5-alkoxy [1,2,4]triazolo[1,5-c]pyrimidine-2(3h)-tinavie compounds, 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c] pyrimidine), a way of producing 2,2'-dithiobis(5-alkoxy[1,2,4] triazolo[1,5-c]pyrimidine and 2-chlorosulfonyl-5-alkoxy[1,2, 4]triazolo[1,5-c]pyrimidine compounds

 

(57) Abstract:

The invention relates to new compounds, which can be a potent herbicide. Describes 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-(3H)-tinavie the compounds of formula I where one of Y and Z represents F, Cl, Br, and the other represents H; and R represents a CH3or C2H5. Describes two ways to obtain 2-chlorosulfonyl-5-alkoxy[1,2,4]-triazolo[1,5-c] pyrimidine, and the way to obtain 2,2-dithiobis(5-alkoxy)[1,2,4] -triazolo[1,5-c] pyrimidine, which allow to obtain the compounds with higher yields and purity. 5 C. and 18 h.p. f-crystals.

The present invention relates to 5-alkoxy[1,2,4]-triazolo[1,5-c]pyrimidine-2(3H)-tihonovym compounds and to a method of using these compounds to obtain 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c]pyridine)'REE and 2-chlorosulfonyl-5-alkoxy[1,2,4] triazolo[1,5-C] pyrimidine compounds. In addition, the present invention relates to 2,2'-dithiobis(5-alkoxy[1,2,4] triazolo[1,5-c]pyrimidine)'new compounds and to the use of these compounds to obtain 2-chlorosulfonyl-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine compounds.

5-Alkoxy[1,2,4] triazolo[1,5-c] pyrimid the 5 163 995. As described in this patent, the above compound can be obtained by a multi-stage method, which includes receiving 2-chlorosulfonyl-5-alkoxy[1,2,4] triazolo[1,5-c] pyrimidine intermediates by oxychlorination process corresponding 2-(benzylthio or C2-C4-alkylthio)-5-alkoxy[1,2,4] triazolo[1,5-c] pyrimidine compounds using chlorine in the water environment, and subsequent condensation of these intermediate compounds with a substituted aniline or N-trialkylaluminium connections. Outputs target herbicide products often vary, which is mainly due to the low yields obtained by oxychloination, and impurities present in the resulting 2-chlorosulfonyl-5-alkoxy[1,2,4]-triazolo[1,5-c]pyrimidine intermediate compounds. In addition, this method produces large amounts of waste.

Therefore, it would be extremely important to get more sophisticated methods of obtaining 2-chlorosulfonyl-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine intermediates required for producing a 5-alkoxy[1,2,4]triazolo[1,5-c] pyrimidine-2-sulfonamidnuyu compounds, for example, such methods, which would allow to obtain the connection breakax[1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-tinavie and compounds 2,2'-dithiobis(5-alkoxy[1,2,4] triazolo[1,5-c] pyrimidine)'have not been described in the literature.

In this work were obtained 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-tinavie connection, which, as shown, can be used to produce 2-chlorosulfonyl-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine compounds, either directly or through intermediate 2,2'-dithiobis(5-alkoxy[1,2,4] triazolo[1,5-c] pyrimidine)'new connections; and which thereby can be used to produce 5-alkoxy[1,2,4] triazolo[1.5-c] pyrimidine-2-sulfonamidnuyu herbicides. It was also found that the method of using these compounds is that the 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-tinavie connection is subjected to oxidation with an oxidizing agent, resulting in a gain of 2.2'-dithiobis(5-alkoxy[1,2,4] triazolo[1,5-c] pyrimidine)'new connection, which in turn is subjected to oxychloination obtaining 2-chlorosulfonyl-5-alkoxy[1,2,4]triazolo[1.5-c]pyrimidine compounds. Describes how to obtain the N-(substituted phenyl)-5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamidnuyu herbicides is more simple and economical than the method described earlier.

The present invention relates to 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-tihonovym compound of formula I:3or C2H5.

Preferred compounds of the formula I are primarily of compounds in which one of Y and Z represents F, Cl or Br, and the other represents H. Usually preferred are fluorinated compounds; however, sometimes more preferable can be chlorinated compounds.

The present invention also relates to a method of using 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-Tihonovich compounds of formula I:

< / BR>
where one of Y and Z represents F, Cl, Br, and the other represents H; and

R represents a CH3or C2H5;

while this method differs in that the compound is treated with at least one equivalent of the appropriate oxidizing agent in an inert reaction medium, resulting in a gain of the intermediate compound, namely 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine) formula II:

< / BR>
where R, Y, and Z are defined above; and then, the resulting intermediate compound is treated with at least 5 moles of chlorine in the appropriate aqueous medium suitable for conducting oxychlorination process, resulting in a gain 2-chlorosulfonyl-5-[1,2,4]triazolo[1,5-c]primatene refers to the intermediate 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine)-compounds of formula II:

< / BR>
where one of Y and Z is F, Cl, Br, and the other is H; and R represents a CH3or C2H5.

Mostly preferred compounds of formula II are compounds in which one of Y and Z is F, Cl or Br and the other is H. Compounds in which one of Y and Z is F, and the other is H, is usually preferred, but sometimes a more preferred may be compounds in which one of Y and Z is Cl and the other is H. most Often preferred compounds of formula II are compounds in which R represents ethyl.

5-Alkoxy[1,2,4] triazolo[1,5-c] pyridylimino-2(3H)-tinavie compounds of the present invention can be characterized as compounds in which the alkoxy group is methoxy or ethoxy-group, and which, in 7 - or 8-position has one halogen, alkyl or alkoxylation. These compounds can be represented by formula I:

< / BR>
where R represents methyl or ethyl, and one of Y and Z represents fluorine, chlorine, bromine, and the other represents hydrogen.

Fluorinated compounds are usually preferred, however, are sometimes preferred chlorinated compounds.-2(3H)-tion; 5-methoxy-8-(fluorine or chlorine)-[1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-tion; 5-methoxy-8-(fluorine or chlorine), [1,2,4] triazolo[1,5-c]pyrimidine-2(3H)-tion.

In this application the compounds of formula I are indicated and described as 2(3H)-tinavie connection. With the same success they can be called 2-thiol compounds, as both of these structures are isomers keto - and ealovega type and are in dynamic equilibrium. Below shows keto - and enologia isomers of compounds of formula I:

< / BR>
5-Alkoxy[1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-tinavie the compounds of formula I are not very stable and tend to decomposition during storage even in the solid state. Therefore, these compounds immediately after receiving them, it is preferable to use as intermediates for the synthesis of other more stable compounds.

The compounds of formula I can be obtained by a reaction between 5-alkoxy-1,2,4-triazolo[4,3-C] pyrimidine-3(2H)- tinawag the compounds of formula IV:

< / BR>
(where R represents methyl or ethyl, and one of Y and Z represents fluorine, chlorine, bromine, and the other represents hydrogen, at least one molar equivalent of methoxide or ethoxide alkali metal is full metal and the alcohol must be chosen so that to 5-alkoxy-group of compounds of formula IV, the alkali metal alkoxide and the alcohol had the same alkyl group (methyl or ethyl). If these reagents do not have a match, then you can place exchange reactions, which significantly reduce the outputs and complicate the procedure of the selection.

The alkoxides of alkali metals, which can be used in this reaction are lithium, sodium and potassium derivatives of methanol and ethanol. This reaction is used, at least one molar equivalent of alkali metal alkoxide. Relations alkoxide of an alkali metal to the compound of the formula IV are mostly from 1 to 2. Usually are preferred relationship is equal to 1.03 to 1.3. Higher concentrations of alkali metal alkoxide adversely affect the reaction.

The reaction medium used in the present reaction, must contain the corresponding alcohol, and may also contain other suitable solvents. These solvents should be mixed with the alcohol, should not cause excessive deposition of alkali metal alkoxide, and should not react with any reagent or ethylsulfate etc. While it is preferable that this reaction medium contains less than 2% water. And more preferably, the water content was less than 0.2%, as the presence of water can stimulate adverse reactions that adversely affect the source material, product, or both.

The isomerization process is best proceeds at room temperature, and usually at temperatures from -10oC to 40oC. In most cases, preferred are temperatures from 0oC to 30oC. At higher temperatures the raw materials and products have a tendency to decomposition. This reaction can be carried out usually used for this purpose vessels. When this reaction mixture is thoroughly stirred.

The rearrangement reaction proceeds during the period of from several minutes to several hours, and therefore you get the solution containing salt of an alkali metal and compounds of formula I. thus it is preferable that this solution does not remain for a long period of time, as these salts of the target compounds of formula I are not absolutely stable. Themselves the compounds of formula I can be obtained by way of the at any organic or inorganic arenosa acid. This inexpensive and readily available acid having a pKa less than 8, is hydrochloric acid, sulfuric acid or acetic acid. While preferred is hydrochloric acid. Usually reliable neutralization is necessary to add an excessive amount of acid than is necessary for accurate neutralization.

The target compound of the formula I can be isolated by collecting the precipitate formed after acidification. Water is usually added after acidification and before collecting the precipitate to ensure complete precipitation. The isolated product can be collected by filtration or centrifugation and dried, if necessary, by standard methods, however, should avoid exposure to excessive heat. These compounds can be purified by standard methods such as recrystallization, liquid chromatography, etc.

5-Alkoxy-1,2,4-triazolo[4,3-C]pyrimidine-3(2H)-tinavie the compounds of formula IV can be obtained by a reaction between 2-alkoxy-4-hydrazinopyridazine the compounds of formula V:

< / BR>
(where R represents methyl or ethyl, and one of Y and Z represents fluorine, chlorine, bromine, methyl, ethyl, methoxy or ethoxy and Tuwim compound of formula VI:

< / BR>
where each of R1, R2and R3independently represents a C1-C4-alkyl or benzyl: any two of R1, R2m R3taken together, represent a group of formula : -(CH2)4-, -(CH2)5or O(C2H4)2CH3(C2H4-)2; or all three R1, R2and R3taken together, represent a group of formula N(C2H4-)3. For this reaction the reactants are mixed in an appropriate inert liquid medium, such as aqueous acetonitrile, at temperatures from 0oC to 40oC, and then add at least one mol of hydrogen peroxide at a temperature of from 0oC to 40oC. In this case, as a rule, the mixture was thoroughly stirred. The result of this reaction, which proceeds quite rapidly, formed the target 5-alkoxy-1,2,4-triazolo[4,3 - C] pyridine-3(2H)-tinove compound of formula IV, or if you add trialkylamine connection is formed dialkylammonium salt of the compounds of formula IV. If you get dialkylammonium salt, this salt can be converted into a compound of formula IV by adding at least one mole of a strong acid. the, followed by collecting the resulting precipitate by filtration or centrifugation. Elemental sulfur as a by-product may be removed by standard methods. In this case, usually uses the difference in solubility of sulfur and compounds of formula IV in aqueous bases (compound of formula IV is dissolved, and sulfur is not soluble) and carbon disulfide (Vice versa).

2-Alkoxy-5-substituted-4-hydrazinopyridazine starting materials of formula V can be obtained by treating 2,4-dialkoxy-5-substituted-pyrimidine compounds with hydrazine and triethylamine. Similarly, 2-alkoxy-6-substituted-4-hydrazinopyridazine compounds can be obtained by treating the corresponding 2-alkoxy-4-halogeno-6-substituted-pyrimidine compounds with hydrazine and triethylamine. These reactions are best carried out in water or in a solvent such as acetonitrile, at temperatures from 0oC to 40oC, using one mole of triethylamine and a little more of one mole of hydrazine. Target 2-alkoxy-(5 or 6)-substituted-4-hydrazinopyridazine the compounds of formula V can be isolated by precipitation by addition of water, followed by separation of the precipitate by filtration, centrifuge the data connection without isolation and/or purification.

The way to use 5-alkoxy[1,2,4]triazolo[1,5-C]-pyrimidine-2(3H)-Tihonovich compounds of the formula I is a more effective method of obtaining 2-chlorosulfonyl-5-alkoxy[1,2,4]triazolo[1,5-C]pyrimidine compounds of formula III

< / BR>
where R represents methyl or ethyl, and one of Y and Z represents fluorine, chlorine, bromine, and the other represents hydrogen.

The compounds of formula III can be represented as [1,2,4]triazolo [1,5-c] pyrimidine compounds having chlorosulfonyl group in the 2-position, methoxy - or ethoxy in the 5-position and is halogen, alkyl, or alkoxy-substituent in the 7 - or 8-position. Generally preferred are compounds in which one of Y and Z represents fluorine, chlorine, or bromine, and the other represents hydrogen. More preferred are compounds in which one of Y and Z is a fluorescent and the other represents hydrogen; however, in some cases, more preferred may be compounds in which one of Y and Z represents chlorine, and the other represents H.

Specific compounds which can be obtained in the described manner, are 2-chlorosulfonyl-8-fluorescent-5-methoxy[1,2,4]three is XI[1,2,4] triazolo[1,5-C] pyrimidine; and 2-chlorosulfonyl-7-chloro-5-ethoxy[1,2,4]triazolo[1,5-C]pyrimidine.

The compounds of formula III are known compounds which are described in U.S. patents 5163995 and 5177206 (relevant portions of these patents are introduced in the present description by reference), and which can be used to produce 5-alkoxy[1,2,4]triazolo[1,5-C]pyrimidine-2-sulfonamidnuyu herbicides. For this purpose the compounds of formula I is subjected to the reaction of interaction with an appropriately substituted aniline or N-trialkylaluminium compound in an inert solution such as acetonitrile, in the presence of tertiary amine and/or a catalytic amount of dimethyl sulfoxide.

In the method of using compounds of formula I provides for the implementation of the two-stage procedure that involves the oxidation reaction and the reaction of the oxychlorination process. The first stage of the above procedure is carried out by treatment of 5-alkoxy[1,2,4]triazolo[1,5-C]pyrimidine-2(3H)-tinawag the compounds of formula I;

< / BR>
(where R represents methyl or ethyl, and one of Y and Z represents fluorine, chlorine, bromine, and the other represents a hydrogen in an appropriate oxidizing agent. To this end, compound of formula I, at least the n equivalent of hydrogen peroxide is 0.5 mol. As a result of the reaction, which proceeds very quickly, produces compound 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-C]pyrimidine of formula II

< / BR>
where R, Y, and Z are defined above. The compound of formula II is usually precipitates from the reaction medium and preferably emit in the form of a solid substance.

A suitable oxidizing agent is a compound capable of oxidizing organic thiol and tinavie connection with the formation of disulfides. Such oxidizing agents are hydrogen peroxide; halogen, for example bromine; percolate, such as peracetic acid; diazepamonline, such as acetylmuramic; and alkylperoxide, for example t-butylperoxide. The preferred oxidant is hydrogen peroxide.

In most cases it is preferable to use hydrogen peroxide in the form of a 30% solution in water, which is commercially available. But can also be used and other forms of hydrogen peroxide.

In the described first stage of the process an inert reaction environment is an environment in which both the source material of formula I and intermediate compound of the formula I are moderately stable; in which the source material and oxidizing AG is not catalyze its decomposition under reaction conditions. Usually, this reaction medium as one of its ingredients contains water. Typically, this environment is a mixture of water with methanol, ethanol, 2-propanol, acetonitrile, 1-methoxy-2-propanol, 1,2-dimethoxyethane or tetrahydrofuran. While preferred are water, methanol and ethanol. Preferably also, if the environment is neutral or slightly acidic. When using acidified environment, in this case usually applies hydrochloric acid.

In the described first stage of the process the reaction readily proceeds at room temperature. Basically, the reaction temperature may range from -10 to 80oC; however, the preferred temperature is from 0 to 40oC. This reaction is exothermic, and therefore the reaction, the reaction mixture is preferably cooled. In addition, the reaction mixture is preferably removed, and the oxidizing agent is preferably added slowly or in ever-increasing numbers.

The compounds of formula II obtained in the first stage of this process, basically do not dissolve in the reaction mixture and after their formation are deposited. To ensure complete precipitation morewidely from the reaction medium by filtration or centrifugation. Then, if necessary, the obtained compound can be dried by standard methods and purified by standard methods, such as recrystallization and extraction.

The second stage of this process involves the use of compounds of formula II, obtained as described above, or in any other way. In this stage, the compound of formula II is treated with at least 5 moles of chlorine in the reaction medium and conditions suitable for conducting oxychlorination process of obtaining the compounds of formula III. The compound of the formula III are usually isolated or in the form of a solution in a water-immiscible organic solvent or in the form of solids.

In the second stage of this method, the reaction medium is a medium in which the compound of formula II is at least partially soluble; and in which the compound of formula III is moderately stable. In most cases, it is preferable reaction medium which contains water and an organic solvent and in which, at least partially dissolve the compounds of formula II and formula III. This is preferred if the organic solvent is not smesyweabanty hydrocarbon solvents, for example dichloromethane, chloroform, 1,2-dichloroethane, and perchloroethylene or hydrocarbon solvents such as toluene. In these environments, often as a water source is used an aqueous solution of an acid, for example aqueous hydrochloric acid solution. Mostly preferred are a mixture of water and dichloromethane or chloroform. Other suitable environments are acetonitrile, acetic acid, and formic acid, each of which may be anhydrous or mixed with water. Can also be used aqueous hydrochloric acid with a normality of above 1 to N. for example 6,25 N. hydrochloric acid. As a side product in the reaction oxychlorination process is formed, and then there is always the chloride, and the reaction, its concentration increases. Usually one part of the compounds of formula II used from 3 to 20 hours (by weight) of the reaction medium.

The reaction conditions suitable for conducting oxychlorination process, are the conditions under which the reaction proceeds at a moderate speed, and which do not contribute to the formation of by-products. Usually, the reaction proceeds at a temperature in the range from -20 to 40oC, preferably from the Oia chlorine in the mixture or on top of the mixture, containing the compounds of formula II in an appropriate reaction medium, while stirring and maintaining the desired temperature. Adding chlorine is carried out at a speed conducive to the rapid dispersion, the reaction temperature is continuously controlled.

The compounds of formula II are first obtained either in the form of a solution in an organic reaction medium, either in the form of insoluble solids. If these connections get in the form of a solution, they can be separated by phase separation followed, but an optional washing the organic phase with water or aqueous acid solution. The organic solvent can then be removed by evaporation or distillation under reduced pressure or, if necessary, using other methods. Alternative the resulting solution can be dried by azeotropic distillation by the use of hygroscopic salts or other standard methods, and the product is used in the form of a dry solution. If the compounds of formula III obtained as insoluble solids, they can be isolated by standard methods, for example by filtration or centrifugation and dried Proc. of the th formula IV or of the compounds of formula V without purification of the intermediate compounds of formula I. Thus, the compounds of formula I, the use of which is one of the variants of the present invention, can be obtained from compounds of formula IV described above and used for the production of compounds of formula II without separation from the reaction medium. In addition, the compounds of formula I can be obtained from compounds of formula IV, described above, which in turn can be obtained from compounds of formula V, described above, and used to obtain the compounds of formula II without isolating the compounds of formula IV or a compound of formula I from the reaction medium.

In another embodiment, the present invention relates to a method of using compounds of formula I to obtain a new 2,2'-dithiobis(5-alkoxy[1,24]triazolo[1,5-C]pyrimidine)new compounds of the formula II

< / BR>
where R represents methyl or ethyl and one of Y and Z represents chlorine, bromine, fluorine, and the other represents hydrogen. Obtaining these compounds described above for the first stage in the method of using the compounds of formula I for the production of compounds of formula III.

Consider the method of the present invention provides for the intermediate 2,2-dithiobis (5-alcox one of Y and Z represents fluorine, chlorine, bromine, and the other represents hydrogen. The compounds of formula II can be represented as a symmetric disulfide compounds containing [1,2,4] triazolo[1,5-C] pyrimidine-2-ilen part associated with each sulfur atom; and each of these parts has a methoxy - or ethoxy-substituent in the 5-position, and one halogen, alkyl or alkoxy substituent in the 7 - or 8-position. These compounds are white or whitish crystalline solid.

While the preferred compounds of formula II are compounds in which one of Y and Z represents a fluorine, chlorine or bromine, and the other represents hydrogen. More preferable are compounds in which one of Y and Z represents a fluorine, and the other represents hydrogen; however, sometimes more preferred may be compounds in which one of Y and Z represents chlorine, and the other represents hydrogen. In some cases, it may also be preferred such compounds of formula II in which R represents ethyl.

Preferred compounds of formula II are: 2,2'-dithiobis(8-fluorescent-5-methoxy[1,2,4] triazolo[1,5-C]pyrimidine); 2,2'-dice'-dithiobis(7-chloro-5-ethoxy[1,2,4] triazolo[1,5-C]pyrimidine).

In addition, the present invention relates to the use of compounds of formula II to obtain the compounds of formula III. This method of use may be effected as described above in accordance with the second stage of the complete method of transformation of compounds of formula I to compound of formula III. This method is especially effective when using compounds of formula II in which R represents ethyl. Basically it is preferable to use the compounds of formula II in which one of Y and Z is fluorine and the other is hydrogen, or one of Y and Z is chlorine and the other is hydrogen.

The compounds of formula III can be obtained from compounds of the formula I without obtaining the compounds of formula II as intermediate compounds in a separate reaction stage. This method, involving the use of compounds of the formula I, is carried out by treatment of compounds of formula I, at least 3 moles of chlorine in the reaction conditions conducive to the completion of the reaction oxychlorination process. Suitable for oxychlorination process conditions are the conditions under which this reaction proceeds with the desired reaction rate, and which do not contribute to the formation of by-products. the but from -10oC to 30oC, and more preferably from 0oC to 15oC. Usually the reaction is carried out by ozonation of chlorine in the mixture or on top of the mixture containing the compounds of formula I, in an appropriate reaction medium, while stirring and cooling this mixture to maintain the desired temperature. Chlorine is added so that it was quickly dispergirovanija and that the reaction temperature is well controlled.

Examples

1. Getting 5-fluoro-2,4-dimethoxypyridine

158 g (1,00 M) 5-fluoro-2,4-dimethoxypyridine,150 g (3.00 M) of hydrazine hydrate, and 237 g of methanol were placed in a liter flask and heated to boiling (about 70oC) for 3.5 h, while stirring. The mixture became homogeneous, and then again heterogeneous, cooled to 0 to 5oC, and present the solids were isolated by vacuum filtration, washed with 150 ml of cold methanol and dried to obtain the assigned weight. Thus received 151,5 g (96% of theory.) target compound in the form of colorless needle-like crystals, so pl. 188 - 189oC.

NMR-data (DMSO-d6): :1H: of 3.77 (s, 3H), 4,28 (2H), 7,83 (d, J=3.6 Hz, 1H), 8,87 (1H),13C: 54,2 137,9, (d, J=CF=19.6 Hz), 141,5 (l (JCF=244,8 Hz), 154,3 (l, (JCFoC. To this mixture was added 68 g (067 M) of triethylamine, and then 34 g (0.68 M) of hydrazine hydrate, slowly while stirring and cooling at a temperature of 5 to 10oC. After all of hydrazine was added, and the mixture was stirred while cooling for a further 15 min and then left to warm it up. After one hour the resulting solids were isolated by vacuum filtration, and then washed with 100-ml portions of water and 50 ml ethanol. Thus was obtained 79,7 g (80% of theory. ) of target compound in the form of a white solid substance, so pl. 141 - 143oC.

Elemental analysis for C6H9FNO4O

Calculated,%: C 41,9; H 5,27; N 32,5

Found,%: C to 42.2; H 5,12; N 32,6

3. Getting 5-chloro-4-hydrazino-2-methoxypyridine

A solution containing 0.35 g (2.0 M) 5-chloro-2,4-dimethoxypyrimidine and 0.35 g (0.7 mm) of hydrazine hydrate in 2.9 g of methanol was heated under reflux for 8 h, while stirring. After cooling the mixture to precipitate formed. Then add water until until you have stopped the release of sludge, then this precipitate was isolated by vacuum filtration and was left overnight for drying air, resulting in the floor of the crystals in the cubic, that, obviously, is connected with the phenomenon of sublimation, melting point of the product was 172 - 173oC.

NMR-data (DMSO-d6) :1H: 3,85 (s, 3H), 4,50 (2H), of 7.97 (s, 1H), 8,7 (1H), 13C: 54,17; 105,40; 152,77, 159,39 and 163,39.

4. Getting 8-fluoro-5-methoxy-1,2,4-triazolo[4,3-C] -pyrimidine-3(2H)-thione

5-fluoro-4-hydrazino-2-methoxypyridine (15,81 g, 0,100 M), 47 g of methanol, 10.2 g (0,100 M) of triethylamine and 11.4 g (0.15 M) of carbon disulfide were combined and placed in a 250-ml flask in nitrogen atmosphere and at room temperature, and then stirred and got yellow heterogeneous mixture. After that, the mixture was cooled to 15oC in an ice bath. Then added hydrogen peroxide (12.5 g of a 30% aqueous solution of 0.11 M) using a syringe pump, syringe which was introduced into the flask through the gasket. The addition was continued for one hour under stirring and cooled to maintain the temperature equal to about 15oC. then the mixture was left to continue the reaction was heated for one hour, resulting in a received orange heterogeneous mixture, which was filtered under vacuum to remove solid sulfur. The filtrate was cooled in an ice bath and acidified by adding to 17.6 ml of 0.11 M) of 6.25 G. hydrochloric acid, diluted with 125 ml of water. The sweat which received 18,81 g (94% of theory.) target compound in the form of a whitish solid with so pl. 166oC (when Razlog.).

NMR-data (DMCO-d6) :1H: 4,01 (s, 3H), of 7.64 (d, J = 2,8 Hz, 1H), 14,5 (Shir. S., 1H);13C: 56,00, 125,6 (l( JCF= 22,0 Hz), 141,6, 141,7 (l( JCF= 41.7 Hz), 146,0 (l (JCF= 191,0 Hz)), and 161,2.

5. Getting 5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-c] -pyrimidine - 3(2H)-thione

Received a mixture containing approximately 5.2 g (30 mm) 2-ethoxy-4-fluoro-6-hydrazinopyridazine in a solvent consisting of 50 ml of acetonitrile and 15 ml of water, and to this mixture under stirring was added 6.4 ml (107 mm) of carbon disulfide at room temperature. After about 10 min the white heterogeneous mixture turned pale yellow solution, after which it for 30 min under stirring was added 3.8 ml (37 mm) 30% aqueous hydrogen peroxide solution and 3.2 ml of water, cooling to maintain the temperature of ~ 25oC. the resulting mixture was left to react for a further 10 min, then was added 3,22 g (32 mm) of triethylamine, and filtered to remove sulfur. The obtained filtrate was acidified by adding 10 ml (38 mm) 3,75 N. hydrochloric acid. After that, the mixture was filtered to highlight the formed precipitate. This precipitate was washed with water and dried, resulting in a received 4.4 g (66% of theory.) the target compounds, with 97% purity, in the ü in the filtrate.

Elemental analysis for C7H7FN4OS

Calculated,%: C 39,2; H 3,29; N 24,2,

Found,%: C 39,3; H of 3.07; N 25,9

6. Obtain 7-chloro-5-ethoxy-1,2,4-triazolo[4,3-c] -pyrimidine - 3(2H)-thione

A mixture containing 20 g (99 mm) at 93% pure 4-chloro-2-ethoxy-6 - hydrazinopyridazine in a solvent consisting of 90 ml of acetonitrile and 26 ml of water, was obtained in nitrogen atmosphere in a 500-ml flask, equipped with a refrigerator and a hole, covered by the gasket, through which he inserted the syringe specified pump. To the mixture was added 11.3 g (148 mm) of carbon disulfide and after 15 minutes of reaction to the reaction mixture via syringe while stirring for 15 min was added 16.7 g (147 mm) 30% aqueous hydrogen peroxide, cooling to maintain the temperature approximately 25oC. the resulting mixture was left to react for 4 h, and then cooled to approximately 0oC. the Precipitated product and the sulfur by-product was isolated using vacuum filtration, and then washed with water, mixture of water and acetonitrile (1:1) and finally with acetonitrile. The crude residue on the filter is suspended in 1 l of water at a temperature of 70oC, after which was added approximately 600 ml of acetonitrile to dissolve the solids. After filethe crystals were isolated by vacuum filtration, washed with acetonitrile, and then dried to constant mass and received 14.1 g (62% of theory.) target compound in the form of a solid amber color, which is decomposed at a temperature above 187oC.

Elemental analysis for C7H7ClN4OS

Calculated,%: C 36,4; H a 3.06; N 24,3

Found,%: C 36,4; H 2,79; N 24,1

7. Obtain 8-chloro-5-methoxy-1,2,4-triazolo[4,3-c]-pyrimidine - 3(2H)-thione

5-Chloro-4-hydrazino-2-methoxypyridine (17,45 g, 0.10 M) and 25 g (0,033 M) of carbon disulfide under stirring was combined with 120 ml of acetonitrile and 30 ml of water at room temperature, and then to the resulting mixture for 2 h under stirring was added 11.4 g (0.10 M) of 30% hydrogen peroxide. The temperature was increased from 20oC to 48oC. thereafter, the mixture was analyzed using liquid chromatography high pressure (ghvd), which indicated completion of the reaction. Part of the reaction mixture (79,8 g, 47.2 percent of the entire mixture) was diluted with 50 ml water and the mixture was acidified with hydrochloric acid. The resulting solids were isolated by vacuum filtration and dried, resulting in a received 10,15 g of a mixture of the target compounds and sulfur. Sulfur was removed by extraction solids using 45 g of carbon disulfide and (ghvd analysis) and decomposed when heated.

NMR (DMCO-d6) :1H: Android 4.04 (c, 3H), to 7.67 (c, 3H), 14,25 (Shir. S., 1H);13C: 56,18, 110,08, 140,46, 145,76, 150,11 and 161,32.

8. Getting 8-fluoro-5-methoxy[1,2,4-triazolo[1,5-c] pyrimidine - 2(3H)-thione

Received a mixture containing of 10.01 g (0,050 M) 8-fluoro-5-methoxy- [1,2,4] -triazolo[4,3-c] pyrimidine-3(2H)-thione and 8.6 g of methanol. After cooling in a bath of ice/water to the resulting mixture in a nitrogen atmosphere, with stirring and cooling was added sodium methoxide in methanol (32,4 g of 25% aqueous solution of 0.15 M). To the resulting thick suspension after 2.5 h under stirring was added 25,6 ml ice 6,26 n aqueous solution of hydrochloric acid. The mixture is then diluted with a small amount of water, and the solids were isolated by vacuum filtration and was dried under reduced pressure, resulting in a received compared to 8.26 g (83% of theory.) target compound as a colorless powder. The compound obtained melts at 155-160oC, and then is cured and does not melt already up to temperature 230oC.

NMR (CD3CN) :1H: 2,5 - 3,5 (Shir. S., 1H), 4,21 (s, 3H), 7,92 (d, J = 2.1 Hz)1H);13C: 57,4, 118,2, 129,2, 129,5, 143,0, 146,4, 146,7, 148,7, 149,1 and 163,8.

9. Getting 5-ethoxy-7-fluoro[1,2,4] triazolo[1,5-c] pyrimidine - 2(3H)-thione

Received a mixture of 5.8 g (26 mm) 5-ethoxy-7-ft and a temperature of 0oC was added to 12.2 ml (33 mm) 21 wt. % ethoxide sodium in ethanol, cooling at the same time. After this happened a mild exothermic reaction, which resulted in the mixture in suspension turned into a solution of a lead color. Then the mixture was stirred for 2.25 hours at a temperature below 10oC to complete the reaction. After acidification 25 ml of 1.25 N. hydrochloric acid and the mixture was stirred for 30 min at -10oC, and then filtered to highlight the formed precipitate. The precipitate was washed with 10 ml of cold water and drained, resulting in received 3.3 grams (60% of theory.) the target compound 98% purity. The second collection, the number of which amounted to 1.7 g (19% of theory.) material with a purity of 60%, was obtained from the filtrate. The target connection was so pl. 83,5oC - 86,5oC and consisted of a white solid.

NMR (CDCl3) :1H: was 1.58 (t, 3H), to 4.52 (s, 2H), 4.75 in (square, 2H), 7,28 (m, 3H), 7,45 (d, 2H).

In addition, the identity of the compounds was confirmed by processing it through benzylchloride, resulting in this connection turned into a 2-benzylthio-5-ethoxy-7-fluorescent[1,2,4] triazolo[1,5-c] - pyrimidine, T. pl. 78-82oC.

10. Obtain 8-chloro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimid the Ola and to this mixture, stirring at room temperature, was added in increasing amounts 0.26 g (1.2 mm) manufactured by industry 25% sodium methoxide in methanol. After 35 minutes the reaction mixture was acidified with an aqueous solution of hydrochloric acid, and then diluted with water. The precipitate was isolated by filtration and dried, resulting in received has 0.168 g of target compound with a purity of 97%, defined using ghvd, and represents a solid cream color. The compound obtained can be recrystallized from a mixture of methanol and water; it decomposes, but does not melt when up to temperature 250oC.

NMR-data (CDCl3)1H: 4,28 (s, 3H), of 7.93 (s, 1H), above 14 (not seen); 13C: 56,0, 112,0, 142,1, 148,0, 153,5 and 163,0.

In addition, the identity of the obtained product was confirmed by its transformation into a well-known compound (see U.S. patent No. 5 163 995), namely 2-benzylthio-8-chloro-5-methoxy[1,2,4] triazolo[1,5-c] pyrimidine, through the processing of this product benzylchloride.

11. Getting 2,2-dithiobis(8-fluoro-5-methoxy[1,2,4]-triazolo- [1,5-c]pyrimidine)

Received a heterogeneous mixture consisting of 76,0 g (0,380 M) 8-fluoro-5-methoxy[1,2,4]-triazolo[1,5-c]pyrimidine-2(3H)-thione and are hydrogen. As a result, proceeded exothermic reaction with increasing temperature up to 43oC. then the mixture was left to react for approximately 75 min, and then, stirring was added 13,0 g (0,115 M) ice 30 wt.% solution of hydrogen peroxide. The resulting mixture was left to react for another 30 min, and then the resulting solids were isolated by vacuum filtration. Thereafter, the solids were dried and suspended in methanol. The suspension was heated to boiling, cooled to 35-45oC and filtered to highlight nerastvorim solids. These solids were dried under reduced pressure at 40oC and received 61,9 g (80% of theory.) target compound in the form of a whitish solid. This compound was a white powder at a temperature of 201 - 208oC (decomposition).

NMR-data (DMSO-d6) :1H: 4,16 (s, 3H), 8,21 (d, J = 2.1 Hz, 1H).

12. Getting 2,2'-dithiobis(5-ethoxy-7-fluorescent[1,2,4]triazolo [1,5-c]pyrimidine

Received a solution of 2.9 g (13.5 mm) 5-ethoxy-7-fluoro-[1,2,4] - triazolo[1,5-C] pyrimidine-2(3H)-thione in 30 ml of acetonitrile, and to this solution, with stirring, in a nitrogen atmosphere at room temperature was added to 0.80 ml (7.8 mm) 30% peroxide water is and hour, and then added 15 ml of water, and the mixture was cooled to a temperature of -5oC. the Resulting precipitate was isolated by vacuum filtration, washed with two 10-ml portions of a mixture (1: 1) of water and acetonitrile in 5oC, and drained, resulting in the obtained 2.7 g (93% of theory.) target compound in the form of a light beige powder, so pl. 215 - 216oC.

Elemental analysis for C14H12F2N8O2S2< / BR>
Calculated,%: C to 39.4; H 2,83; N 26,3

Found,%: C to 39.6; H, 2.75; N 25,9

13. Getting 2,2'-dithiobis(5-ethoxy-7-fluoro[1,2,4] triazolo [1,5-c]pyrimidine) of 5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-C] pyrimidine-3(2H)-thione

Procedure A

Received a mixture of 167 g (0.67 M) 5-ethoxy-7-fluoro[1,2,4]-triazolo[4,3-C] pyrimidine-3(2H)-thione 1.67 liters of absolute ethanol denatured with toluene, and to this mixture under cooling and vigorous stirring was added 331 ml (0,887 M) 30% ethoxide sodium in ethanol at a temperature of 0oC. the Reaction proceeded with a small ekzotermicheskie, and the heterogeneous mixture is a light beige color developed in the solution is leaden. This solution was maintained at a temperature of from 5oC to 10oC for 2.25 hours, and then acidified with 150 ml of 6.25 G. hydrochloric acid, diluted 685 ml of water. Yali 43,4 ml (0,43 M) aqueous solution of 30% hydrogen peroxide. The temperature was increased to 33oC, and after 30 min, the whole tihonovy starting material was consumed, as evidenced ghvd. After that, the mixture was cooled to 20oC, and besieged the target compound was isolated by filtration, and then washed with 5oWith two 600-ml portions of water and 350 ml of an aqueous solution of 50% ethanol. The obtained white solid was dried under reduced pressure at 35oC, and received 154 g (86% of theory.) the target compounds, having a purity of about 90% (ghvd analysis).

Procedure B

A solid mixture having a purity of 68%, which was confirmed by the analysis, and containing 1,89 including 5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-C]pyrimidine-3(2H)-thione, together with sulfur, less than 2% water, and a certain amount of acetonitrile was dissolved 8,61 hours of absolute ethanol, and the resulting mixture was cooled to 10oC. To this mixture, stirring, was added a 21 wt.% ethoxide sodium in ethanol (3,21 hours ), and after a few minutes, the mixture was filtered to remove sulfur, and the filtrate was left. Then sulfur washed 0,484 hours of absolute ethanol, and filtered wash ethanol was added to the filtrate. Filtrate the mixture was left for reaction at 10oC as long as the isomerization was not fully saviodsilva solution of 37% hydrochloric acid. Then to this mixture, stirring and cooling to maintain the temperature below 30oC, was slowly added 30 wt.% the hydrogen peroxide solution in water (0,602 hours ), and after complete addition the mixture was stirred for another 30 minutes the precipitate was isolated by filtering in the device operating at reduced pressure, and washed 3,40 including ethanol and 8,70 including water, resulting in the obtained target compound in the form of hydrated solids.

14. Getting 2,2'-dithiobis (5-ethoxy-7-fluoro[1,2,4]-triazolo [1,5-C]pyrimidine) of 4,6-debtor-2-ethoxypyridine

Mixture of 32.7 g (0,202 M) 2-ethoxy-4,6-deflorationvirgin, 59 g of acetonitrile and 36 g of water received in the reaction vessel, and then the resulting mixture was stirred in nitrogen atmosphere and cooled to approximately 5oC. To this mixture was added to 21.3 g (0,208 M) of triethylamine, and then stirring and cooling at such a speed, at which is provided by maintaining the reaction temperature below 15oC, was added 10.6 g (0,208 M) monohydrate of hydrazine. After all of hydrazine monohydrate was added, and the heat began to subside, the mixture was left to warm to room temperature to complete the reaction. Thus, the Colo 95 g).

The resulting solution of 2-ethoxy-4-fluoro-6-hydrazinopyridazine in aqueous acetonitrile were placed in a reaction vessel, and while stirring, in a nitrogen atmosphere, was added 23.1 g (0,303 M) of carbon disulfide. After about 15 min to the solution, stirring and cooling to maintain the temperature at approximately 25 - 30oC, was added to 23.8 g (0,210 M) aqueous solution of 30 wt.% of hydrogen peroxide. The result of this procedure were formed precipitate. Then the mixture was left to react for approximately 1 h, then was cooled to 0oC. This mixture was filtered to precipitation. Then the precipitate was washed with two 75-ml portions of cold water to remove impurities, and then washed with two 50-ml portions of cold acetonitrile to remove the water. It was found that 48.7 per g of the obtained solid material contains 71% 5-ethoxy-7-fluoro-1,2,4-triazolo-[4,3-C] pyrimidine-3(2H)-thione (ghvd analysis) (35 g, 80% from Teoret.) and less than 2% water (titration Karl Fischer). The main impurity was elemental sulfur as a byproduct.

of 48.7 g (0.16 M) 5-ethoxy-7-fluoro-1,2,4-triazolo[4,3-C] - pyrimidine-3(2H)-thione, representing 71% mixture of sulfur and acetonitrile, as described above, was combined with 150 g of dry way the temperature ranged from 5 to 15oC, was added 67,7 g (0.21 M) 21% ethoxide sodium in ethanol. the pH of the resulting mixture was approximately 12. After that, the mixture was filtered to remove nerastvorimaya solid sulfur, and sulfur was then washed with 20 g of dry ethanol. The filtrate (including wash ethanol) was left for reaction at a temperature of approximately $ 7oC approximately 2 h, after which was added to 21.7 g (0.22 M) of concentrated hydrochloric acid and was obtained 5-ethoxy-7-fluoro-[1,2,4]triazolo-[1,5-C] pyrimidine-2(3H)-tion in the form of a light beige solid in ethanol.

The above mixture of 5-ethoxy-7-fluoro-[1,2,4]triazolo-[1,5-C]pyrimidine-2(3H)-thione in ethanol, stirring, was treated and 22.6 g (0,199 M) 30% hydrogen peroxide at room temperature. These were followed by a weak exothermic reaction. After 40 minutes of reaction the mixture was filtered to precipitation. This precipitate was washed with two 100-ml portions of ethanol and two 100-ml portions of water, and then dried at a temperature of 37oC under reduced pressure and got 30,9 g (65% of theory. 2 ethoxy-4,6-liftability) of target compound (purity, 90%) as a pale brown solid substances is 7-fluoro-[1,2,4]triazolo [1,5-C]pyrimidine

Procedure A

Received a mixture containing 53,3 g (0,11 M) 88% pure 2,2'-dithiobis(5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-C]pyrimidine), 483 g of dichloromethane, and 12.0 g of water, and then the mixture was cooled to approximately 5oC. Chlorine (42.5 g, 0.60 M) was barbotirovany in the mixture, cooling and stirring for 2.5 h, so that the temperature did not rise higher than about 15oC. during the addition of chlorine was added to 37.1 g of water. Initially present solid at first, becoming more dense, and then basically they all turned in the solution. The resulting mixture was diluted with about 200 ml water and the phases were separated. The organic phase having Golden color, washed with three 400 ml portions of water, dried with magnesium sulfate, filtered and concentrated by evaporation under reduced pressure and at a bath temperature of up to 38oC. Target compound contained in the residue, the number of which amounted to a total of 59.5 g (96% of theory.) and that was a waxy Golden yellow solid. Part of this residue (12,66 g) was purified by dissolving in approximately 30 ml of dichloromethane, followed by adding about 30 ml of hexane and cooled. Formed Stacie was obtained, and 3.16 g of the second collection. This product is identified by spectroscopy, which indicated the similarity of this compound with the compound described in U.S. patent N 5163995.

Procedure B

A mixture containing 212,5 g (0,44 M) 88% pure 2,2'-dithiobis(5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-C]pyrimidine), 19,85 g of dichloromethane, and a 99.0 g of water was obtained in the reaction flask and the mixture was cooled to approximately 5oC in a bath of water/dry ice. 170 g (2.4 M) of chlorine was completely introduced into the flask above the liquid level, cooling and stirring so that the temperature did not rise above approximately 15oC. Initially present solid at first, becoming more dense, and then basically they all turned in the solution. The resulting mixture was diluted with approximately 300 g of cold water and 220 g of cold 6,25 N. hydrochloric acid, after which the phases were separated. The organic phase having Golden color, dried magnesium sulfate, filtered, concentrated by evaporation under reduced pressure, and then dried in an oven operating at reduced pressure, at room temperature. Thus was obtained 201,6 g (74,5% of theory.) target compound with a clean 91% (ghvd analysis) in the form of a Golden yellow solid.


A mixture containing 3.7 g (17.3 mm) 5-ethoxy-7-fluoro[1,2,4] triazolo[1,5-C] peridinin-2(3H)-thione, 45 ml of dichloromethane and 15 ml of water were placed in a three-neck flask equipped with a mechanical stirrer, an output tube connected to the alkaline scrubber inlet tube for chlorine inlet and a cooling bath. A complete solution was not obtained. Then to the solution at 0oC, stirring and cooling were introduced 7.0 g (99 mm) of chlorine. All solids were dissolved. Aqueous and organic layers were separated, then the organic layer was dried with magnesium sulfate, concentrated by evaporation under reduced pressure, and obtained target compound as a residue. The isolated product, the number of which amounted to 3.6 g (75% of theory.), was an orange solid with a purity of about 88%. The compound obtained was identified by spectroscopy in a manner analogous to the method described in U.S. patent N 5163995.

5-Alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2 (3H)-tinove connection formulas

< / BR>
where one of Y and Z represents F, Cl, Br, and the other represents H,

R represents a CH3or C2H5.

2. Connection on p. 1, where one of Y and Z represents Cl or F, and the other of preds-5-methoxy [1,2,4] -triazolo [1,5-c] pyrimidine-2(3H)-tion, 5-ethoxy-7-fluoro- [1,2,4] triazolo [1,5-c] pyrimidine-2(3H)-tion and 8-chloro-5-methoxy-[1,2,4]-triazolo [1,5-c] pyrimidine-2(3H)-tion.

4. The method of obtaining 2-chlorosulfonyl-5-alkoxy[1,2,4]-triazolo[1,5-c]pyrimidine of the General formula

< / BR>
where one of Y and Z represents F, Cl, Br, and the other represents H;

R represents a CH3or C2H5,

characterized in that 5-alkoxy [1,2,4] triazolo [1,5-c]pyrimidine-2(3H)-tion formula

< / BR>
where R, Y, and Z are defined above,

process at least one equivalent of the appropriate oxidizing agent in an inert reaction medium, resulting in a gain of the intermediate compound, namely 2,2'-dithiobis(5-alkoxy [1,2,4]triazolo [1,5-c] pyrimidine) formula

< / BR>
where R, Y, and Z are defined above,

and then, the resulting intermediate compound is treated with at least 5 moles of chlorine in an appropriate reaction medium, in terms of going for conducting oxychlorination process, obtaining 2-chlorosulfonyl-5-alkoxy [1,2,4] triazolo [1,5-c] pyrimidine.

5. The method according to p. 4, characterized in that the oxidizing agent chosen from hydrogen peroxide, halogen.

6. The method according to p. 5, characterized in that, as specified okislyayutsya at a temperature of from -10 to 30oC and/or oxidation is carried out at a temperature from 0 to 40oC.

8. The method according to p. 4, characterized in that the processed 5-alkoxy [1,2,4] triazolo[1,5-c] pyrimidine-2-(3H)-tinove connection, in which one of Y and Z represents F or Cl, and the other represents H.

9. The method according to p. 8, characterized in that the processed one of the following compounds: 5-ethoxy-7-fluoro[1,2,4] triazolo [1,5-c]pyrimidine-2-(3H)-tion, 8-fluoro-5-methoxy[1,2,4] triazolo[1,5-c] pyrimidine-2-(3H)-tion and 8-chloro-5-methoxy[1,2,4]triazolo [1,5-c]pyrimidine-2(3H)-tion.

10. The way to obtain 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo [1,5-c]pyrimidine of the General formula

< / BR>
where one of Y and Z represents F, Cl, Br, and the other represents H;

R represents a CH3or C2H5,

characterized in that 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-tion formula

< / BR>
process at least one equivalent of the appropriate oxidizing agent in an inert reaction medium.

11. The method according to p. 10, characterized in that the oxidizing agent chosen from hydrogen peroxide, halogen.

12. The method according to p. 11, characterized in that the oxidizing agent is hydrogen peroxide.

13. is audica fact, what in the received connection one of Y and Z represents F or Cl, and the other represents H.

15. The method according to p. 14, wherein one of the compounds obtained is 2,2'-dithiobis(5-ethoxy-7-fluorescent[1,2,4] triazolo [1,5-c]pyrimidine), 2,2'-dithiobis(8-fluorescent-5-methoxy [1,2,4] triazolo[1,5-c]pyrimidine and 2,2'-dithiobis(8-chloro-5-methoxy [1,2,4]triazolo[1,5-c]pyrimidine).

16. 2,2'-Dithiobis(5-alkoxy [1,2,4] triazolo[1,5-c]pyrimidine) formula

< / BR>
where one of Y and Z represents F or Cl, Br, and the other represents H;

R represents a CH3or C2H5.

17. Connection on p. 16, in which one of Y and Z represents F or Cl, and the other represents H.

18. Connection on p. 17, which represents one of the following compounds: 2,2'-dithiobis(5-alkoxy-7-fluorescent[1,2,4]triazolo[1,5-c]pyrimidine), 2,2'-dithiobis(8-fluorescent-5-methoxy[1,2,4] triazolo[1,5-c] pyrimidine and 2,2'-dithiobis(8-chloro-5-methoxy [1,2,4]triazolo[1,5-c]pyrimidine).

19. The method of obtaining 2-chlorosulfonyl-5-alkoxy[1,2,4] triazolo[1,5-c] pyrimidine of the General formula

< / BR>
where one of Y and Z represents F, Cl, Br, and the other represents H;

R represents a CH3or C2H5,

different is shown above,

process at least 5 moles of chlorine in an appropriate reaction medium under conditions suitable for conducting oxychlorination process.

20. The method according to p. 19, characterized in that the reaction is carried out at a temperature of -10 to 30oC.

21. The method according to p. 19, wherein the processed connection, namely 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine), where one of Y and Z represents F or Cl, and the other represents H.

22. The method according to p. 21, wherein the processed connection, namely 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine), where R represents ethyl.

23. The method according to p. 21, characterized in that one of the processed compounds: 2,2'-dithiobis(5-alkoxy-7-fluorescent[1,2,4]triazolo[1,5-c]pyrimidine), 2,2'-dithiobis(8-fluorescent-5-methoxy[1,2,4] triazolo[1,5-c] pyrimidine) and 2,2'-dithiobis(8-chloro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine.

 

Same patents:

The invention relates to new chemical compounds with valuable properties, in particular to derive hinolan and naphthyridinone acid of General formula

< / BR>
in which

A is CH, CF, CCl, C-OCH3C-CH3N;

X1hydrogen, halogen, NH2CH3;

R1alkyl containing 1 to 3 carbon atoms, FCH2CH2- cyclopropyl, phenyl, which can be from one to three times substituted by halogen, or

A and R1together can mean the bridge structure C-O-CH2-CH(CH)3,

R2hydrogen, not substituted or substituted by a hydroxy-group, halogen or amino alkyl containing 1 to 3 carbon atoms, or 5-methyl-2-oxo-1,3-dioxol-4-yl-methyl;

B balance formulas

< / BR>
where

Y is O or CH2;

R3oxaalkyl containing 2 to 5 carbon atoms, CH2-CO-C6H5CH2CH2CO2R', R O2C-CH=-CO2R', -CH=CH-CO2R' or CH2CH2-CN, where R' denotes hydrogen or alkyl containing 1 to 3 carbon atoms;

R4hydrogen, alkyl containing 1 to 3 carbon atoms, окMG SRC="http://www.fips.ru/fullimg2/rupat3/19981/010.dwl/2105770-6t.gif" ALIGN="ABSMIDDLE">CH=CH-CO2-R' or CH2CH2-CN or 5-methyl-2-oxo-1,3-dioxol-4-yl-methyl, where R' denotes hydrogen or alkyl containing 1 to 3 carbon atom,

in the form of mixtures of isomers or individual isomers, pharmaceutically applicable hydrates and salts, for example acid additive salts and alkaline, alkaline earth, silver and guanidinium salts of the corresponding carboxylic acids

The invention relates to pharmaceutically active bicyclic heterocyclic amines (XXX) and can be used as pharmaceuticals for the treatment of diseases and injuries

The invention relates to fungicidal compositions, a new derivative of triazolopyrimidine, method of production thereof and method of combating fungi

The invention relates to a derivative triazolopyridine and their salts, method of production thereof, intermediates and pharmaceuticals

The invention relates to a derived benzazepine with condensed nitrogen-containing aromatic 5-membered cycle, represented by formula I

,5,6]-6-amino-3-azabicyclo [3.1.0] gex-3-yl)- 6-fluoro-1-(2,4-differenl)-1,4 - dihydro-4-oxo-1,8 - naphthiridine-3-carboxylic and methanesulfonic acid and its preparation" target="_blank">

The invention relates to a new form of the anhydrous salt methanesulfonic acid and 7-([1,5,6]-6-amino-3-azabicyclo[3.1.0] Gex-3-yl)-6-fluoro-1-(2,4-differenl)- 1,4-dihydro - 4-oxo-1,8-naphthiridine-3-carboxylic acid, to a method of use of the compounds in the treatment of bacterial infections in mammals, especially humans, and to pharmaceutical compositions useful for him

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

20 cl, 6 tbl, 192 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to improved synthesis method of pyrlindone hydrochloride having formula (I) 1. Method features intramolecular cyclization of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole hydrochloride of formula IV 2 at 80°-140°C with alkali agent in presence of phase transfer catalyst to provide 1,2,5,6-tetrahydro-8-methyl-pyrazine[3,2,1-j,k]-4H-carbazole of formula VI 3 followed by reduction at 80°-120°C. Method of present invention makes in possible to produce compound of formula I with yield nearly 70 % and purity more than 99 %.

EFFECT: method of high yield with reduced amount of alkali agent and phase transfer catalyst.

7 cl, 2 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to novel pyrasolbenzodiazepines of formula I 1 (in formula R1 is hydrogen, -NO2, -CN, halogen, -OR5, -COOR7, -CONR8R9, -NR10R11, NHCOR12, NHSO2R13; each R2 and R4 independently of one another are hydrogen, halogen, -NO2, -CF3; R3 is hydpegen, C3-C8-cycloalkyl, aryl, in particular C6-C10-aromatic group having 1 or 2 rings, 5-10-membered heteroaryl, having 1 or 2 rings and1-3 heteroatoms, selected from N, O, and S, -COOR7, CN, C2-C6-alkenyl, -CONR8R9 or C1-C6-alkyl optionally substituted with OR9-group, F or aryl as mentioned above; R5 is C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; each independently of one another are hydrogen or C1-C6-alkyl optionally substituted with hydroxyl or NH2, or alternatively R8 and R9 together form morpholino group; each R10,R11 and R12 independently of one another are hydrogen or C1-C6-alkyl; R13 is C1-C6-alkyl optionally substituted with halogen or -NR14R15; each R14 and R15 independently of one another are hydrogen or C1-C6-alkyl optionally substituted with halogen; or alternatively -NR14R15 is morpholino group) or pharmaceutically acceptable salts thereof, as well as to certain pyrasolbenzodiazepine derivatives, thiolactam intermediates for production of compound (I) and pharmaceutical compositions containing the same. Compound and pharmaceutical composition of present invention are cycline-dependent kinase (CDK2) inhibitors and antiproliferation agents used in treatment or controlling disorders associated with cell proliferation, in particular breast, colon, lung and/or prostate tumors.

EFFECT: new antiproliferation agents.

20 cl, 12 tbl, 8 ex

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