The method of obtaining morpholine 3-methyl-1,2,4-triazolyl-5 - thioacetate showing hepatoprotective, wound healing and antiviral activity

 

(57) Abstract:

The method of obtaining morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate showing hepatoprotective, wound healing and antiviral activity, involves mixing 3-methyl-1,2,4-triazoline-5-thione with morpholine, heating the reaction mixture in the medium of organic solvent and isolation of the target product in the form of crystalline powder. In addition, the reaction mixture was further added alkali metal CHLOROACETATE. The alkali metal CHLOROACETATE and morpholine are mixed in a molar ratio of 1:1:(1,0-1,1), respectively. The method provides a higher purity, activity and output of the target product. table 1.

The invention relates to the production technology of heterocyclic substances, in particular to the production technology, morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate used in medicine and veterinary.

The closest in technical essence and the achieved technical result of the claimed is a method for morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate showing hepatoprotective, wound healing and antiviral activity, as outlined in the patent of Ukraine N 1988 from 22.12.86, publ. 20.12.94, M. Close in the medium of organic solvent and isolation of the product in the form of crystalline powder.

As tizamidine 3-methyl-1,2,4-triazole using 3-methyl-1,2,4-triazolyl-5-thioacetate, which is mixed with morpholine in a molar ratio of 1:1.

Getting morpholine 3-methyl-1,2,4-triazolyl-thioacetate known manner accompanied by contamination of the target product of unreacted 3-methyl-1,2,4-triazolyl - 5-teoksessa acid, due to the volatility of the research, education associates. The use of contaminated drug can cause oral ulceration of the stomach and duodenum due to the fact that 3-methyl-1,2,4-triazolyl-5 - teoksessa acid has ulcerogenic action.

The basis of the invention the task is improving the method of obtaining research 3-methyl-1,2,4-triazolyl-5-thioacetate showing hepatoprotective, wound healing and antiviral activity, in which by using a new set of the initial substances in the new value can be no contamination of the desired product, 3-methyl-1,2,4-triazolyl-5-teoksessa acid and enhances the purity and activity of the target product, but also increases the yield of the target product.

The problem is solved in wound healing and antiviral activity, includes mixing tizamidine 3-methyl-1,2,4-triazole with morpholine, heating the reaction mixture in the medium of organic solvent and isolation of the target product in the form of crystalline powder according to the present invention, what is new is that in the reaction mixture is further added alkali metal CHLOROACETATE, and as the substituted 3-methyl-1,2,4-triazole using 3-methyl-1,2,4-triazoline-5-tion, while 3-methyl-1,2,4-triazoline-5-tion, the alkali metal CHLOROACETATE and morpholine are mixed in a molar ratio of 1:1 (1,0 - 1,1), respectively.

Between its significant distinguishing features of the claimed invention and achievable technical result is the following causal link.

Use as tizamidine 3-methyl-1,2,4-triazole 3-methyl-1,2,4-triazoline-5-thione and additional introduction into the reaction mixture chloracetate alkali metal when the claimed ratio of components in the reaction mixture ensures conditions of the reaction of formation of the target product, precluding the formation of excess 3-methyl-1,2,4-triazolyl-5-teoksessa acid.

Interaction chloracetate alkali metal 3-may acid is formed equivalent with respect to alkaline agent number. Morpholine is an alkaline agent, interacting with the resulting 3-methyl-1,2,4-triazolyl-5-teoksessa acid, forms a target product morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate not contaminated 3-methyl-1,2,4-triazolyl-5-teoksessa acid.

Education morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate from the claimed source of the substance is the reaction

< / BR>
where M is alkali metal (Na, K, Li).

The claimed ratio of the components in the reaction mixture is established experimentally, and provides the maximum yield of the target product is not contaminated with impurities, by-products of the reaction.

The method is as follows.

The declared amount of 3-methyl-1,2,4-triazoline-5-thione is mixed with the claimed number of chloracetate alkali metal, the mixture is dissolved in ethanol by heating to boiling. To the solution was added the claimed amount of research, continuing to boil for 20-30 minutes. Then a hot solution is filtered, removing the precipitated precipitated chloride of an alkali metal. The filtered solution is cooled to a temperature of 10oC, the precipitation is filtered and dried, obtaining the target product morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate.

The inventive method was tested in laboratory conditions.

As starting substances for the implementation of the method used: 3-methyl-1,2,4-triazoline-5-tion (TU 6-09-12-2227-86); morpholine (TU 609-649-76); ethanol; CHLOROACETATE sodium; potassium CHLOROACETATE; lithium CHLOROACETATE.

In dvuhgolosy flask equipped with a mechanical stirrer and reflux condenser, was placed to 116.2 g (1 mol) of 3-methyl-1,2,4-triazoline-5-thione, 117,5 g (1 mol) of chloracetate sodium and 440 ml of ethanol. The mixture was heated to boiling and added 78,4 - of 104.5 g (0,9 - 1,2 mol) of the research. Boil 20 to 30 minutes and filtered while hot to separate the precipitated precipitated sodium chloride. The filtered solution was cooled to 10oC, the precipitation was filtered and dried, obtaining the target product morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate in the form of white crystalline powder. In the experiments was controlled by the following indicators: yield of the target product (in % of theoretically possible was determined by weighing on scales Mora, followed by calculation); the number of impurities (in %).

The presence of impurities 3-methyl-1,2,4-triazolyl-5-thioacetate controlled chromatographic method in a thin layer of sorbent on the plates "Silufol" in the solvent system ethanol-hecaitou shown in the table. In experiments NN 2-4 source materials were mixed in the claimed ratio, as in experiments 1, 5 - in ratios outside the claimed range.

We also conducted experiments using as chloracetate alkali metal CHLOROACETATE potassium and chloracetate lithium. The results of these experiments (the yield of the target product and the amount of impurities in it) is similar to the examples presented in the table for chloracetate sodium, because the table is not shown.

Was also conducted an experiment to obtain morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate method prototype (see experience N 6).

The table shows that the best results are obtained when the claimed ratio of components in the reaction mixture (see NN experiments 2-4): maximum yield of the desired product (98%) with a minimum content of impurities (0,0-0,5%), which provides high activity of the target product.

The reduction of the research claimed below leads to a decrease of the yield of the target product and the increase in the content of impurities in it (see experience N 1).

The increase in the number of research higher claimed impractical, because does not improve the yield of the target product (see experience N 5).

Compared to acetate with a minimum content of impurities, this ensures a high yield of the target product.

The method of obtaining morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate showing hepatoprotective, wound healing and antiviral activity comprising mixing tizamidine 3-methyl-1,2,4-triazole with morpholine, heating the reaction mixture in the medium of organic solvent and isolation of the target product in the form of a crystalline powder, characterized in that the reaction mixture is further added alkali metal CHLOROACETATE, and as tizamidine 3-methyl-1,2,4-triazole using 3-methyl-1,2,4-triazoline-5-tion, while 3-methyl-1,2,4-triazoline-5-tion, the alkali metal CHLOROACETATE and morpholine are mixed in a molar ratio of 1:1:(1,0 - 1,1), respectively.

 

Same patents:

The invention relates to an improved method of obtaining a known regulator of growth - meekatharra, N,N-dimethylpiperidinium

The invention relates to medicine, specifically to medicines used in the treatment of ischemic heart disease, and arrhythmias complicating it

The invention relates to new derivatives thiocarbonic acid having biological activity, in particular to substituted aromatic Amida thiocarbonic acid and the herbicide agent containing them

The invention relates to substituted derivative asalaam, which is an effective anti-Helicobacter tools that can be used as monotherapy for eradication of Helicobacter pylori and related species

The invention relates to cyclic Amida substituted in-the position of different aryl groups, agricultural suitable salts and their mixtures, and their use as fungicides systemic or selective action

The invention relates to new chemical compounds having valuable properties, in particular to new derivatives of sulfonamidophenylhydrazine

The invention relates to the production of 1-arestriction formula I, where R is lower alkyl; X is halogen, lower alkyl, nitro, hydroxy, -NHSO2R', -Ni(SO2R')2, -N(R')SO2R'; R' is lower alkyl; n is an integer from 0 to 3, processing of arestriction formula II halogenoacetyl acid or its salt in the environment tert-butanol - water at a weight ratio of (95-70):(5-30), respectively

The invention relates to the field of synthesis of heterocyclic compounds

The invention relates to organic chemistry, specifically to diacrylate derived triazolone formula I

< / BR>
which can be used as a modifier acrylic photopolymerizable compositions and creation on their basis of protective and strengthening coatings of optical fibers

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention relates to new substituted benzoylketones of the general formula (I): , all possible tautomeric forms and possible salts that can represent active substance as a component of herbicide agent. In the formula (I) A means (C1-C4)-alkyl; R1 means cyclo-(C3-C6)-alkyl; R2 means hydrogen atom (H), cyano-group (CN); R3 means hydrogen atom (H), halogen atom, CF3, (C1-C4)-alkylsulfonyl; R4 means halogen atom; X means groups: or wherein R5 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkylthio-group, di-(C1-C6-alkyl)-amino-group; R6 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, cyclo-(C3-C6)-alkyl; n = 0 or 1 including all possible tautomeric forms and possible salts. Compounds of the formula (I) elicit herbicide activity and can be used in herbicide composition.

EFFECT: valuable properties of compounds.

3 cl, 1 sch, 3 tbl, 13 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes substituted benzoylcyclohexanediones of the general formula (I):

wherein m = 0 or 1; n = 0 or 1; A means a single bond or alkanediyl (alkylene) with 1-4 carbon atoms; R1 means hydrogen atom or unsubstituted alkyl with from 1 to 6 carbon atoms; R2 means methyl; R3 means hydrogen atom, nitro-, cyano-group, halogen atom, alkyl with from 1 to 4 carbon atoms substituted with halogen atom, alkoxy-group with from 1 to 4 carbon atoms or alkyl sulfonyl with from 1 to 4 carbon atoms; R4 means nitro-group, halogen atom, unsubstituted alkyl with from 1 to 4 carbon atoms of that substituted with halogen atom; Z means heterocycle, and herbicide agent based on thereof. Also, invention describes substituted derivatives of benzoic acid of the general formula (III):

wherein values n, A, R3, R4 and Z are given above. These compounds represent the parent substances used for preparing compound of the formula (I). Compounds of the formula (I) elicit high and selective herbicide activity.

EFFECT: valuable properties of compounds.

7 cl, 8 tbl, 7 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: substituted benzoylisoxazols of general formula I are described, wherein R1 is cycloalkyl; R2 is hydrogen, alkoxycarbonyl; R3 is halogen, substituted alkyl, alkoxyl; R4 is halogen, alkoxil; Z is substituted 5-membered saturated or unsaturated heterocycle having 1-3 nitrogen atoms and additionally including one oxogroup (C=O). Also disclosed is herbicidal agents, containing compounds of formula I.

EFFECT: effective suppression of weeds in such cultures as maize and wheat.

16 cl, 6 tbl, 4 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to novel retinoid compounds of the structural formula (I) or their pharmaceutically acceptable salts and pharmaceutical compositions possessing agonistic activity with respect to retinoid receptors and comprising indicated compounds wherein n = 1; d = 0 or 1; B means -CR7=CR8-, -CH2O- wherein R7 and R8 each means independently hydrogen atom; X means phenyl optionally substituted with halogen atom, or 5-membered heteroaryl comprising sulfur atom (S) as a heteroatom; R1 means -C(=O)-R9 wherein R9 means alkyl, hydroxyl, amino-, heteroaryloxy-group comprising oxygen atom (O) or 6-membered heterocyclyl comprising nitrogen atom (N) as a heteroatom; R2 means: (a) -(CR10R11)m-Yp-R12; m means a whole number from 1 to 10; p means 0 or 1; R10 and R11 mean hydrogen atom; Y means -O-, -S- or -NR13-; R13 means hydrogen atom; R12 means hydrogen atom, alkyl, cycloalkyl, phenyl, 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom, 5- or 6-membered heteroarylalkyl comprising atoms N, S, O as a heteroatom, heteroalkyl comprising atoms N, S, O as a heteroatom, 5- or 6-membered heterocyclyl comprising atoms N, S, O as a heteroatom, or 5- or 6-membered heterocyclylalkyl comprising atoms N, S, O as a heteroatom under condition that when p means 0 then R12 doesn't mean hydrogen atom or alkyl; (b) 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom; (c) -Z-L wherein Z means -CR14=CR15-, -C≡C-, -C(=O) or -S-; R14 and R15 mean hydrogen atom; L means 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom; (d) -CR14=CR15-L1 wherein L1 means -S(O)2R17 or -SO2NR18R19 wherein R17 means alkyl; R18 and R19 mean hydrogen atom; each R3 means independently hydrogen atom, hydroxyl or oxo-group; t means 1 or 2.

EFFECT: valuable medicinal properties of compounds and compositions.

59 cl, 10 tbl, 54 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 1,2,4-triazolone-3- representing the parent component used in the creature of energy-saturated materials - gun powders, fuels, explosive substances, blowing agents. Method involves interaction of acetone semicarbazone with formic acid in the presence of 96% sulfuric acid as the reaction activating agent in the mole ratio of reagents = 1:(4.5-5.5):(0.35-0.45), respectively, at temperature 107-110°C for 12 h. Method provides simplifying the process and to enhance the yield of the end product.

EFFECT: improved method of synthesis.

1 tbl, 1 ex

FIELD: herbicides, agriculture.

SUBSTANCE: herbicide composition is prepared as emulsion concentrate that is characterized by the presence of carfetrazon-ethyl, 2,4-D 2-ethylhexyl ester and organic solvent in the following content of components per 1 l of solvent: carfetrazon-ethyl, 2-50 g/l; 2,4-dichlorophenoxyacetic acid (2,4-D) 2-ethylhexyl ester, 400-700 g/l. Xylene is used as an organic solvent. For control of weeds the above said composition is taken in the dose 0.5-0.6 l/ha that is diluted and cereal crops are sprayed in bushing out phase and maize - in phase of 3-5 leaves. Invention provides decreasing consumption dose of herbicides.

EFFECT: valuable properties of herbicide.

2 cl, 2 tbl

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention relates to novel substituted arylketones of the general formula (I): wherein n = 1; A means alkanediyl (alkylene) comprising from 1 to 6 carbon atoms; R1 means one of the following groups: ; R6 means -OH; R7 means hydrogen atom (H); R8 means H, (C1-C6)-alkyl substituted if necessary with (C1-C6)-alkoxyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group; R9 means -OH; R2 means H, halogen atom, (C1-C4)-alkylsulfonyl group, (C1-C6)-alkyl substituted if necessary with halogen atom; R3 means halogen atom, (C1-C4)-alkylthio-group, (C1-C4)-alkylsulfonyl; R4 means one of the following heterocyclic groups: wherein a dotted bond represents a simple bond of double bond; Q means oxygen atom; R14 means H, (C1-C6)-alkyl substituted if necessary with (C1-C4)-alkoxyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group or (C3-C6)-cycloalkyl; R15 means H, (C1-C6)-alkyl substituted if necessary with (C1-C4)-alkoxyl, (C1-C6)-alkoxy- (C1-C6)-alkylthio-group and wherein separate radicals R14 and R15 bound by similar heterocyclic groups can be similar or different within the limits of above given definition and involving all possible tautomeric forms of compounds of the general formula (I) and possible salts or adducts of acids and bases of the general formula (I). Compounds of the formula (I) can be used as herbicide agent.

EFFECT: valuable property of compounds.

5 cl, 8 tbl, 14 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to fluoroalkoxyphenylsulphonylamino(thio)carbonyl triazolynes of general formula I wherein n = 2 or 3; Q1 is sulfur or oxygen; Q2 is oxygen; R1 is methyl, optionally substituted with fluorine, C2-C4-alkyl, C1-C4-alkoxy; R2 is F, Cl, Br, methyl, optionally substituted with methoxy, C2-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, di-C1-C2-flkylamino, C3-C6-cycloalkyl, C3-C6-cycloalkylmethoxy; R3 is C1-C3-alkyl, C1-C3-alcoxy, C3-C6-cycloalkyl, except for certain compounds wherein n = 2; R1 is methyl; Q1 is oxygen; R2 is C1-C3-alkoxy or methyl; R3 is methyl or cyclopropyl, or salts thereof and herbicidal agent based on the same.

EFFECT: compounds with good compatibility with cultural plants and improved herbicidal activity.

5 cl, 3 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: novel compounds of formulas , , , , , , (designation of all groups are given in invention formula) are used for treatment of different metabolic diseases, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver, cachexia, obesity, atherosclerosis and arteriosclerosis.

EFFECT: using compounds as biologically active agent and creating pharmaceutical compositions based on said compounds.

124 cl, 52 ex, 17 tbl, 2 dwg

Up!