The way to obtain 2,6-dimethyl-3,5-dichloro-4(1h)-pyridone
(57) Abstract:Usage: for the treatment and prevention of coccidiosis in commercial poultry production. The inventive 2,6-dimethyl-3,5-dichloropyridine-4. Reagent 1: 2,6-dimethyl-4(14)pyridone. Reagent 2: sodium chloride. Reaction conditions: by electrolysis in a membrane electrolyzer on ksirodarnavasambhavam the anode when the anode current density 15-20 A/l, a temperature of 15-20 degrees.C and pH = 9, the concentration of reagent 1 5-20 g/l, and reagent 2 200-300 g/l, measured flow in the anode electrolyte reagents and aqueous solution of NaOH or Na2CO3. table 2., 1 Il. The invention relates to chemical technology for veterinary drug 2,6-dimethyl-3,5-dichloro-4(1H) pyridone (tarmacced) used for treatment and prevention of coccidiosis in commercial poultry production.Known methods of obtaining tarmacced the chlorination of 2,6-dimethyl-4(1H)pyridone gaseous chlorine  or potassium chlorate in the environment of hydrochloric acid  the Disadvantages of these methods are the dangers of using chlorine gas, a deficit of potassium chlorate and expensive technological equipment made of titanium, enameled cast iron.Known bezopasny output of tarmacced to 85% However, a significant drawback of this method is the necessity of neutralization of up to 30 litres of waste water per 1 kg of the finished product without regard to the wash water, what complicates the technology and increases the cost of tarmacced.The aim of the invention is to increase the output of tarmacced and reduce waste production.This goal is achieved by electrochemical chlorination of 2,6-dimethyl-4(1H)pyridone in an aqueous solution at econometricians the anodes (ORT) in membrane electrolysis at a current density of from 0.84 to 2.0 kA/m2, volumetric current density 15-20 A/l, a temperature of 15-25oWith NaCl concentration of 200-300 g/l at pH 2-9, the concentration of 2,6-dimethyl-4(1H)pyridone 5-20 g/l and at a dose in the anode electrolyte saturated aqueous solution of 2,6-dimethyl-4(1H)pyridone. The method allows to obtain tarmacced with access to 87.9% and a small amount of waste (5 l/kg of product, taking into account the wash water). The advantage of this method is the ability to obtain a scarce sodium hydroxide, which is formed in the cathode space of the electrolyzer (2 mol per mol of tarmacced with metering to neutralize accumulated in the anolyte hydrochloric acid).The scheme of the laboratory setup is given on the drawing, where: 1 cell, 2 - capacity anolyte, 3 capacity Catolica, 4 pumps, 5 knock-out box.Methodology elektrolizerami 2,6-dimethyl-4(1H)pyridone output tarmacced presented in table.1. Results ten of electrolysis in the series are presented in table.2.Example 1. In the device 2, provided with a stirrer and a thermometer (see diagram), is filled with 800 ml of an aqueous solution containing 5 g of 2,6-dimethyl-4(1H)pyridone and 200 g NaCl anolyte. In the apparatus 3 is filled with 600 ml of 2% aqueous solution of NaOH catholyte. Included pumps 4 and terminal membrane filtermessage cell 1 is energized, the corresponding amperage 15 A. (Square of ORTA 120 cm2the current density of 1.25 kA/m2, volumetric current density of 18.7 A/l) cold water over the shirt apparatus 2, the temperature of the anolyte is maintained in the range of 15-25oC. during the electrolysis in the apparatus 2 is dosed with 100 ml saturated aqueous solution of 2,6-dimethyl-4(1H)pyridone containing 10 g of the basic substance with a speed that ensures the constancy of its concentration in the anolyte and 10% aqueous NaOH solution to maintain the pH of the anolyte within 2-9 (pH of the solution is controlled by pH-meter).By passing 4 F electricity per mole of 2,6-dimethyl-4(1H)pyridone, dozirovannogo in the form of saturated solution (after 32 minutes after switching on the unit), voltage is removed and the contents of the apparatus 2, which is an aqueous suspension of tarmacced, filtered to orangedental-4(1H)pyridone. Tarmacced on the funnel is washed, and then dried in a drying Cabinet at a temperature of 60-70oC to constant weight.The output of tarmacced 14,44 g (92,6%).Found: C 43,9; H 3,4; 7,4; Cl 37,2% C7H7NOCl2< / BR>Calculated: C 43,7; H 3,6; 7,3; Cl 37,0%
The amount spent anolyte 780-800 Jr. due to electroosmotic migration of water in the catholyte volume of the anolyte during electrolysis is reduced to 700-720 mm. to compensate For the volume of anolyte to the original during electrolysis is added to 80-100 ml of water in a saturated dosing of a solution of 2,6-dimethyl-4(1H)pyridone. In the anolyte is added 20 g of NaCl, and then carried out the following electrolysis. In the subsequent electrolysis of 2,6-dimethyl-4(1H)pyridone is added to the anolyte only in the form of saturated solution for dosing.Total removal of the product from the series (see tab.2) is 142,4 g (91.2 per cent), the total volume of wastewater, including washing, 800 g Specific volume of wastewater is 5.6 l/kg for the series, which is considerably lower than in known methods of obtaining tarmacced.Specific volume of wastewater can be reduced by increasing the number of syntheses on a single electrolyte.Example 2. The method and conditions of the experiment, Asia hydrochloric acid is used 15% aqueous solution of Na2CO3.The output of tarmacced 14,18 g (90,8%).Carrying out electrolysis at a temperature below 15oWith no increases yield, but requires additional energy consumption for cooling, the temperature increases above 25oWith reduces the yield of the target product.In the electrolysis, where the current density is not more than 1 kA/m2used cation-exchange membrane MK-40, in other fluoropolymer membrane MF-SC. Tests at higher current density was not conducted, since 2 kA/m2the limiting current density for a more sustainable membrane MF-SC.The choice of the analyte is determined corrosion resistance ORT, equipment and quality of the product. ORT allows long periods of operation at pH 1,65, in addition, at pH<2 in chloride solutions begins intensive corrosion of stainless steels. Therefore, the experiments at pH<2 were not conducted. At pH>9 the finished product is brown in color and does not meet SPECIFICATIONS. The experiments showed no dependence of the yield of tarmacced from the pH of the anolyte in this range.The choice of anode material ORT is determined by its adaptability, low U  according to which higher outputs chlorinated in electrochemical chlorination observed when using anodes made of this material.Thus, conducting electrolysis under optimal conditions allows to obtain tarmacced with access 87,9-of 92.6% with a minimum amount of liquid waste 5 l/kg of product, plus NaOH 0.6 to 0.8 kg/kg of synthesized tarmacced.The organization of production, this method can form the basis of modern high-performance low-waste technology of obtaining tarmacced. The way to obtain 2,6-dimethyl-3,5-dichloro-4(IN)of the pyridone by chlorination of 2,6-dimethyl-4(IH)pyridone in an aqueous medium, characterized in that carry out the electrolysis in membrane electrolyzer on ksirodarnavasambhavam the anode when the anode current density is 0.84 a 2.0 kA/m2, volumetric current density of 15 to 20 A/l, a temperature of 15 25oWith and while maintaining a pH of 9, the concentration of 2,6-dimethyl-4(IH) pyridone 5 20 g/l and the concentration of sodium chloride 200 to 300 g/l by dosing into the anode electrolyte reagents and aqueous hydroxide solution or sodium carbonate.
SUBSTANCE: there is disclosed compounds of formula II , where each R2 independently stands for H, halogen, cyano, NO2, OR5, NR6R7, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, arylalkyl, substituted arylalkyl, heterocycloalkyl or substituted heterocycloalkyl; B represents O, S, SO or SO2; each W and X independently represents C or N; n is within 0 to 4 if both W and X represent C, 0 to 3, if either X or W represent N, and 0 to 2 if both X and W represent N; R3, R5, R6, R7 are independently chosen from H, alkyl, substituted alkyl, alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo; R4 represents optionally substituted 5-6-merous heteroaryl containing nitrogen atom provided (a) if R4 stands for pyridyl, R4 is not substituted with both hydroxy and methoxy groups; and (b) R4 stands for pyrimidinyl, it is n-substituted =O; A is chosen from following compounds of formula: , where D stands for S or O; m is within 0 to 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 and R27 are independently chosen from H, halogen, NR30R31, OR32, CO2R33, SO2R36, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, -CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R28 and R29 are independently chosen from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl or together they form carbocyclic or heterocyclic ring consisting of 3 to 8 atoms; and R30, R31, R32, R33 and R36 are independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl as pharmaceutical composition for cancer treatment containing compound of formula II.
EFFECT: production of new compounds and based pharmaceutical composition applied for cancer treatment.
18 cl, 147 ex
SUBSTANCE: invention relates to novel compounds of formula , where Qa is phenyl or heteroaryl, and Qa can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; R1 and R2 are each independently selected from hydrogen and (1-6C)alkyl; Qb is phenyl or heteroaryl, and Qb can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl and (1-6C)alkylsulfonyl; where any of the substitutes Qa and Qb defined above, containing a CH2 group which is bonded to 2 carbon atoms, or a CH3 group bonded to a carbon atom, can possibly carry on each of the said CH2 or CH3 group one or more substitutes selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; where heteroaryl is an aromatic 5- or 6-member monocyclic ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulphur, and can be condensed with a benzene ring or a five-member nitrogen-containing ring containing 2 nitrogen atoms; as well as pharmaceutically acceptable salts thereof. The invention also relates to a method of producing formula I compounds, a pharmaceutical composition and use of these compounds for treating conditions mediated by effect of TNF cytokines.
EFFECT: more effective treatment.
13 cl, 3 tbl, 46 ex
SUBSTANCE: invention relates to a compound of formula (II-A) or pharmaceutically acceptable salt thereof: [in which symbols denote the following: R10-R12: are identical or different and each denotes halogen, lower alkyl, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, R13: R0, halogen, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, ring B: benzene ring or a 5-6-member heteroaromatic ring containing 1-2 heteroatoms selected from O, S and N, R14: R0, halogen or -OR0, R0: are identical or different and each denotes H or lower alkyl, Y1: a single bond, lower alkylene, lower alkenylene or O-lower alkylene-, and Z1: -CO2R0 or -C0-NH-SO2-lower alkyl]. The invention also relates to a pharmaceutical composition based on the said compound, having antagonistic effect on the EP1 receptor.
EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in a medicinal agent for treating lower urinary tract symptoms.
6 cl, 56 tbl, 231 ex
SUBSTANCE: compound, represented by formula
or its pharmaceutically acceptable salt, where Y1 represents nitrogen atom or group, represented by CRA, Y2 represents nitrogen atom or group, represented by CRB, Y3 represents nitrogen atom or group, represented by CRC, RA, RB and RC, which can be similar or different, each represents hydrogen atom, etc. (except in the case, when Y1 is CRA, Y2 is CRB and Y3 is CRC), X represents oxygen atom, etc., R1 represents C1-C6alkyl group, etc., R3 represents optionally substituted phenyl group, etc., R4 represents hydrogen atom, etc., and R5 represents optionally substituted phenyl group, etc.), possesses inhibiting action with respect to S1P binding with its receptor Edg-1(SlP1).
EFFECT: obtaining composition, which can be used as therapeutic medication in case of autoimmune diseases, rheumatoid arthritis, asthma, atopic dermatitis, rejection after organ transplantation, cancer, retinopathy, psoriasis, osteoarthritis or age-related macula lutea degeneration, etc.
13 cl, 9 ex, 1 tbl, 4 dwg
SUBSTANCE: invention relates to organic chemistry, namely to derivatives of 4-pyridinone formula I or pharmaceutically acceptable salts thereof, where A is hydrogen, B(OH)2, halogen, C(O)NH(CH2)nC(O)N(R3)2; X is hydrogen or halogen; Y denotes phenyl, benzimidazolil, benztiazolil, benzoksazolil, benzpiperidinil, quinolyl, indolyl, indazolyl or pyridyl, each optionally substituted with 1-3 groups Ra, provided that Y denotes phenyl, then at least one of said Ra selected from OCF3, O(CH2)nC3-6cycloalkyl, NR2C(O)R2, C(O)R2, N(R2)2, (CH2)nC(O)OR2, OR2, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, (CH2)n(C)6-10aryl, O(CH2)nC6-10aryl or O(CH2)nheterocyclyl, where said heterocyclic ring and aryl optionally substituted with 1-3 groups Rb; R1 represents hydrogen, NR2R3, Si(CH3)3, (CH2)nC6-10aryl, C2alkenyl or C1-4alkyl, said alkyl and alkenyl optionally substituted with 1-3 groups of halogen, OH, C1-6alkyl, O-C1-6alkyl, NR2R3, SOR2, NHSO2R2, CF3, C6-10aryl, heterocyclyl, -C≡C-C6-10aryl, C(O)NR2R3, wherein said aryl and heterocyclyl optionally substituted with 1-2 groups Ra; R2 and R3 independently denote H, C1-6alkyl, (CH2)nheterocyclyl, (CH2)nC6-10aryl, wherein said aryl optionally substituted by group Ra or R2 and R3 together with nitrogen atom to which they are bonded, form a 6-member ring, which contains oxygen; Ra is C1-6alkyl, halogen, CF3, OCF3, C3-6cycloalkyl, O(CH2)nC3-6cycloalkyl, NR2C(O)R2, C(O)R2, CN, N(R2)2, (CH2)nC(O)OR2, OR2, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, (CH2)nC6-10aryl, O(CH2)nC6-10aryl or O(CH2)nheterocyclyl, wherein said heterocyclyl and aryl optionally substituted with 1-3 groups Rb; Rb is C1-6alkyl, halogen, CHF2, oxo (=O), N(R2)2, CH2OH, S(O)2NR2R3, (CH2)nC6-10aryl, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, OR2, C3-6cycloalkyl, CF3 or CN; and n equals 0-3; and where heterocycle is aromatic or saturated or partially saturated monocyclic or bicyclic ring containing 5-10 atoms, among which 1-4 atoms are heteroatoms selected from nitrogen, oxygen and sulphur. Invention also relates to pharmaceutical composition based on compound of formula I, method of treating and/or preventing neurological and psychiatric disorders and method of intensifying action of antipsychotic agent based on use of compound of formula I.
EFFECT: new compounds are prepared effective in treating diseases associated with catechol-O-methyltransferase (COMT).
52 cl, 1 tbl, 17 ex