Derivatives piperazinylmethyl or their salts, having the property of braking withdrawal syndrome
(57) Abstract:Usage: in medicine as a treatment for withdrawal symptoms. The inventive products: derivatives piperazinylmethyl formula where n is an integer from 1 to 6; R is hydrogen, halogen, C1-C4- alkyl, heteroaryl, sulfonyl, mono - or disubstituted sulfa group, nitro, hydroxy, oxo, C1-C4- alkoxy, cyano, C1-C4alkylcarboxylic group, unsubstituted or substituted aryl, amino or substituted amino group. Reagent I where X is a halogen. Reagent 2: where R has the above meanings reaction Conditions: in a medium of an organic solvent in the presence of a base. 6 table. The invention relates to new derivatives of 1H-azole-( -4-1-(2-pyrimidinyl)-piperazinil)-alkyl, and their physiologically acceptable salts, intended for the treatment of disorders associated with withdrawal syndrome induced by the removal of benzodiazepines, particularly diazepam, cocaine, alcohol and/or nicotine.At that time, known as anxiolytics  always be not able to inhibit withdrawal syndrome, was completely unexpected that some derivatives of 1H-azole-( -(4-(2-tx2">Compounds according to the invention correspond to General formula I
NN(CH2)n-N (l) where n can have values from 1 to 6 and R represents a hydrogen atom, halogen, lower alkyl with C1-C4the radical heteroaryl, sulfonovy radical, substituted N-sulfamerazine or disubstituted N-sulfamerazine, a nitro radical, a hydroxy radical, an oxo radical, lower alkoxy radical with C1-C4, a cyano radical, a lower radical alkylcarboxylic with1-C4the radical aryl or substituted aryl radical, the radical is amino or substituted amino radical of the formula
-N where R1and R2identical or different, represent a hydrogen atom, alkyl radical, aryl radical, the radical of alkylcarboxylic, radical, arylcarbamoyl, alkylsulfonyl radical or a radical arylsulfonyl, fragments of these alkyl radicals containing 1-4 carbon atoms.These derivatives of General formula I can be obtained by one of the following methods.Method AND
By the reaction of one of the compounds of General formula II
NN(CH2)n-X (ll) where X represents halogenatom or a group chosen among tosyloxy or mesilate one compound of General formula III
HN (lll) where R is viewpo is insulted, of dimethylformamide, alcohol, aromatic or non-aromatic hydrocarbon, ether such as dioxane or diphenyl ether, or in the presence of a mixture of these solvents. Mainly, this reaction is conducted in the presence of a single base, such as hydroxides, carbonates or bicarbonates of alkali metals, or in the presence of a mixture of these bases. The most appropriate temperature range from ambient temperature to the reflux temperature of the solvent, and the reaction time is from 1 to 24 hoursMethod C.By restoring one of the compounds of General formula I, in which R represents a nitro group.Among the numerous reducing agents that can be used to restore one nitro group of one amino group include the following reducing agents: catalytic hydrogenation using catalysts of Nickel, palladium or platinum, is an amalgam of zinc with hydrochloric acid, borhydride alkali metals, etc.The reaction is carried out in such one alcohol, like methanol, ethanol or in one of propanolol or butanol, or mixtures of one of the alcohol with water. Most adeci is from 1 to 24 hoursMethod
By acylation of one of the compounds of General formula I, in which R represents an amino group of one acid halide or anhydride.The reaction is carried out without solvent or in the presence of one adequate solvent, such as hydrocarbon, ketone or ether, in the presence of a single base, such as pyridine or trialkylamine. The most appropriate temperature range from -10aboutC to the boiling point of the solvent, and the reaction time is from 1 to 24 hoursMethod D
By alkylated recovery of one of the compounds of General formula I, in which R represents a nitro group, and it alkilirovanie recovery is performed with alkali metal borohydride in the presence of Nickel chloride II and one of the compounds having the group of the ketone or aldehyde. This reaction is carried out in alcohol or in a mixture of alcohol and water. The most suitable temperatures are temperatures from -15aboutC to the reflux temperature of the solvent, and the reaction time is from several minutes to 24 hoursMethod E
By the reaction of one of the compounds of General formula IV
X-(CH2)n-N (lV) where X and n incasino getting some derivatives in the framework of the present invention. Also describes some applications.Method AND
P R I m e R 1. Obtaining 1H-pyrazole-1-(4-(-4(2-pyrimidinyl)-1-piperazinyl)-Boo").Heated at reflux for 14 h the mixture of 4 g (13.3 mmol) of 2-pyrimidine-1-(4-bromobutyl)-4-piperazine, of 1.02 g (15 mmol) of pyrazole and 2.76 g (20 mmol) of potassium carbonate in 50 ml of dimethylformamide. Evaporated in vacuo, add chloroform, washed with water, dried on sodium sulfate, evaporated in vacuo and obtain 3.5 g of oil, which is 1H-pyrazole-1-(4-(4-(2-pyrimidinyl)-1-piperazinil)-butyl).Compounds identified by examples 2-9, get in the same way as data for identifying lead in the table.1.Method IN
P R I m e R 10. Obtaining 1H-pyrazole-4-amino-1-(4-(4-(2-pyrimidinyl)-1-piperazin - nil)-butyl).Added 10.2 g (43.2 mmol) of hexahydrotriazine Nickel II in a solution of 7.2 g (21 mmol) of 1H-pyrazole-4-nitro-1-(4-(4-(2-pyrimidinyl)-1-piperazinil)-butyl) (example 7) in 60 ml of ethanol with vigorous stirring. Cooled in the ice bath and slowly added 10.2 g (81 mmol) of sodium borohydride. Left under stirring for 1 h, and after 1 h at ambient temperature, water is added, evaporated in vacuo, acidified with concentrated is om. Thus, the gain of 4.4 g of 1H-pyrazole-4-amino-1-(4-(4-(2-pyrimidinyl)- 1-piperazinil)-butyl) in liquid form.Spectroscopic data for the identification of lead in the table.2.Method
P R I m e R 11. Obtaining 1H-pyrazole-4-methylsulfonylamino-1-(4-(4-(2-pyrimidinyl)-1-piperazinil)-butyl ).Slowly add 1.8 g (16 mmol) of methanesulfonamide to the cooled solution of 4.4 g (14.6 mmol) of 1H-pyrazole-4-amino-1-(4-(4-(2-pyrimidinyl)-1-piperazinil)-butyl) (example 16) in 30 ml of pyridine. Leave for 1 h at 0aboutWith leave at ambient temperature for 4 h, poured into ice water, extracted with chloroform and obtain 3.7 g of 1H-pyrazole-4-methyl-sulphonamido-1-(4-(4-(2-pyrimidinyl)-1-piperazinil)-butyl), which can be recrystallizing in ethyl ether with a melting point of 132aboutC.Compounds identified by examples 12 and 13 receive the same method and data to identify lead in the table.2.Method D
P R I m e R 14. Obtaining 1H-pyrazole-4-(2-butyl)amino-1-(4-(-4(2-pyrimidinyl)-1 - piperazinil)-butyl).Add 0.9 g (24 mmol) of sodium borohydride in a suspension of 2.8 g (12 mmol) of hexahydrotriazine Nickel in a solution of 2 g (6 mmol) of 1H-piraso to 0aboutC. Maintain this temperature for 30 min, leave the mixture to rise at room temperature, continue stirring for 2 h, evaporated in vacuo, absorb with ethyl acetate and obtain 1.22 g of 1H-pyrazole-4-(2-butyl)amino-1-(4-(4-(2-pyrimidinyl)-1-Pipera - sinil)-butyl) in liquid form.Spectroscopic data of this product indicated in the table.2.The study of anxiolytic or concern activity in mice
Use a test light and dark boxes (J. Phar. Pharmacol, 1988, 40, p. 494-500). The mouse is placed in a light area of a box divided into two compartments: one strongly lit, light box, and other poorly lit, dark box.Count the number of times the mouse rises on its hind legs in each compartment within 5 minutes (see column 2, table. 3-6).Activity in each compartment is given by counting the number of re-baptizing cells, which constitute separate each compartment (see column 3, table.3-6).Measure the time spent in the dark box for 5 minutes countdown (see column 4, table.3-6).Determine the source of the latency, i.e. the time elapsed from the premises of the animal in the light box, in the start of the test until it povedenie mice during different periods of treatment, always comparing it with the behavior of groups of control animals not subjected to any processing.Treatment and experimental scheme
The dependence of a particular treatment (diazepam, cocaine, alcohol or nicotine) by daily injection over a period of 7 or 14 days. This processing causes anxiolytic response response (increased activity and are present in a light box).Dosage:
diazepam: 10 mg/kg i.p. 2 times a day for 7 days;
cocaine: 1 kg/kg i.p. within 14 days;
the alcohol is introduced at a rate of 8% weight/volume in drinking water for 14 days;
nicotine: 0.1 mg/kg i.p. 2 times a day for 14 days.Stop treatment for 24 h causes a withdrawal syndrome, which manifests as akcionerna response (increases the activity and presence in the black box).3) various Other groups in addition to get diazepam, cocaine, alcohol or nicotine related processing products, which are the objects of the present invention in comparison with buspirone or ipsapirone. These groups are also exempt from treatment with diazepam, cocaine, alcohol or nicotine, and there is also a return reacts the l-4-chloro-1-(4-(4-(2-pyrimide-nil)-1-piperazinil)-butyl) (example 4): 0.5 mg/kg i.p. 2 times a day;
1H-pyrazole-1-(4-(4-(2-pyrimidinyl)1-piperazinil)-butyl) (example 1): 0.5 mg/kg i. p. 2 times a day; 1H-pyrazole-4-methylsulfonylamino-1-(4-(4-(2-pyrimidinyl)-1-piperazinil)-butyl (example 11): 1 mg/kg i.p. 2 times a day (compared to diazepam, alcohol and nicotine) and 0.5 mg/kg i.p. 2 times a day (in relation to cocaine).The observed results are shown in table.3-6.The following reaction products, which are the objects of the invention:
Produced by examples 1 and 4 inhibit withdrawal syndrome, which manifests as entries response, inductively diazepam, cocaine, alcohol and nicotine, and in addition they hold a significant anxiolytic response, when stop the introduction of diazepam, cocaine, alcohol or nicotine.Derivatives with respect to example 11 inhibit withdrawal syndrome, which manifests as entries response, inductively diazepam, alcohol and nicotine, and, in addition, they hold a significant anxiolytic response, when stop the introduction of diazepam and alcohol.Buspirone saves withdrawal syndrome, which manifests as entries response, range of complete scientolo syndrome, and anxiogenic. Buspirone hampers only some parameters entries response after stopping treatment with alcohol.Ipsapirone saves withdrawal syndrome, which manifests as entries response, inductively diazepam, cocaine and nicotine. Ipsapirone inhibits withdrawal syndrome, which manifests itself in the form of entries reaction inductional alcohol.Therefore, derivatives of General formula I according to the invention are useful as active compounds in medicaments for the treatment of disorders associated with withdrawal syndrome, which is manifested, in particular, in the form of entries of the reaction, inductional abrupt elimination of prolonged treatment with benzodiazepines such as diazepam, cocaine or prolonged absorption of alcohol and/or nicotine.In human therapy, the dose of the introduction of course depends on serious syndrome.It usually is about 5-100 mg/day.Derivatives of the invention are introduced, for example, in the form of tablets, solutions or suspensions, or in the form of gelatin capsules.As examples BR>Microcrystalline
nirovany starch 3
Colloidal silicon dioxide 1
Weight tablets 100
The reception of tablets:
Mix in the mixer connection I, lactose and pre gelatinizing starch to a homogeneous state. The resulting mixture was mixed with an ethanol solution of povidone. Dried in an oven at 50aboutWith over 10 hours Granularit through a sieve with an aperture of 1 mm, Determine the weight of the granules and mixed with microcrystalline cellulose and colloidal silicon dioxide to a homogeneous state. Add magnesium stearate and mix for no more than 5 minutes Take a sample and analyze. After analysis of pressed pellets in a pressing machine and get a tablet with a theoretical weight of 100 mg (boundary settings according to Ph.Eur.). A sample is taken for final inspection.An example formula for Gelati-
had been forecast capsules mg
Compound IV 10
Beginat glycerin 5
Excipient: soft gelatin in sufficient quantity.An example of obtaining generalplan mix. In the resulting mixture was heated to 45-55aboutWith injected under stirring compound IV, and continue stirring until a homogeneous state. The mixture is allowed to cool with stirring and then when you reach the desired consistency change anchor stirrer. Continue cooling to 25aboutAnd then the stirring is stopped. Select a sample for analysis. After the establishment of the analysis carried out, the addition of fillers. To this stirred while melting the following softening ingredients: gelatin, glycerin, pigment and purified water. Transfer the mixture into the funnel filler machine, equipped with soft mixing. Batched together the mixture and a soft gelatin shell so that the weight of the capsules were in the following ranges:
Theoretical weight: 150 mg (standard for Ph. Eur.)
Total weight: 200 mg ( 5%).Washed obtained capsules and dried. Select samples for final inspection. Derivatives piperazinylmethyl General formula
< / BR>where n is an integer from 1 to 6;
R is hydrogen, halogen, C1-C4-alkyl, sulfonyl, mono - or disubstituted sulfa group, nitro, hydroxy, oxo, C1-C4-alkoxy, cyano, C1-C4alkylcarboxylic 1 and R2the same or different, hydrogen, alkyl, alkylcarboxylic, alkylsulfonyl containing 1 to 4 carbon atoms in the alkyl, phenyl, phenylcarbene or phenylsulfonyl,
or their salts, having the property of braking withdrawal syndrome.
CH= NNH< / BR>This connection can be used as Magenta masking components (H-688)
FIELD: organic chemistry, fungicides, agriculture.
SUBSTANCE: invention describes pyrazolcarboxamide of the formula (I) wherein if X means oxygen atom (O) then R1 represents (C1-C3)-alkoxy-(C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means fluorine (F), chlorine (Cl) or bromine atom (Br), and if X means sulfur atom (S) then R1 means (C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means halogen atom. Also, invention describes a method for preparing compounds of the formula (I), a composition for control of microorganisms and prevention for their attack and damage of plants, and a method for control of phytopathogen organisms, and compound of the formula (V) wherein X means sulfur atom (S); R1 means (C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means chlorine, bromide or iodine atom. Invention provides control and prevention in infection of plants with phytopathogenic microorganisms - fungi in agriculture and horticulture.
EFFECT: valuable agricultural properties of compounds.
9 cl, 4 tbl, 12 ex
FIELD: organic chemistry, agriculture, insecticides.
SUBSTANCE: invention relates to a substituted anilide derivative of the formula (I): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2; Z represents oxygen atom; Q means a substitute represented by any of the following formulae: Q1-Q3, Q6, Q8-Q12, Q14-Q19, Q21 and Q23 (wherein each among Y1 that can be similar or different represents halogen atom, (C1-C6)-alkyl group, and so on); Y2 represents (C1-C6)-alkyl group or halogen-(C1-C6)-alkyl group; Y3 represents (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl group or substituted phenyl group; p represents a whole number from 1 to 2; q represents a whole number from 0 or 2; r represents a whole number from 0 to 2. Also, invention proposes a chemical for control of pests of agricultural and fruit crops. The chemical comprises substituted anilide derivative of the formula (I) as an active component and represents insecticide, fungicide or acaricide. Also, invention proposes a method for addition of the chemical for control of pests of agricultural and fruits crops. Also, invention proposes aniline derivative represented by the general formula (II): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2. Invention provides the development of anilide derivative as insecticide, fungicide and acaricide against pests of agricultural and fruit crops.
EFFECT: valuable properties of compound.
5 cl, 6 tbl, 27 ex
FIELD: organic chemistry, insecticides.
SUBSTANCE: invention relates to compounds of the formula (1) , their N-oxides and salts that can be used in agriculture wherein values A, B, J, R1, R3, R4 and n are given in the invention claim. Also, invention describes a method for control of arthropoda pests to provides high productivity that comprises applying the effective dose of compound of the formula (1) on arthropoda pests and in medium of their habitation, and a the composition with arthropocide activity comprising compounds of the formula (1).
EFFECT: valuable properties of compounds and composition.
23 cl, 34 tbl, 759 ex
FIELD: organic chemistry, fungicides.
SUBSTANCE: invention describes pyrazolylcarboxanilides of the formula (I) wherein R means difluoromethyl or trifluoromethyl group; R1 and R2 mean independently of one another halogen atom or (C1-C6)-alkyl; R3 means fluorine atom, and agent and method for control of undesirable fungi using compounds of the formula (I), and novel intermediate substances - derivatives of aniline and halogenpyrazolcarboxanilides. Compounds of the formula (I) elicit fungicide properties and can be used in protection of plants.
EFFECT: valuable properties of compounds and agent.
15 cl, 8 tbl, 10 ex
SUBSTANCE: the said invention relates to о-cyclopropylcarboxanilides of general formula (I) , where Het stands for pyrrolyl, pyrazolyl or thiazolyl, each being substituted with R4, R5 and R6 groups; R1, RЗ stand for hydrogen or halogen; R3 stands for С2-12 alkyl, С3-12 cycloalkyl, С3-12 cycloalkyl substituted with С1-3 alkyl, phenyl or halogen-substituted phenyl; and R4, R5 and R6 are independently selected from hydrogen, halogen, С1-4 alkyl or С1-4 haloalkyl, provided that at least one of R4, R5 and R6 is other than hydrogen. Intermediates used in synthesis of I, as well as antimicrobial composition and methods for control and prevention of cultivated plants' infection with phytopathogenic microorganisms are described.
EFFECT: compounds can be used to protect plants from being infected with phytopathogenic microorganisms.
8 cl, 7 tbl, 12 ex
SUBSTANCE: invention refers to the method of preparation of 3-halogen-4.5-dihydro-1H-pyrasol compound of the formula , it includes interreaction with HX1of other 4.5-dihydro-1H-pyrasol compound of the formula , in which X1 is halogen and R3, R4, Z, n and X2 have values given in the description. The invention also describes preparation of the compounds of the formula , in which X1, R3, R6, R7, R8a, R8b and n have values, which are indicated in the description, in terms of the formula (Ia) of the compound, prepared according to p.1 of the invention formula.
EFFECT: development of the alternative method of preparation of the compounds with using reagent of relatively low price.
9 cl, 1 tbl, 4 ex, 9 dwg
SUBSTANCE: aim of the invention is to create a method of obtaining a compound with general formula I , in which R1 represents a hydrogen atom or halogen or (C1-C4)alkene group; R2, R3, R4, R5, R6, R7 each independently represents a hydrogen atom or halogen or (C1-C4)alkene, (C1-C4)alkoxy, trifluoromethyl group as well as its salts. The proposed method involves reaction of a pentane derivative with formula X-(CH2)5-X'(II), in which each of X and X' independently represent a halogen atom or YSO2O- group, in which Y represents (C1-C4)alkene, (C1-C4)perfluoroalkene, phenyl group, unsubstituted or substituted with methyl, chloro- or a nitro- group, and the corresponding derivative of pyrazole-3-carbohydrazide. The invention also pertains to the method of obtaining N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant) and its salts.
EFFECT: development of an alternative method of obtaining formula I compounds and, in particular, pure rimonabant, which shows activity in clinic in obesity and smoking addiction.
11 cl, 1 ex
FIELD: chemistry, pharmacology.
SUBSTANCE: invention relates to novel compounds -acidified arylcycloalkylamins of formula I in any of their stereoisomeric forms or in form of their mixture in any ratio, or their pharmaceutically acceptable salts, where in formula I : R1 represents aryl, not obligatory substituted with one or two similar or different substitutes, selected from group that includes C1-C6-alkyl and halogen; R2 represents aryl or heteroaryl, which represents residue of 5-6-member aromatic monocyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom and/or 1 sulfur atom or oxygen atom, or residue of 9-10-member aromatic bicyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom, each of which is unsubstituted or contains 1-3 similar or different substitutes, selected from group, consisting of halogens, NH2, unsubstituted C1-C10-alkyl, C1-C10 -alcoxy, C1-C10-alkylamino and di(C1-C10-alkyl)amino, and at least monosubstituted C1-C10-alkyl, etc., n represents 1, 2, 3 or 4. Invention relates to pharmaceutical composition, stimulating expression of endothelial NO synthase, based on said compounds, as well as application of compounds of formula I for production of medication for stimulating expression of endothelial NO-synthase and for treatment of such cardiovascular diseases as atherosclerosis, thrombosis, coronary artery disease, hypertension and impaired cardiac function.
EFFECT: invention ensures enhancing composition and treatment method efficiency.
9 cl, 2 tbl, 41 ex
FIELD: chemistry, pharmacology.
SUBSTANCE: claimed invention relates to compounds of formula (I) or their pharmaceutically acceptable salts, where Q represents optionally substituted with 1-3 substituents, determined in formula, phenyl or pyridyl or pyrodazinyl; R2 represents C1-6alkyl or aminogroup, determined in item 1 of formula or C1-6alkyl, substituted with said aminogroup; bond between oxygen atom O* and adjacent carbon atom C1 or (i) is double bond, which determines carbonyl group [C(=O)], where R6 represents C1-6alkyl or cyclopropyl; or (ii) represents simple bond, where, in case of simple bond, said oxygen atom O*, is in addition bound to group R6 and, taken together with R6 and with adjacent nitrogen atom, determines optionally substituted with C1-6alkyl, oxadiazolyl ring, bond between C1 and adjacent nitrogen atom being double bond.
EFFECT: obtaining medications which are useful in obtaining medications for treatment of conditions connected with p38 kinase and/or in obtaining medications for treatment of inflammatory diseases or conditions in patient.
8 cl, 6 tbl, 88 ex
SUBSTANCE: described are 2,4,6-phenyl-substituted cyclic ketoenols of formula (I, in which W, X, Y and CKE are given in invention formula. Also described are esters of acylamino acids of formula (II), substituted derivatives of phenylacetic acid of formula (XXIX), (XXVII), (XXXI), which are intermediate compounds for obtaining formula (I) compound.
EFFECT: obtaining herbicidal preparation containing combinations of biologically active substances, including (a), formula (I) compound and (b') improving compatibility with cultural plants mefenpyr-diethyl, with weight ratio 5-1:1-7.7.
9 cl, 46 tbl, 36 ex
FIELD: organic chemistry.
SUBSTANCE: invention relates to new ionic liquids designated for using in electrochemical cells and in organic synthesis. Invention describes ionic liquids of the general formula: K+A- (I) wherein K+ represents one of cations of the group consisting of the following formulae: wherein R1-R5 can be similar or different and can be bound to one another by a simple or double bond also, and each of them separately or in common can represent the following values: hydrogen atom (H), halogen atom, (C1-C8)-alkyl radical that can be partially or completely substituted with the following groups but preferably with fluorine atom (F), chlorine atom (Cl), N-[CnF(2n+1-x)Hx]2, O-[CnF(2n+1-x)Hx], SO2-[CnF(2n+1-x)Hx] or CnF(2n+1-x)Hx wherein 1 < n < 6 and 0 < x < 2n+1; A- means anion taken among the group consisting of [PFx(CyF(2y+1-z)Hz)6-x]- wherein 1 ≤ x ≤ 6, 1 ≤ y ≤ 8 and 0 ≤ z ≤ 2y+1. Invention provides the development of ionic liquids showing broad range of liquid state, high thermal resistance and low corrosive activity.
EFFECT: improved and valuable properties of ionic liquids.
SUBSTANCE: invention pertains to a new method of obtaining derivatives of N-phenyl-2-pyrimidineamine (2-anilinopyrimidine) with general formula (I), which have a wide spectrum of biological effects and can be used mainly, for treating various types of tumours, leucaemia, cerebral ischemia, vascular stenosis and other diseases. In general formula (I) , R1 represents a pyridyl or its oxide bonded to a carbon atom, which can be substituted with a low alkyl or alkoxy, each of R2 and R3 independently represents hydrogen, branched of unbranched low alkyl, phenyl, unsubstituted of substituted with a haloid, R4 represents hydrogen, unbranched or branched low alkyl, R5 represents hydrogen, low alkyl, possibly substituted with halogen atoms. Other representations of radical are given in the formula of invention. The method involves the following stages: A) reaction of urea, mainly in a basic medium with N,N-dialkyamino-1-(3-pyridyl)-2-propene-1-ono with general formula II: with obtaining of the corresponding dihydropyrimidinone with general formula (III) B) oxidation of compound (III) by proton oxidation, with obtaining of the corresponding hydroxypyrimidine with formula IV , C) activation of the hydroxy group in the obtained compound IV , for example, treatment using sulphohalide R'SC2Hal or anhydride R'(SO2)2O, with obtaining of a compound with general formula V , where R' represents aryl of low alkyl, D) reaction of the obtained compound V with the corresponding aromatic amino compound with formula VI , with obtaining of compound with formula (I) and subsequent possible conversion of the obtained compounds to other compounds with general formula (I).
EFFECT: method allows for excluding use of toxic compounds and simplifies the process.
13 cl, 13 ex