methylene chloride and hexane and received 2,005 g of target compound with so pl. 170-172aboutC.

NMR (mixture 1:1 (by volume) CDCl3and CD3OD, 60 MHz) M. D.: 6,44 (1H, s); 7,28 - 7,42 (6N, m); 7,44 - rate of 7.54 (2H, m); 7,71 (1H, d, J = 0,73 Hz); 7,76 - to $ 7.91 (3H, m).

MS (m/z): 274 (M+), 257, 229.

Elemental analysis: C19H14ABOUT2< / BR>
Calculated: 83,19%; N 5,14%

Found: 83,39%; N 5, the treatment 113, except that used 2,219 g of ethyl (E)-3-(2-naphthyl)-acrylate (obtained according to the description in getting 112), resulting in a received 1,685 g of target compound with so pl. 229-231aboutC (after recrystallization from a mixture of diethyl ether and tetrahydrofuran).

NMR (mixture 1:1 (by volume) CDCl3and CD3OD, 60 MHz) M. D.: 6,50 (1H, s); 7.23 percent - to 7.32 (2H, m); of 7.36 - the 7.43 (3H, m); 7,43 - rate of 7.54 (3H, m); to 7.67 (1H, d, J = 1,83 Hz); 7,70 - 7,88 (3H, m).

MS (m/z): 274 (M+), 257, 229.

Elemental analysis of C19H14ABOUT2< / BR>
Calculated 83,19%; N 5,14%.

Found: 83,45%, N 5,33%.

Getting 115. Ethyl (E)-p-isobutoxide.

13.8 g of potassium carbonate and 7.50 g of sodium iodide was added to the solution being 9.61 g of ethyl o-p-hydroxycinnamates and by 8.22 g isobutyramide in 100 ml of dimethyl sulfoxide. Then the reaction mixture was stirred for 20 h at 60aboutWith, after which it was cooled to room temperature. This reaction mixture was poured into 1 l of water and was extracted twice with ethyl acetate. The combined extracts were washed with water and dried with anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The residue was purified using flash column-chromatography on silica gel (300 g), elwira Akanistha substances, which was utverjdali at low temperature.

NMR (CDCl3, 60 MHz) M. D.: 0,98 (6N, d, J = 7 Hz); of 1.28 (3H, t, J = 7 Hz); 1,60 - 2,50 (1H, m), 3,70 (2H, d, J = 7 Hz); 4,24 (2H, q, J = 7 Hz); of 6.26 (1H, d, J = 16 Hz); 6,86 (2H, DM, J = 9 Hz); 7,45 (2H, DM, J = 9 Hz); 7,66 (1H, d, J = 16 Hz).

Getting 116. Ethyl (E)-p-propositional.

Repeating the procedure in obtaining 115, except that he used being 9.61 g of ethyl (E)-p-hydroxycinnamates and 10,20 g propyliodide, and sodium iodide was not used. Resulting received 11,00 g of target compound in the form of a solid substance.

NMR (CDCl3, 60 MHz) M. D.: and 0.98 (3H, t, J = 7 Hz); of 1.26 (3H, t, J = 7 Hz); 1,20 - 2,20 (2H, m), 3,88 (2H, t, J = 6.5 Hz); is 4.21 (2H, q, J = 7 Hz); 6,24 (1H, d, J = 16 Hz); 6,85 (2H, DM, J = 8 Hz); 7,44 (2H, DM, J = 8 Hz); a 7.62 (1H, d, J = 16 Hz).

Getting 117. Ethyl (E)-3,4-disproportionat.

Repeating the procedure in getting 116, but using 10,41 ethyl (E)-3,4-dihydroxycinnamate and 20,40 g propyliodide, resulting received and 10.20 g of target compound in the form of a solid substance.

NMR (CDCl3, 60 MHz) M. D.: 1,02 (6N, t, J = 7 Hz); of 1.32 (3H, t, J = 7 Hz); 1,50 - 2,20 (4H, m); 3,99 (4H, t, J = 7 Hz); 4.26 deaths (2H, square, 1 = 7 Hz); 6,30 (1H, d, J = 16 Hz); 6,70 - to 7.35 (3H, m); the 7.65 (1H, d, J = 16 Hz).

Getting 118. Ethyl (E)-4-ethoxy-3-methoxycinnamate.

NMR (CDCl3, 60 MHz) M. D.: of 1.30 (3H, t, J = 7 Hz); the 1.44 (3H, t, J = 7 Hz); the 3.89 (3H, s); to 4.14 (2H, q, J = 7 Hz); was 4.42 (2H, q, J = 7 Hz); 6,30 (1H, d, J = 16 Hz); 6,75 - to 7.35 (3H, m); 7,66 (1H, d, J = 7 Hz).

Getting 119. Ethyl (E)-3-methoxy-4-propositional.

Repeating the procedure in getting 116, but using 11.11 g of ethyl (E)-4-hydroxy-3-methoxycinnamate and 10,20 g propyliodide, resulting received 12,08 g of target compound.

NMR (CDCl3, 60 MHz) M. D.: a 1.01 (3H, t, J = 7 Hz); of 1.30 (3H, t, J = 7 Hz); 1,50 - 2,20 (2H, m), 3,88 (3H, s); 3,98 (2H, t, J = 7 Hz); 4,24 (2H, q, J = 7 Hz); 6,28 (1H, d, J = 16 Hz); 6,70 - to 7.35 (3H, m); the 7.65 (1H, d, J = 16 Hz).

Getting 120. Ethyl (E)-4-butoxy-3-methoxycinnamate.

Repeating the procedure in getting 116, but with the use of 6.66 g of ethyl (E)-4-hydroxy-3-methoxycinnamate and 6,62 g butylated, resulting received 7,00 g of target compound in the form of a solid substance.

NMR (CDCl3, 60 MHz) memorial plaques as 0.96 (3H, t, J = 7 Hz); of 1.30 (3H, t, J = 7 Hz); 1,20 - 2,10 (4H, m), 3,88 (3H, s); a 4.03 (3H, t, J = 7 Hz); 4,24 (2H, q, J = 7 Hz); 6,28 (1H, d, J = 16 Hz); 6,75 - to 7.35 (3H, m); the 7.65 (1H, d, J = 16 Hz).

Using the method of example obtaining 1 were obtained the compounds presented in the tion and purification, similar to example getting 111, using the compound of example getting 76 (5,65 g) are obtained in powder form specified in the header connection (6,37 g) so pl. 108-110aboutC.

NMR spectrum (270 MHz, CDCl3) memorial plaques: a 1.75 (1H, s), 2,35 at 2.45 (2H, s), 2,65 is 2.75 (2H, m), of 3.25 to 3.35 (2H, m), 3,45 - 3,55 (2H, m), 3,82 (3H, s); 6,28 (1H, s) 6,86 (2N, IR., J = 8,79 Hz), 7,16 and 7.36 (6N, m).

Elemental analysis for C20H21lN2O2< / BR>
Calculated: 67,32, N 5,93, N Of 7.85 CL To 9.93%.

Found: 67,09, N Of 5.81, N 7,81, CL 10,10%.

Getting 180. 4-Acetoxy-3,5-dimethoxybenzoic acid.

To a mixture of 3,5-dimethoxy-4-hydroxybenzoic acid (3 g) and acetic anhydride (30 ml) under ice cooling over 5 minutes added dropwise pyridine (15 ml). After stirring 30 min at room temperature, the reaction mixture was poured into water and stirred for 30 min at room temperature with subsequent threefold extraction with ethyl acetate. The combined extracts are washed with 10% hydrochloric acid, dried and concentrated. By recrystallization of the residue from a mixture of dichloromethane hexane get mentioned in the title compound (3.13 g), so pl. 192-194aboutC.

NMR spectrum (270 MHz, CDCl3) memorial plaques: a 2.36 (3H, s); 3.9 to (6N, (C), and 7.4 (2H, s).

The P CLASS="ptx2">

Getting 181. Ethyl ester of 3,5-dichloroamino acid.

To a mixture of sodium hydride (0.84 g, 55% dispersion in mineral oil) and tetrahydrofuran (40 ml) under cooling with ice up to 6-12aboutC for 12 min added dropwise ethyl ester diethylphosphonate acid (4,33 g) in tetrahydrofuran (20 ml). After stirring 30 min at room temperature to the mixture under ice cooling to 8 -11aboutC for 10 min added dropwise a solution of 3,5-dichlorobenzaldehyde (of 3.07 g) in tetrahydrofuran (20 ml). After stirring for 4 h at room temperature the reaction mixture was poured into water and extracted twice with ethyl acetate. The combined extracts washed with water, dried and concentrated. The residue is purified instant chromatography on silica gel (100 g). Faction, eluruume a mixture of hexane-ethyl acetate (99:1), collect and process, getting mentioned in the title compound (3.33 g), so pl. 71-73about(From cold hexane).

NMR spectrum (270 MHz, CDCl3) memorial plaques: to 1.34 (3H, t, J = to 7.32 Hz), 4,27 (2N, K, J = to 7.32 Hz), to 6.43 (1H, d, J = 16,11 Hz), was 7.36 (1H, t, J = =1,95 Hz); 7,38 (2H, d, J = 1,95 Hz), 7,54 (1H, d, J = 16,11 Hz).

Infrared absorption spectrum (l3)maxcm-1: 1770, 1640, 1580, 1560, 1415, 1360, 1310, 1280, 1270, 1170, 1020 +
,35CL), 216, 199, 171.

Calculated: 53,90, N 4,11, CL 28, 93%.

Found: 54,01, N 4,16, CL 28,76%.

Getting 182. Ethyl ester of 2,5-dichloroamino acid.

According to the method of obtaining 181, but using 2,5-dichlorobenzaldehyde (9,74 g) receive specified in the header connection (12,17 g), so pl. 34-36aboutC.

NMR spectrum (270 MHz, CDCl3) memorial plaques: is 1.35 (3H, t, J = to 7.32 Hz), 4,29 (2N, K, J = to 7.32 Hz), 6.42 per (1H, d, J = 16,12 Hz), 7,27 (1H, DV. D. J = 8,31 and of 2.44 Hz), 7,35 (1H, d, J = 8,30 Hz), to 7.59 (1H, d, J = 2,44 Hz), to 7.99 (1H, d, J = =16,12 Hz).

Mass spectrum (m/z: 244 (M+,35CL), 209, 199.

Elemental analysis for C11H10ABOUT2CL2< / BR>
Calculated: 53,90, N 4,11, Cl 28,93%.

Found: 54,14, N 4,24, CL 28,77%.

Getting 183. Ethyl ester of 2,3-dichloroamino acid.

According to the method of example obtaining 181, but using 2,3-dichlorobenzaldehyde (20 g) obtained specified in the header connection (23,46 g), so pl. 69-70aboutC (from hexane).

NMR spectrum (270 MHz, DCl3) memorial plaques: is 1.35 (3H, t, J = to 7.32 Hz), 4,29 (2n, K, J = to 7.32 Hz), 6,41 (1H, d, J = 16,12 Hz), 7,22 (1H, DV. d, J = = 8.30 and 8,30 Hz), of 7.48 (1H, DV. d, J = 8.30 and 1,47 Hz), 7,51 (1H, DV. d, J = 8.30 and 1,47 Hz), 8,08 (1H, d, J = 16,12 Hz).

Mass spectrum (m/z: 244 (M+, 35CL), 209, 199.

Elemental and 54,10, N Or 4.31, Cl 28,65%.

Getting 184. 1-[Z-3-(3,5-Dichlorophenyl)-3- (4-methoxyphenyl)acryloyl] Pipera-zine.

Using the reaction and purification similar to the procedures for obtaining 111, based on the compound of example getting 147 (1 g) obtained specified in the header connection (1,073) g) in powder form.

AMP-spectrum (270 MHz, DCl3) memorial plaques: 1,89 (1H, s), 2,45 - to 2.65 (2H, m), 2,65 - to 2.85 (2H, m), of 3.25 to 3.45 (2H, m), 3.45 points - of 3.65 (2H, m), 3,83 (3H, s), 6,33 (1H, s), 6.87 in (2N, IR. m, J = 8,79 Hz), 7,17 (2H, d, J = 1,95 Hz), 7,19 (2H, DV. m, J = 8,79 Hz), 7,35 (1H, t, J = 1,95 Hz).

Infrared absorption spectrum (l3)maxcm-1: 1630, 1610, 1565, 1515, 1465, 1445, 1250, 1180.

Mass spectrum (m/z): 390 (M+,35CL), 305,85.

Elemental analysis for C20H20CL2N2O2< / BR>
Calculated: 61,39, N 5,15, N 7,16, CL 18,12%.

Found: 61,44, N 5,39, N? 7.04 Baby Mortality, CL 17,93%.

Experiment 1. Inhibition F-induced hypotension.

As the test animals used rats Wictar-Imamici (each weighing from 350 to 450 g), anastasiosandy tool Inactin (90 mg/kg, intraperitoneally).

Throughout the experiment we measured blood pressure using a cannula introduced into the femoral artery. Each analyzed sample wodie have introduced l-Cl16:0F in the amount of 10 ng/kg per injection, until then, until I got a stable reaction. Then, intravenously was administered to each subject drug sample. After one minute was again introduced the same dose F. Drug sample was injected cumulative. On the basis of the degree of inhibition F-induced hypotensive actions were identified in 50% inhibitory dose (LD50), which is considered as the indicator F-antagonistic activity. For the introduction of animals PF was dissolved in physiological saline containing 0.25 wt.% of bovine serum albumin (BSA). Compound for injection was dissolved in dimethylformamide.

In addition to the compounds of the present invention in the described experiment was also tested well-known compound CV-3988, which was carried out under the same conditions, in order to illustrate the degree of increase in activity achieved with the present invention, compared with the most effective known connection. Connection CV-3988 described in U.S. patent - 4408052 and structurally is related F.

The results of the experiment are presented in table. 6. In this table, the compounds of the present invention PP vitro against F-induced platelet aggregation;

In rabbits took blood samples, which were mixed with 3.8 wt./vol.% aqueous solution of sodium citrate (1 h samples had 1/9 h solution). The samples were centrifuged (150 x G) at room temperature for 15 min to get from the upper layer fraction of plasma rich in platelets (R). Then the remains were centrifuged at 1000 x G for another 15 min to obtain the fraction of plasma poor in platelets (PPP), from the upper layer. Then R and PRP fractions appropriately mixed to obtain a sample in which a finite number of platelets was 6 x 1051 µl. Platelet aggregation was determined by the method of Born and others (Bornet al.: I. Physiol. 62, 67-68 (1962) to increase the transparency measured using aggregometry. To 272 μl of PRP was added 3 μl of a solution of the test compound in dimethyl sulfoxide, and then after 1 min was added 25 μl of saline solution containing l-C16:0F at a final concentration of 10-8- 3 x 10-8M. Inhibition of aggregation was observed within 5 minutes At the end of this period of time was determined by the degree of inhibition, which was calculated based on the last value and values F-induced aggregation, which was observed when using only a dime and "dose-effect".

The results are presented in table. 7.

Experiment 3. The inhibitory effect on the binding F receptors.

Blood samples were taken from the rabbit heart. 1 about.h. each sample was mixed with about 1/9. hours of 0.77 M solution of disodium ethylenediaminetetraacetate. Then repeated the procedure described in experiment 2, and received precipitated samples of platelets. These samples platelets were washed, after repeated operations of freezing and thawing for the destruction of cells were placed on top of the double layers consisting of 0.25 M and 1:5 M solution of sucrose. By centrifugation at is 63,500 x 6 for 2 h at 4aboutCollect the fraction obtained at the interface between 0.25 M and 1.5 M sucrose solutions, considered as the fraction F-receptor. Test for receptor binding was performed according to the technique very similar to the one described by Hwang and others [San-Bao Hwang et al: I. Biol. Chem. 260, 15639-15645 (1985)]. Specific binding3H-PAF was determined using Wattman filter GF/C. the Test compound was dissolved in dimethyl sulfoxide and 100-fold diluted buffer solution containing 0.5% bovine serum albumin. In this experiment, for mixing the used ratio: one part of the solution tested SOEDINENIYa from the graph curve linear relationship between the logarithm of the concentration of the test compound and 50% inhibitory concentration (IC50).

The results of the experiment are presented in table. 8.

Derivatives of N-acryloylmorpholine of the present invention showed excellent F-antagonistic activity.

Experiment 4. Acute toxicity. Each group, consisting of 3 mice (males) by 5 weeks of age, were administered orally each of the compounds obtained in accordance with the description in examples 2, 7 and 15 at a dose of 300 mg/kg Mice were observed for 1 week, and during this period, all mice survived that clearly illustrates the very low toxicity of the compounds of the present invention.

The METHOD of OBTAINING DERIVATIVES of N-ACRYLOYLMORPHOLINE General formula

CCHNR3< / BR>
where R1and R2- same or different, phenyl, unsubstituted or substituted by 1-2 substituents selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, trifloromethyl or ceanography, or naphthyl, or titillation;

n is an integer 2 or 3;

R3- C1-C4-alkoxygroup or one of R3the hydroxy - group and the remaining R3-C1-C4-alkoxygroup,

characterized in that the compound of General formula

CCHZ1< / BR>
where R1and R2have the specified values,

one of Z1and Z2- nucleophilic deleted the group and the other group of the formula

NH

where n=2,3.

 

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FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to N-(indolcarbonyl)piperazine derivatives of general formula I

, wherein R1 is optionally substituted phenyl or naphthyl; R2 and R3 are independently Hal or Het1, A, OA, CN; R4 is H, CN, acyl, Hal, CONH2, CONHA or CONA; R1 is H; or R4 and R5 together form C3-C5-group; Het1 is aromatic heterocyclic ring, optionally substituted with one or two halogen atoms and containing 1-3 similar or different heteroatoms such as nitrogen, sulfur and oxygen, A-(C1-C6)-alkyl; Hal is F, Cl,Br, and J; and indole ring may be substituted with isatin, except for (1H-indole-5-yl)-(4-phenethylpiperazine-1-yl)-methanone and 1-((5-methoxy-1H-indole-7-yl)-carbonyl)-4-(2-phenethyl)-piperazine. Claimed compounds are potent 5-HT2A antagonists and are useful in treatment of psychosis, schizophrenia, depression, neurological diseases, dismepodia, Parlinson's disease, Alzheimer's disease, Hungtington's disease, amyotrophic lateral sclerosis, bulimia or anorexia, premenstrual syndrome, and/or in alleviation of hypomania.

EFFECT: new pharmaceutical agents.

9 cl, 10 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of adamantane of the general formula:

wherein m = 1 or 2; each R1 represents independently hydrogen atom; A represents C(O)NH or NHC(O); Ar represents the group:

or

wherein X represents a bond, oxygen atom or group CO, (CH2)1-6, CH=, O(CH2)1-6, O(CH2)2-6O, O(CH2)2-3O(CH2)1-3, CR'(OH), NR5, (CH2)1-6NR5, CONR5, S(O)n, S(O)nCH2, CH2S(O)n wherein n = 0, 1 or 2; R' represents hydrogen atom; one of R2 and R3 represents halogen atom, nitro-group, (C1-C6)-alkyl; and another is taken among R2 and R3 and represents hydrogen or halogen atom; either R4 represents 3-9-membered saturated or unsaturated aliphatic heterocyclic ring system comprising one or two nitrogen atoms and oxygen atom optionally being heterocyclic ring system is substituted optionally with one or more substitutes taken independently among hydroxyl atoms, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, -NR6R7, -(CH2)rNR6R7; or R4 represents 3-8-membered saturated carbocyclic ring system substituted with one or more substitutes taken independently among -NR6R7, -(CH2)NR6R7 wherein r = 1; R5 represents hydrogen atom; R6 and R7 each represents independently hydrogen atom or (C1-C6)-alkyl, or (C2-C6)-hydroxyalkyl group eliciting antagonistic effect with respect to R2X7-receptors. Also, invention describes a method for their preparing, pharmaceutical composition comprising thereof, a method for preparing the pharmaceutical composition and their applying in therapy for treatment of rheumatic arthritis and obstructive diseases of respiratory ways.

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

13 cl, 88 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of formula I , wherein G is carbon or nitrogen atom; A is i) phenyl substituted with any from -COOH, -CONH2, COOCH3, -CN, -NH2 or -COCH3; ii) naphthyl, benzophuranyl, and quinolinyl; and iii) formulae , , .

Compounds of present invention are useful in particular in pain treatment.

EFFECT: new agents for pain treatment.

58 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel soluble pharmaceutical salts formed from salt-forming active compound of the general formula (I) or (II) and sugar substitute that can be used in preparing medicinal agents useful in pain and enuresis treatment. Salt-forming active substance represents a salt-forming compound among 1-phenyl-3-dimethylaminopropane compounds of the general formula (I) wherein X means -OH, F, Cl, H or group -OCOR6; R1 represents (C1-C4)-alkyl group; R2 represents H or (C1-C4)-alkyl group; R3 represents H or (C1-C4)-alkyl group with a direct chain, or R2 and R3 form in common (C4-C7)-cycloalkyl group and if R5 means H then R4 represents group O-Z in meta-position wherein Z means H,(C1-C3)-alkyl, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl), -CONH-C6H4-(C1-C3-alkyl), -CO-C6H4-R7 wherein R7 represents -OCO-C1-C3-alkyl in ortho-position or group -CH2N(R8)2 in meta- or para-position and wherein R8 means (C1-C4)-alkyl or 4-morpholino-group, either R4 represents S-(C1-C3)-alkyl in meta-position, meta-Cl, meta-F, group -CR9R10R11 in meta-position wherein R9, R10 and R11 mean H or F, group -OH in ortho-position, O-(C2-C3)-alkyl in ortho-position, para-F or group -CR9R10R11 in para-position wherein R9, R10 and R11 mean H or F, or if R5 means Cl, F, group -OH or O-C1-C3-alkyl in para-position then R4 means Cl, F, group -OH or O-(C1-C3)-alkyl in meta-position, or R4 and R5 form in common group 3,4-OCH=CH- or OCH=CHO-; R6 means (C1-C3)-alkyl, or salt-forming active substance represents a salt-forming compound among 6-dimethylaminomethyl-1-phenylcyclohexane compounds of the general formula (II) wherein R1' represents H, -OH, Cl or F; R2' and R3' have similar or different values and represent H, (C1-C4)-alkyl, benzyl, -CF3, -OH, -OCH2-C6H5, O-(C1-C4)-alkyl, Cl or F under condition that at least one among radicals R2' either R3' means H; R4' represents H, -CH3, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl, -CO-NH-C6H4-(C1-C3)-alkyl, -CO-C6H4-R5', CO-(C1-C5)-alkyl), -CO-CHR6'-NHR7' or unsubstituted either substituted pyridyl, thienyl, thiazolyl or phenyl group; R5' represents -OC(O)-(C1-C3)-alkyl in ortho-position or -CH2N(R8')2 in meta- or para-position and wherein R8' means (C1-C4)-alkyl, or both radicals R8' in common with nitrogen atom (N) form 4-morpholino-group, and R6' and R7' have similar or different values and represent H or (C1-C6)-alkyl under condition that if both radicals R2' and R3' represent H then R4' doesn't mean -CH3 when R1' represents additionally H, -OH or Cl, either R4' doesn't mean H when R1' represents additionally -OH. Also, invention relates to a medicinal agent based on indicated salts.

EFFECT: valuable medicinal properties of salts and drug.

14 cl, 1 tbl, 8 ex

FIELD: organic chemistry, biochemistry, enzymes.

SUBSTANCE: invention relates to compounds represented by the formula: wherein values of substitutes are given in the invention description. Also, invention relates to pharmaceutically acceptable salts of the compound that can be used in treatment and/or prophylaxis of cathepsin-dependent states or diseases of mammals. Proposed compound are useful in treatment of diseases wherein bone resorption inhibition is desired, such as osteoporosis, increased mineral density of bone and reducing risk of fractures. Proposed claimed compounds are designated for preparing a drug possessing the inhibitory activity with respect to cathepsin.

EFFECT: valuable medicinal and biochemical properties of compounds.

24 cl, 13 sch, 4 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: invention relates to aryl or heteroarylpiperazines with general formula II , where R2 is hydrogen or C1-4-alkyl (i) R1 is branched C4-6-alkyl, branched C4-6-alkenyl or branched C4-6-alkynyl, under the condition that R1 is not isobutyl, - C3-5-cycloalkyl, C3-7-cycloalkenyl, C3-6-cycloalkyl-C1-3-alkyl or C3-6-cycloalkenyl-C1-3-alkyl, -R1 and R2 together form a C3-6-alkylene bridge, and A is or or (ii) R1 - is ethyl, n-propyl or isopropyl, - R1 and R2 together form a C3-6-alkylene bridge, and A is or . Described also is a pharmaceutical composition based on formula II compounds, use of formula II compounds and method of treatment.

EFFECT: compounds exhibit high and selective bonding affinity to histamine H3 receptor and can be used for treating diseases and disorders, related to histamine H3 receptor.

49 cl, 149 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel nonsteroid synthetic derivatives with the following structures or their pharmaceutically acceptable salts:

, , ,

,

or

, which are capable of modulating the androgen receptor.

EFFECT: invention relates to pharmaceutical compositions containing said derivatives and use thereof to make nonsteroid medicinal agents for treating and/or preventing conditions or diseases such as prostate hyperplasia, prostate cancer, hirsutism, severe hormone-dependant alopecia or acne etc, resulting from antagonistic activity towards the androgen receptor.

6 cl, 5 dwg, 3 tbl,12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 3-substituted 4-(phenyl-N-alkyl)piperazine compounds of formula (1) , where R1 represents OSO2CF3, OSO2CH3, SO2R3, COCF3 and COCH2CH3, R2 represents C1-C4 alkyl or allyl, R3 represents C1-C3 alkyl or CF3, as well as to their pharmaceutically acceptable salts. The disclosed compounds are capable of modulating dopamine neurotransmission.

EFFECT: invention discloses pharmaceutical compositions of compounds which are used for treating disorders of the central nervous system.

4 cl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely new organic compounds, namely N,N'-substituted piperazines of general formula (I), wherein R1, R2: linear or branched alkoxy (C1÷C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; X:C(=NH)NH2, C(=NH)NHC(-NH)NH2, G is low-molecular organic or mineral acid, sodium, potassium, ammonium cations or water influences the haemostasis system, showing antiagregant, anticoagulant and vasodilator properties, and to a method for preparing N,N'-substituted piperazines of formula 1 by reaction of N-substituted piperazines of general formula wherein R1, R2; linear or branched alkoxy (C1÷C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; and 1H-pyrazole-1-carboxamidine, dicyane diamide and their salts in organic solvents or water at temperature 10-50°C in the presence of bases.

EFFECT: new substance are promising for prevention and treatment of the disturbed haemostasis system.

12 cl, 10 tbl, 14 ex

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