PL141382B1 - Method of obtaining novel derivatives of 4-amino/1,2,4/thiazolo/4,3-a/quinoxaline - Google Patents

Description

The present invention relates to a process for the preparation of novel 4-amino- [1,2,4] triazolo [4,3-a] quinoxaline derivatives and their pharmaceutically acceptable acid addition salts which are useful as antidepressants and anti-fatigue agents. There has long been a need and there has been a long history of intensive research into finding agents that effectively combat signs of depression and fatigue in mammals. US Patent No. 3,839,569 discloses the use of [4,3-a] quinolines, and German Patent No. 2 249 350 application of lH-imidazo [4,5-b] quinoxaline derivatives as fungicides in agriculture. US Patent No. 4,008,322 describes the use of triazolo [4,3-a] quinoxaline derivatives for the control of rice blight caused by the phylopathogen Piricularia oryzae. The invention relates to the preparation of new 4-amino- [1] derivatives. , 2,4] triazolo [4,3-a] quinoxalms, useful as antidepressants and anti-fatigue agents represented by the general formula 1, optionally in the form of pharmaceutically acceptable acid addition salts, wherein X and Xi independently of each other are hydrogen, fluorine, chlorine, bromine or methoxy; Ri represents a hydrogen atom, a lower alkyl group, a lower perfluoroalkyl group or a phenyl group; and R2 and Rj independently from each other represent a hydrogen atom, a lower alkyl group, a phenylalkyl group containing 1-3 carbon atoms in the alkyl part or an acyl group with 2 to 5 carbon atoms, provided that at least one of R2 and Rs represent a group different from hydrogen when X and Xi are simultaneously hydrogen atoms, and Ri is hydrogen or a methyl group, or R2 and R 'together form a piperazine ring. The lower alkyl group denotes an alkyl group containing 1-4 carbon atoms, and the lower perfluoroalkyl group means a perfluoroalkyl group having 1-4 carbon atoms, such as trifluoromethyl or pentafluoroethyl etc. There is an interesting group of compounds falling within the scope of the invention which includes compounds of formula I wherein X and Xi are each a hydrogen atom, Ri is a hydrogen atom, and R2 and Rs are each lower alkyl, preferably R2 and R8 each represent an ethyl group. Another group of compounds of the present invention is includes compounds of formula I wherein X and Xi are each hydrogen, Ri is ethyl and Rs is lower alkyl. Compounds in which R2 is hydrogen and Rs is ethyl are preferred. Another group of compounds according to the invention comprises those compounds of formula I wherein X and X1 each represent a hydrogen atom, R1 is a lower alkyl group and Rs is an acetyl group. Compounds in which Ri is an ethyl group and R2 is hydrogen, ethyl or acetyl are preferred. The invention includes those compounds of the formula S, in which at least one '% sWf} $} jftNriif) y / i J $ i xi is a fluorine atom, Ri k ^ "nT ^ ijatopj ^" - or a trifluoromethyl group , Rt is 'hydrogen' and R1 is hydrogen, lower alkyl or acyl group of 2-5 carbon volumes; or compounds in which at least one of X and Xi is chlorine, Ri is a lower alkyl group, summer, a trifluoromethyl group, R * is a hydrogen atom and R * is a hydrogen atom, a lower alkyl or acyl group of 2 to 5 carbon atoms. The method according to the invention is that the corresponding 4-chloro derivative is of formula 2a or 2b, in which X, XA and R 1 are as defined above, are reacted with an amine of formula HNRtRj, in which Rt and R 1 are as defined above, except for the acyl group, to give the corresponding derivative 4 - amino, which optionally, if cq at least one of R2 and Rs is hydrogen, is reacted with anhydrous with the corresponding alkanecarboxylic acid to give the 4-amino derivative with the acyl moiety, and optionally convert the compound obtained from general formula I to its pharmaceutically acceptable acid addition salt. Most of the new compounds of formula I are obtained with The compounds of formula IIa obtained in turn by the series of reactions shown in Scheme 1. The method for the numbering of the phenyl ring and the three heterocyclic rings shown therein is provided throughout the description. According to Scheme 1, the compound of formula IV is is a derivative of quinoxaline in which XiXj independently of each other represent a hydrogen atom, a fluorine atom, a chtom, a thorium atom or a reethoxy group, with the proviso that when the latter has one substituent on the beraean piersefeRl, X represents a hydrogen atom, it produces an hydrous hydrate of hydrazine in a neutral organic body which is neutral to the reaction, such as an alkanol containing 1 to 3 carbon atoms, preferably in ethanol , at room temperature, for about 18-24 hours, to form an intermediate compound of formula 3, the intermediate compound of formula 3 can then be converted into the corresponding intermediate of formula 2a, in which Ri has a different meaning the lower perfluoroalkyl group by reacting it with the appropriate alkyl ester of an orthobenzoic acid or an alkyl ester of orthobenzoic acid as needed at a temperature of about 80-120 ° C for about 1-24 hours. In the compound of formula IIa obtained as a result of this reaction, the type of the R 1 substituent (hydrogen atom or alkyl group) depends on the type of the ortho-alkylcarboxylic ester of which the synthesis was used. For example, a compound of formula IIa is obtained with triethyl orthoformate, where Ri is hydrogen, a compound with triethyl orthopropionate is obtained in which Ri is ethyl, and with orthoisobutyrate a compound in which R 1 is isopropyl is obtained. An intermediate of formula III can be converted into the corresponding intermediate of formula IIa, in which R 1 is a lower perfluoroalkyl group by treatment with an excess of the appropriate acid perfluoroalkanecarboxylic acid such as trifluoroacetic acid or pentafluoropropionic acid etc. by known method to obtain the corresponding 4-hydroxy-1-perfluoroalkyl [1,2,4] triazol [4,3-a] quinoxaline, which in turn treated with phosphorus oxychloride in the presence of a tertiary amine, for example triethylamine, at elevated temperatures gives the corresponding 4-chloro derivative. Formula IIa intermediate, where Ri is hydrogen, the lower alkyl group, the perfluoroalkyl lower group or the phenyl group are then converted to the 4-amino [1,2f4] triazolo {4,3-a] quinoxaline derivative of formula Ia, in which "Rf and RfSnaja are given above meaning that Re and Ba are substituents other than the acyl group, by treatment of an excess of the amine of formula HNRjRf in a reaction-neutral organic solvent, preferably in N, N-dimethylformamide, at a temperature of about 0-60 ° C, within 2-4 hours. Thus, for example, the preferred compounds of Formula Ia in which R2 and R8 are both ethyl groups are obtained by reactions; the corresponding compound of formula IIa with diethylamine in N, N-dimethylformamide at room temperature for 2-3 hours. Likewise, the preferred compounds of formula Ia in which R2 is hydrogen and R1 is ethyl are obtained by reacting a compound of formula Z with monoethylamine in N, N-dmththiophymamide at room temperature at room temperature. for 4-5 hours. 4-amino- [1,2,4] triazolo [4,3-a] quinoxaline derivatives of formula Ia, in which at least one of R2 or Rt is an acyl group of 2-5 carbon atoms are obtained from the corresponding compounds of formula Ia in which at least one of R2 or Ri is hydrogen by reacting them with the anhydride of the appropriate alkanoic acid under anhydrous conditions. The reactions can be carried out in the presence of an organic base, such as a tertiary amine, acting as a Tole catalyst (although not absolutely necessary), over a temperature range of about 20 ° to 140 ° C for a period of half to 24 hours. The molar ratio of the acid anhydride to the starting 4-amine derivative should be at least 1: 1, preferably 4: 1 to 25: 1, while the amount of tertiary amine used is usually 25 to 150% by weight. an acylating agent (a tertiary amine can also be used as the reaction solvent by using it in excess). Although it is possible to carry out the reaction without a solvent, and in some cases even highly advantageous, the use of an appropriate organic solvent which is neutral under the reaction conditions may sometimes be necessary. Suitable organic solvents. which can be used in the above reaction are reaction-neutral, anhydrous organic solvents such as acetone, methyl ethyl ketone, benzene, toluene, xylene, dioxane, tetrahydrofuran, methylene chloride, chloroform, dichloroethylene, tetrachloroethane , methyl acetate, ethyl acetate, isopropyl acetate, methyl propionate, ethyl propionate, diethyl ether, isopropyl ether, n-propyl ether and the like. As stated above, the reactions can usually be carried out without a solvent using Just an excess of acid anhydride. Also, an excess of the tertiary amine used can serve as a solvent. Preferably as tertiary amines that can act as dissolution As a solvent and / or catalyst in this reaction, use is made of triethylamine, dimethylaniline, pyridine, picoline, lutidine, collidine and quinoline. The starting materials of Formula IV, where X and Xi each are hydrogen, are well known. Compounds of formula 4 in which Xi is methoxy can be obtained by the method described by GWN Cheeseman (J. Chem. Soc. P. 1170 (1962)) by reacting 4-methoxy-O-phenylenediamine hydrochloride with at least an equimolar amount of diethyl oxalate and diethylamine in an inert gas atmosphere, preferably nitrogen, at reflux temperature under reflux for 2-3 hours, followed by treatment with phosphorus oxychloride in the environment of a tertiary amine, preferably dimethylaniline, at the reflux temperature for 1-2 hours. According to scheme 2, the quinoxaline derivative of formula 4, where X is fluorine, chlorine, bromine or methoxy, and Xi is hydrogen, the mixture is treated with sodium methoxide in an alcoholic solvent and at a slightly elevated temperature (e.g., 40-60 ° C.) for about 6-60 ° C. 18 hours, to form the corresponding 2-chloro-3-methoxyquinoxaline derivative of formula V, which is then treated with hydrazine hydrate as described above to give the corresponding 2-hydrazine-3-methy derivative the oxyquinoxalines of formula 6. The intermediate of formula 6 is then converted to the 4-methoxy [1,2,4] triazolo [4,3-a] quinoxaline derivative of the 7-position of formula 7 using the appropriate orthoester or perfluoroalkanecarboxylic acid, as described above. The compound of formula 7 is then converted into the corresponding 4-hydroxy derivatives (see formula 8) - and 4-chlord derivatives by known methods to give the compound of structure 2b, which X has the meaning given above (i.e. other than hydrogen) and Xi is hydrogen. From such an intermediate of formula IIb then the corresponding new end compounds of formula Ib are obtained, where Ri, R2 and Rg have the same meaning as previously defined, and X and X2 are the meaning given above, following the reaction described in the last steps of general scheme 1. The invention also includes pharmaceutically acceptable acid addition salts of the novel compounds of formula 1. These salts are obtained by contacting the free base with a suitable mineral acid. or organic in an aqueous solution or in a suitable organic solvent. The salt can then be isolated in solid form by precipitation or distillation with a solvent. Pharmaceutically acceptable acid addition salts within the scope of the invention are, for example, hydrochlorides, sulfates, water. adult sulphates, mesylates, tosylates, nitrates, phosphates, acetates, lactates, maleates, fumaphanes, citrates, tartrates, succinates and gluconates any and the like, mesylates are preferred. If necessary, compounds of formula I can be obtained as the free base from their acid addition salts by treatment with a suitable base by subsequent extraction of the free base with a suitable organic solvent. Compounds of formula I and their pharmaceutically additive compounds Acid addition salts are active antidepressants and anti-fatigue agents and are therefore useful in the treatment of symptoms associated with depression and fatigue. These compounds may be administered by various conventional means, for example orally and parenterally. Preferably the compounds are administered orally. Typically, they are administered orally in one or more doses in an amount of from about 0.1 to 100 mg / kg of the patient's body weight per day, preferably from about 0.5 to 10 mg / kg per day. parenterally, these compounds are then administered in doses of from about 0.1 to 10 mg / kg of body weight per day, but some variation in doses may be necessary, depending on on the condition of the patient and on the relationship. These compounds. can be administered neat or in combination with pharmaceutically acceptable carriers or diluents as a single dose or over a series of doses. Suitable pharmaceutical carriers are neutral diluents or fillers, sterile aqueous solutions and various organic solvents. The pharmaceutical compositions prepared by combining the new compounds of general formula I or their salts with pharmaceutically acceptable carriers can be conveniently administered in the form of tablets, powders, capsules, lozenges, syrups and the like. Such pharmaceutical compositions may moreover contain additional ingredients such as flavorings, binders or excipients. Thus, tablets for oral administration may contain various excipients such as sodium citrate, various disintegrants such as starch, alginic acid and some complex silicates, and binders such as polyvinylpyrrolidone, sucrose, gelatin and gum. Arabic. The activity of the compounds according to the invention as anti-depressant and anti-fatigue agents was determined using various standard pharmacological tests, such as, for example, the so-called learned helplessness according to the Porsdlf model, that is, the motionlessness induced in rats during forced swimming (R.D. Porsolt et al., European J. Pharmacol., 47, 379 (1978)). It is known that pharmaceuticals of this type, effective in human treatment, reduce the degree of immobility induced by forced swimming according to the above model. The study of antidepressant activity against violent seizures in rats is a modification of the method described by R.D. Porsolf et al. in the European Journal of Pharmacology, Vol. 47, p. 379 (1978), which uses the individual observation, developed for mice by Wallach and Hedley [Comm. Psychopharm. Vol. 3, p. 35 (1979)]. According to the original Porsolf method, male Sprague-Dowley rats (Charles River) weighing 280-325 g are placed in individual plastic cylinders (45 cm high and 22 cm in diameter). cm) filled with water at 25 ° C. to a height of 25 cm. On the first day, the rats are placed in the cylinder for 15 minutes for training. During the first 10 minutes, the rats are observed to swim around in a typical manner, looking for an escape route. At the end of the fifteen-minute period, the rats, having experienced the hopelessness of their escape, assume a stationary stance and stay afloat until howl. 24 hours after the initial training, the animals are dosed orally with the vehicle or test compound, and about 1 hour later they are placed back in the water cylinder. A 90 vol.% Mixture is used as the carrier. saline (0.9% sodium chloride aqueous solution), 5 vol. ethanol and 5 vol. Emulphor. The preparation with the test compound is made by dissolving or suspending the test compound in ethanol and Emulphor followed by dilution with physiological saline. 8 Beginning the second minute after immersion, the rats are scored every 30 seconds for their desire to find an escape route over a total of ten observations. If the rat remains stationary and passively afloat, it receives a score of "1" as stationary. If, on the other hand, the rat behaves as if it is looking for an escape route from the tank (swimming vigorously or diving) it receives a score of "0". All rats are assessed within 30 seconds. Thus, based on a series of ten observations, a rat completely motionless for the duration of the trial is rated "10", while a rat showing an urge to escape is rated lower. Most rats that receive a vehicle receive a score of 8— 9, while the administration of an antidepressant reduces their immobility (antagonizes the state of resignation and "hopelessness") in a manner dependent on the dosage and duration of administration. In such conditions, the relationship is considered active if there is a difference between the behavior of the treated animals and control animals (ie, those that have received only the carrier alone) can be considered statistically significant compared to the results obtained by known standard measures such as REM sleep suppression and electroshock (ECS). In other words, the compound is considered to be active if there is a statistically significant decrease in immobility. Accordingly, the following [1,2,4] -triazolo [4,3-a ] -quinoxalin-4-amine of formula 1 in antidepressant activity against violent attacks in rats - using the modified swimming test described above by Porsolf et al., which were found to be active orally at the doses given below. The compound defined in the first line in which X, X1, Ri, R2 and Rs are each hydrogen is described in US Patent No. 4,008,322 as a blight control agent. 40 7-X 1 HH Cl HFH OCH3 HFH OCH3 HHFHF 8-Xx 2 HH Cl HFHHHFHHHHFF Ri 3 HHHHHHHHHHHHHHH R2 4 HHHHHHHHHHHHHHHH R3 5 HHHHHH COCH3 COCH Q3 5 HHHHHH COCH3 COCH Q3 5 HHHHHH COCH3 COCH Q3 5 HHHHHH COCH3 Q3, DCH3 32 mg COOH * 32 * 32 * 32 32 32 32 32 • 3,2 32 * 3,2 321 I 2 I 3 HH Cl HF OCH3 HHHH Cl H ~ FHHHH ¦ HHHH Cl H Cl FH Cl H Cl FHHHHHH Cl H 1 F 1 HHH Cl H F. "h HH Cl H" ci H ~ F ~ H Cl HHHHHHHH Cl Cl FFHH Cl HHHFF Cl Cl Cl H Cl H Cl HH Cl Cl HHH Cl Cl HF Cl Cl Cl HHH Cl HFH Cl Cl FFHHHH Cl Cl FF OCH3 Cl HH Cl Cl F 1 Cl FHHHHHHHHHHHHHHH CH3 CH3 'CH3 CH3 CH3 CH3 C2H5 C2H5 C2H5 C2HB C2H5 C2H6 C2H5 QH5 C2H5 C2H5 C2H6 QH5 C2H5 QH5 C2H5 C2H5 C2 QH5 C2H5 QH5 C2H5 C2 QH5 C2H5 QH5 C2H5 C2 QH5 C2H5 QH5 C2H5 QH5 -C3H7 iso-C3H7 C2H5 CF3, CF3 CF3 CF, HHHHHH COCH3 COCH3 CH3 C2H5 C2H5 QH5 QH5 iso-C8H7 | HHHH QH5 C2Ws HHHHHHHHHHHHHHHHHHHHH HHHH COCH3 C2H5 CH3 CH3 C2H5 C2H6 QH5 C2H5 C2H5 iso-C8H7 LZ0-CSH7 iso-C3H7 iso-C3H7 izo-C3H7 izo-C3H7 izo-C3H7 izo-C3H7 izo-C3H7 izo-C3H7 izo-C3H6 izo-C3H7 izo-C3H6 izo-C3H7 izo-C3H6. H. HHHH COCH3 COCH3 COCH3 COCH3 COCH8 COCH3 COC2H5 COC3H7 (n) COC (CH3) 3 CH3 C2H6 C2H5 C2H5 C2H5 C2H5 iso-C3H7 iso-C3H7 iso-C3H7 iso-C3H7 izo-C3H7 COCH2- C2H5 CH3 C2- C2H5 C25 C2H5 H iso-C8H7 HHHH QH5 C2H5 COCH3 HH COCHs COCHs 10 10 10 3.2 3.2 32 32 32 32 10 32 * 10 32 * 32 32 * 32 32 3.2 * 10 32 * 10 3.2 * 3, 2 10 32 1.0 32 3.2 3.2 3.2 3.2 3.2 32 32 10 3.2 32 * 32 * 32 * 32 32 3.2 32 10 32 * 10 32 3.2 32 * 32 10 32 32 32 32 * 32 32 10 3.2 * 3.2 3.2 1 3.2141 382 1 HHHHHHHHHHHH Cl H Cl 11 2 H Cl FH Cl FH Cl Cl Cl H Cl HH 3 CF3 CF3 CF3 CF3 CF3 CF3 CF3 CF3 C2H5 QH5 C6H5 C2HB C2H5 C2H5 4 HHHHHH C2H5 C2H5 HH C2H5 CH3 C2H5 C2H5 5 C2H5 C2H5 C2H5 iso-C3H7 iso-C3H7 izo-C3H7 C2H5 C2H5 izo-C3H7 izo-C8H7 32H5 ¦ CH3 10 32 3.2 * 3.2 * 32 32 32 32 32 * 10 32 * *) Test compound was as a salt of methanesulfonic acid. The method of the invention is illustrated in the following non-limiting examples. All temperatures are given in degrees Celsius. Example I. 4-Chloro-7-fluoro [1,2,4] triazol [4,3-a] -quinoxaline a) Preparation of 2-chloro-6-fluoro-3- methoxyquinoxaline To the reaction flask which was dried over the flame of a burner and containing a suspension of 52 g (0.24 mol) of 2,3-dichloro-6-fluoroquinoxaline in 500 ml of methanol, the solution was slowly added dropwise under an atmosphere of dry nitrogen at 50 ° C. 6.6 g (0.29 mole) of sodium dissolved in 650 ml of methanol. The resulting reaction mixture is heated completely at 50 ° C overnight (i.e. for about 16 hours) and the resulting clear solution is allowed to stand. cooling to room temperature (about 20 ° C.). The reaction mixture is then concentrated under reduced pressure, the residue obtained is dissolved in chlorophore, washed with water and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, a liquid residue is obtained, which is chromatographed on a 1000 ml silica gel column and then eluted with toluene. From the combined fractions containing only the reaction product, 48.3 g (95%) of pure 2-chloro-6-fluoro-3-methoxyquinoxaline were obtained, mp 93-95 ° C. The mass spectrum contains the following peaks: m / e 212 (parent P ion), m / e 214 (P + 2). b) Preparation of 6-fluoro-2-hydrazine-3-methoxyquinoxaline To a solution containing 47 g (0.22 mol) of 2-chloro-6-fluoro-3-methoxyquinoxaline dissolved in 1000 ml of ethanol is added 27.6 g (0.55 mol) of hydrazine hydrate (26.8 ml). The mixture thus obtained was stirred at room temperature overnight (i.e. at about 20 ° C for about 16 hours). After mixing is complete, 9 ml of hydrazine hydrate are added and the mixture is stirred at room temperature for 4 hours. The precipitate was then filtered off and washed with ethanol, finally obtaining 43.3 g of 20 25 35 45 51 65 (94%) pure 6-fluoro-2-hydrazine-3-methoxyquinoxaline, mp 170-174 ° C, with decomposition. c) Preparation of 7-fluoro-4-methoxy [1,2,4] triazolo [4,3-a] quinoxaline A mixture of 15 g (0.072 mol) of 6-fluoro-2-hydrazine-3-methoxyquinoxaline and 250 ml of triethyl orthoformate are heated with constant stirring in an oil bath at 100 ° C overnight (approximately 16 hours). The resulting mixture is cooled to room temperature, the separated precipitate is filtered off under reduced pressure and washed with ethanol to obtain 11.3 g of pure 7-fluoro-4-methoxy [1,2,4] triazolo [4,3-a ] quinoxalines having a melting point of 245 ° -246 ° C. (decomposition) with a yield of 72%. d) Preparation of 7-fluoro-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline A mixture of 11.3 g (0.52 mol) 7-fluoro-4-methoxy- [1,2 The 4] triazolo [4,3-a] quinoxaline, 115 ml of 1N hydrochloric acid and 345 ml of glacial acetic acid are heated under reflux for 3 hours. The reaction mixture is then cooled to room temperature and poured. The mixture is stirred for 30 minutes, the precipitate is filtered off, washed with water and dried in the air to obtain 8.9 g of pure 7-fluoro-4-hydroxy- [1,2,4] triazolo [ 4,3-a] quinoxaline having a melting point of more than 300 ° C. in a yield of 84%. Mass Spectrum: m / e 204 "(P). E) Preparation of 4-Chloro-7-fluoro [1,2,4] triazol [4,3-a] quinoxaline In a reaction flask dried over a burner flame, under nitrogen atmosphere 8.9 g (0.044 mol) 7-fluoro-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline, 160 ml phosphorus oxychloride and 8.9 ml tri-n- Propylamine. The reaction mixture is refluxed overnight for about 16 hours, cooled to room temperature, and poured into an ice-water mixture while stirring. The resulting aqueous mixture is then stirred at room temperature, the precipitate is filtered, rinsed with cold water, and triturated with ethyl acetate to obtain 7.0 g of pure 4-chloro-13,141,382 14 -7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline at a temperature of m / e 222 (P); m / e 224 (P + 2). Example II. 4-chloro-1-ethyl-7-fluoro [ 1,2,4] - triazolo [4,3-a] quinoxaline a) Preparation of 1-ethyl-7-fluoro-4-methoxy [1,2,4] triazole [4,3-a] quinoxaline A mixture of 15 g (0.07 mol) of 6-fluoro-2-hydrazine-3-methoxyquinoxaline, product prepared as described in example Ib, and 250 ml of triethyl orthopropionate is heated while stirring. in an oil bath at 100 ° C overnight (approximately 16 hours). The resulting mixture is cooled to room temperature (about 20 ° C), the precipitate is filtered off and washed with ethanol to obtain 11.3 g of pure 1-ethyl-7-fluoro-4-methoxy [1,2,4] triazolo [ 4,3-a] quinoxaline, mp 200-202 ° C (with decomposition), yield 64%. b) Preparation of 1-ethyl-7-fluoro-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline. A mixture of 11.3 g (0.046 mol) 1-ethyl-7-fluoro-4- -methoxy [1,2,4] triazolo [4,3-a] quinoxaline, 115 ml of 1N hydrochloric acid and 345 ml of glacial acetic acid are heated to reflux for 3 hours. The reaction mixture is cooled to room temperature and poured into a mixture of ice and water. The whole is stirred for 30 minutes, the precipitate is filtered off, washed with water and dried in air, obtaining 6.6 g of pure 1-ethyl-7- fluoro-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline, mp> 300 ° C, yield 62%. Mass spectrum: m / e 232 (P); m / e 231 (PD. c) Preparation of 4-Chloro-1-ethyl-7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline Place the reaction flask, dried over a burner flame, under a nitrogen atmosphere , 6.6 g (0.028 mol) of 1-ethyl-7-fluoro-4-hydroxy [1,2,4] triazol [4,3-a] quinoxaline, 120 mL of phosphorus oxychloride and 6.6 m l tri-n-propylamine. The reaction mixture was refluxed overnight for about 16 hours, cooled to room temperature, and poured into an ice-water mixture while stirring. The aqueous mixture thus obtained was stirred at room temperature for 30 minutes. minutes, the resulting precipitate is filtered off, washed with cold water and dissolved in ethyl acetate. The organic solution is washed successively with water, a saturated aqueous solution of acidic sodium carbonate and saturated brine, and then dried over anhydrous magnesium sulfate. After the drying agent has been filtered off and the solvent is distilled off under reduced pressure, a beige, solid product is obtained. which, after trituration with diethyl ether, gives 4 g of pure 4-chloro-1-ethyl-7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 203-205 ° C; with the efficiency of 57 # / o. Mass spectrum: m / e 250 (P); m / e 252 (P +2); m / e 249 (P - 1). Example III. 4,7-dichloro [1,2,4] triazolo [4,3-alquinoxaline a) Preparation of 2,3-dihydrocphy-G-chloroquinoxaline Mixture 100 g 0.07 mol) 4-chloro-1,2 -phenylenediamine and 750 ml of diethyl oxalate are heated under reflux overnight for about 16 hours. Then the reaction mixture is cooled to room temperature (about 20 ° C), the precipitate is filtered off, washed with ethanol and air-dried until constant weight to obtain 140 g of pure 2,3-dihydroxy-6-chloroquinoxaline with a melting point above 260 ° C. b) Preparation of 2,3,6-trichloroquinoxaline A mixture of 140 g (0.70 mol) of 2,3-dlhydroxy-6-chloroquinoxaline and 326 ml (3.50 mol) of phosphorus oxychloride was heated overnight (about 16 hours) and poured onto ice. The resulting precipitate is filtered off from the obtained aqueous mixture, washed with water, air-dried and dissolved in chloroform. The organic solution is washed with saturated brine and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, a thick sludge is obtained, from which, after recrystallization from a mixture of chloroform and ethanol, 120 g of pure 2,3,6-trichloroquinoxaline are obtained, m.p. 139-142 ° C, 30 with a capacity of 7 # Vo. Mass spectrum: m / e 232 (P), m / e 234 (P + * 2), m / e 236 (P + 4). c) Preparation of 2,6-dichloro-3-methoxyquinoxaline Solution 1 is added dropwise to a suspension of 11.7 g (0.05 mol) of 2,3,6-trichloroquinoxaline in 140 ml of methanol heated to 50 ° C. 4 g (0.06 mol) of sodium in 140 ml of methanol within 6 hours. The resulting mixture was heated at 50 ° C. overnight (about 16 hours) and 140 mg of sodium dissolved in 20 ml of methanol was added during 1 hour. The mixture is heated at 50 ° C for 2 hours and cooled to room temperature. The mixture is then concentrated under reduced pressure and the residue is dissolved in a mixture of chloroform and water. The organic layer is separated and the aqueous phase is re-extracted with chloroform. The combined organic extracts were washed with fresh portions of water and saturated brine and dried over anhydrous magnesium sulfate. After the drying agent was filtered off and the solvent was distilled off under reduced pressure, the residue was chromatographed v on a silica gel column of 55 250 ml and eluted with toluene. The combined fractions gave 9.8 g of a white solid, pure 2, G-dichloro-3-methylxquinoxaline, mp 92-95 ° C, a yield of 86%. d) Preparation of 6-chloro-2-hydrazine-3-methoxy-quinoxaline A mixture of 4.9 g {0.02 moles) of 2v6-dicnloro-3-methoxyquinoxaline, 2.7 g (0.053 moles) of hydrate hydrate The gins (2.6 ml) and 75 ml of ethanol are stirred at room temperature overnight (ie at 20 ° C. for about 16 hours). The precipitate was then filtered off and washed with ethanol to give 4.4 g of pure 6-chloro-2-hydrazine-3-methoxyquinoxaline, mp 175-179 ° C (decomposition), 98% yield. Mass spectrum: m / e 224 (P); 226 (P + 2). e) Preparation of 7-chloro-4-methoxy [1,2,4] triazolo [4,3-a] quinoxaline A mixture of 1.4 g (0.0062 mol) of 6-chloro-2-hydrazine-3- methoxyquinoxalines and 20 ml of triethyl orthoformate are heated with stirring in an oil bath at 100 ° G overnight (about 16 hours). The resulting mixture is cooled to room temperature, the resulting precipitate is filtered off under reduced pressure and washed with ethanol to obtain 1.0 g of pure 7-chloro-4-methoxy- [1,2,4] triazolo [4,3-a] quinoxalines having a melting point of 250 ° -252 ° C. with a yield of 69%. f) Preparation of 7-chloro-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline A mixture of 3.4 g (0.014 mol) 7-chloro-4-methoxy [1,2, 4] triazolo [4,3-a] quinoxaline, 35 ml of 1N hydrochloric acid and 105 ml of glacial acetic acid are refluxed for 2.5 hours. The reaction mixture is then cooled to room temperature and poured into a mixture of ice and water. The whole is stirred for 20 minutes, the precipitate is filtered off, washed with water and air-dried until constant weight, obtaining 2.6 g of pure 7-chloro-4-hydroxy [1,2,4] triazole [4,3-a] quinoxaline with a melting point above 300 ° C, yield 87%. g) Preparation of 4,7-dichloro [1,2,4] triazolo [4,3-a] quinoxaline A reaction flask dried over a burner flame is placed under a nitrogen atmosphere, 2.6 g (0.012 mol) 7 -chloro-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline, 40 ml of phosphorus oxychloride and 2.6 ml of tri-n-propylamine. The reaction mixture is refluxed overnight for about 16 hours, cooled to room temperature and slowly poured into an ice-water mixture. The resulting aqueous mixture is extracted with ethyl acetate, the extract is washed successively with water, with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, a yellowish solid is obtained as a residue, which is chromatographed on a 200 ml silica gel column using a volumetric mixture of chloroform and methanol as eluerite. 9: 1, the appropriate fractions were combined and concentrated under reduced pressure to give 1.89 g of pure 4,7-dichloro [1,2,4] triazolo [4,3-a] quinoxaline as an orange solid, m.p. 253-256 ° C (with decomposition), yield 66%. Mass spectrum: m / e 238 (P); m / e 240 (P + 2); m / e 242 (P + 4). Example IV. 4,7-dichloro-1-ethyl [1,2,4] triazole [4,3-a] quinoxaline a) Preparation of 7-chloro-1-ethyl-4-methoxy [1,2,4] triazole [4,3-a] quinoxaline 16 A mixture of 5.1 g (0.022 Tnol) of 6-chloro-2-hydrazine-3-methoxyquinoxaline, the product of Example Illd, and 60 ml of triethyl orthopropionate are heated under stirring. in an oil bath at 100 ° C overnight (approximately 16 hours). The mixture is cooled to room temperature (about 20 ° C), the precipitate is filtered off under reduced pressure and washed with diethyl ether to obtain 4.3 g of pure and 7-chloro-1-ethyl-4-methoxy [1,2 4] triazolo [4,3-a] quinoxalines, m.p. 221 ° -223 ° C., yield 75%. . . ". b) Preparation of 7-chloro'-1-ethyl-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline A mixture of 4.3 g (0.0072 mol) of 7-chloro 1-ethyl-4-hydroxy [1,2,4] triazolo [4,3-a] quinoxaline, 40 ml of 1N hydrochloric acid and 60 ml of methanol were refluxed overnight and then cooled to room temperature at room temperature 20. The resulting precipitate is filtered off under reduced pressure and washed with methanol to obtain 3.7 g (94%) of pure 7-chloro-1-ethyl-4-hydroxy [1,2,4] triazole [4,3-a] quinoxaline with a melting point above 300 ° C. 25 c) Preparation of 4,7-dichloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline In dried over a flame Place, under an atmosphere of dry nitrogen, 5.1 g (0.02 mol) of 7-chloro-1-ethyl-4-hydroxy- [1,2,4] triazolo [4,3-a] quinoxaline in the burner torch of the reaction flask. 75 ml of phosphorus oxychloride and 5 ml of tri-n-propylamine The reaction mixture is refluxed overnight for about 16 hours, cooled to this point. room temperature and poured slowly into the ice-water mixture. The resulting aqueous mixture was stirred at room temperature for 15 minutes, the precipitate was filtered off, washed with cold water and air dried until constant weight to obtain 4.2 g of pure 4,7-dichloro-1-ethyl [1 , 2,4] triazolo [4,3-a] ehinoxaline, mp 217-220 ° C (decomposition), yield 79%. Mass spectrum: m / e 266 (P), 268 (P + 2); m / e 265 (P-1). 45 Example V. 4-chloro-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 2,3-dihydroxy-6-methoxyquinoxaline Mixture 20 g (0.114 mol) 4 -methoxy-o-phenylenediamine and 11 g (0.114 mole) of triethylamine in 200 ml of diethyl oxalate are refluxed for about 16 hours. The reaction mixture is then cooled to room temperature (20 ° C) and the product filtered. After washing with ethanol, 14.8 g of pure 2,3-dihydroxy-6-methoxyquinoxaline having a melting point of more than 300 ° C. and a yield of 68% are obtained. Mass spectrum: m / e 192 (P). b) Preparation of 2,3-Dichloro-6-methoxyquinoxaline In a reaction flask dried over the flame of a burner, 14.8 g (0.077 mol) of 2,3-dihydroxy-6-methoxyquinoxaline are placed under an atmosphere of dry nitrogen, 75 ml of phosphorus oxychloride and 15 ml of 65 tri-n-propylamine. The exothermic reaction mixture is stirred at room temperature (20 ° C) for one hour and then refluxed overnight (about 16 hours). The reaction mixture is then reacquired. It is cooled to room temperature and slowly poured into ice-water. The resulting water mixture is stirred at room temperature for 20 minutes, the precipitate is filtered off, washed with water and dissolved in chloroform. This solution is filtered to remove soluble particles and the filtrate is washed successively with water, saturated acid sodium carbonate solution and saturated brine solution. The washed filtrate is concentrated under reduced pressure and the residue is recrystallized from ethanol to give 14.2 g of pure sodium carbonate. 2,3-dichloro-6-methoxyquinoxaline, mp 156-159 ° C, yield 80%. Mass spectrum: m / e 228 (P); m / e 230 (P +2); m / e 232 (P + 4). c) Preparation of 2-chloro-3,6-dimethoxyquinoxaline To a reaction flask dried over a burner flame, containing a suspension of 7.1 g of 2,3-dichloro-6-methoxyquinoxaline in 60 ml of methanol is slowly added under nitrogen atmosphere, a solution of 850 mg of sodium in 80 ml of methanol at 50 ° C. and for 7 hours. The resulting mixture was heated at 50 ° C. overnight and then cooled to room temperature. The reaction mixture becomes concentrated under reduced pressure, the residue is dissolved in chloroform, washed with water, and dried over anhydrous magnesium sulfate. After the drying agent was filtered off and the solvent was distilled off under reduced pressure, the residue was chromatographed on a 400 ml silica gel column and then eluted with toluene. The appropriate fractions were combined and concentrated under reduced pressure to give 6.1 g of pure 2-chloro-3,6-methoxyquinoxaline in the form of a white solid, m.p. 79-81 ° C., yield 88%. • * Analysis result: Calculated for C10H9ClN2O2: ° C 53.47% H 4.04% N 12.47. Found:% C 53.29% H 4.05% N 12.28. d) Preparation of 3,6-dimethyloxy-2-hydroxyquinoxaline A mixture of 5 g (0.022 mol) of 2-chloro-3,6-dimethoxyquinoxaline and 2.8 g (0.056 mol) of hydrazine hydrate (2.7 ml ) in 75 ml of methanol and heated to 50 ° C overnight. An additional 1.0 ml of hydrazine hydrate is then added to the mixture and the mixture is heated at 50 ° C. for 6 hours. Then 1.0 ml of hydrazine hydrate is added again, the whole is heated at 50 ° C overnight and cooled to room temperature. The resulting precipitate is filtered off and washed with ethanol to give 4.1 g of pure 3.6 g. dimethoxy-2-hydrazinoquinoxaline at. mp 128-130 ° C (decomposition), yield 85%. 18 e) Preparation of 4,7-dimethoxy [1,2,4] triazolo [413-a] quinoxaline A mixture of 1.5 g (0.068 mol) of 3,6-dimethoxy-2-hydrazinoquinoxaline and 20 ml of triethyl orthoformate is heated with stirring in an oil bath at 100 ° C overnight (16 hours). The resulting reaction mixture is cooled to room temperature, the precipitate is filtered off under reduced pressure and washed with ethanol 0 to obtain 1.8 g of pure 4 , 7-dimethoxy [l, 4] triazol [4,3-a] quinoxaline, mp 238-240 ° C (decomposition). Mass spectrum: m / e 230 (P); m / e 231 (P + l), m / e 232 (P + 2). f) Preparation of 4-hydroxy-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline. A mixture of 1.6 g (0.0069 mol) 4,7-dimethoxy- [1 The 2,4] triazolo [4,3-a] quinoxaline, 16 ml of 1N hydrochloric acid and 48 ml of glacial acetic acid are heated under reflux for 3 hours. The reaction mixture is then poured over ice and sucks. The product is collected on a filter and washed with diethyl ether to obtain 1.19 g of pure 4-hydroxy-7-methoxy [1,2,4] triazolo [4,3-a] quinoxamine with a melting point above 250 ° C . with an efficiency of 80%. g) Preparation of 4-Chloro-7-methoxy [1,2,4] triazole- [4,3-a] quinoxaline. In a reaction flask dried over the flame of a burner, 1.1 g are placed under an atmosphere of dry nitrogen. (0.0055 mol) 4-hydroxy-7-methoxy [1,2,4] triazole [4,3-a] quinoxaline, 15 ml phosphorus oxychloride and 1.0 ml tri-n-propylammonium. The reaction mixture is refluxed overnight for about 16 hours, cooled to room temperature, and slowly poured into an ice-water mixture. The resulting aqueous mixture is extracted with ethyl acetate, and the extract is washed with water. water and saturated saline successively, and dried over anhydrous magnesium sulfate. After evaporation of the drying agent and distillation of the solvent under reduced pressure, the product obtained is chromatographed on a silica gel column of 150 ml capacity and eluted with a 95: 5 mixture of chloroform and methanol by volume. The appropriate fractions containing the product are 50; is concentrated and concentrated under reduced pressure and the residue is recrystallized from a mixture of chloroform and ethyl ether to give 400 mg of pure 4-chloro-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline at mp 266-268 ° C (decomposition), 55 with a yield of 31%. Mass spectrum: m / e 234 (P), m / e 236 (P + 2). Example VI. 4-Chloro-l-ethyl-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of l-ethyl-4,7-dimethyxy [1,2,4] tria-60 solo- [4,3-a] quinoxaline. A mixture of 4.0 g (0.018 mol) of 3,6-dimethoxy-2-hydrazinoquinoxaline prepared as described in Example Vb and 50 ml of triethyl orthopropionate was heated under stirring in an oil bath at 100 ° C overnight (about 141 382 19 20 16 hours). The resulting reaction mixture is cooled to room temperature (about 20 ° C). The precipitate is filtered off under reduced pressure and washed with ethanol to obtain 3.3 g of pure 4,7-dimethoxy-1-ethyl [1]. 2,4] triazolo [4,3-a] quinoxaldry, m.p. 184-188 ° C., yield 72%. Mass spectrum: m / e 258 (P); m / e 228 (P-30). b) Preparation of 1-ethyl-4-hydroxy-7-methoxy [l32,4] triazolo [4,3-a] quinoxaline. A mixture of 3.3 g (0.013 mol) 4,7-dimethoxy-1-ethyl [1.2 The, 4] triazolo [4,3-a] quinoxaline, 33 ml of 1 N hydrochloric acid and 99 ml of glacial acetic acid are heated under reflux for 2 hours. The reaction mixture is then cooled to room temperature and poured into an ice-water mixture. The mixture was stirred for 20 minutes and extracted with ethyl acetate. The extract was washed with saturated saline solution and dried over anhydrous magnesium sulfate. After the drying agent was filtered off and the solvent was distilled off under reduced pressure, a yellowish solid was obtained. After washing with water and air drying to a constant weight, 1.87 g of pure 1-ethyl-4-hydroxy-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline are obtained, a melting point above 250 ° C., a yield of 67%. c) Preparation of 4-Chloro-1-ethyl-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline In a flask dried over a burner flame is placed under an atmosphere of dry nitrogen, 1.87 g (0.10 0076 mol) 1-ethyl-4-hydroxy-7-methoxy [1.2.41 triazolo [4,3-a] quinoxaline, 25 ml of phosphorus oxychloride and 1.8 ml of tri-n-propylamine. The reaction mixture was refluxed overnight for about 16 hours, cooled to room temperature, and slowly poured into an ice-water mixture. The resulting aqueous mixture was stirred at room temperature for 30 minutes. the precipitate is filtered off, washed with cold water and dissolved in chloroform. The organic solution is washed thoroughly with saturated saline solution and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, a yellow solid is obtained, which is triturated with ethyl ether and filtered to obtain 1.6 g of pure 4-chloro-1-ethyl-7-methdxy [1 , 2,4] triazolo [4,3-a] quinoxaline, mp 173-175 ° C, yield 80%. Mass spectrum: m / e 262 (P); m / e 264 (P + 2); m / e 261 (tM). Example VII. 4-chloro-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 2,3-dihydroxy-6-fluoroquinoxaline Mixture 26.3 g (0.19 mol) 4-fluoro-1-, 2-phenylenediamines [Journal of the American Chemical Solution, vol. 75, p. 1294 (1953)] and 150 ml of diethyl oxalate are refluxed under a nitrogen atmosphere. within 18 hours. Then the reaction mixture is cooled to room temperature (about 20 ° C), the separated precipitate is filtered off, washed four times with 100 ml portions of ethanol and air-dried until constant weight, 19.3 g of pure 2,3-dihydroxy-6-fluoroquinoxalines with a melting point above 300 ° C (US Pat. No. 3,992,378 states that its melting point is 387-390 ° C) in an 80% yield. Mass spectrum: m / e! <180 (P +). b) Preparation of 2,3-Dichloro-6-fluoroquinoxaline A mixture of 19 g (0.105 mol) of 2,3-dihydroxy-6-fluoroquinoxaline and 50 ml of phosphorus oxychloride is refluxed overnight (about 16 hours) , cooled to room temperature and poured onto 200 g of ice, stirring constantly. The resulting precipitate was filtered off and washed several times with water to obtain 28.2 g of 2,3-dichloro-6-fluoroquinoxaline, mp 148-152 ° C. c) Preparation of 2-chloro-6-fluoro-3-hydrazinoquinoxaline To a suspension of 28.2 g (0.105 mol) 2,3-dichloro-6-fluoroquinoxaline in 500 ml of ethanol, 15 ml of ( 0.31 mole) of hydrazine hydrate, the suspension turns dark red. The mixture is then stirred at room temperature under nitrogen for 20 hours. The resulting precipitate is filtered off, washed several times with ethanol and air dried until constant weight is obtained; yielding 20.7 g of pure 2-chloro-6-fluoro-3-hydrazinoquinoxaline, mp 190-192 ° C. (decomposition), 93% yield. d) Preparation of 4-chloro-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline A mixture of 10 g (0.047 mol) 2-chloro-6-fluoro-3- 40 hydrazinoquinoxaline and 80 ml The triethyl orthoformate is heated under nitrogen atmosphere, with stirring, in an oil bath at 100 ° C overnight (about 16 hours). The resulting mixture is cooled to room temperature, the precipitate is filtered off under reduced pressure, washed three times with 50 ml of ethanol and air-dried until constant weight to obtain 9.42 g of pure 4-chloro-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline at 50 mp 310-312 ° C (decomposition) with a yield of 91%. Mass spectrum: m / e 224,223,222 (P +) Example VIII. 4-chloro-1-ethyl-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline 55 Mixture 10.0 g (0.047 mol) 2-chloro-6-fluoro-3-hydrazinoquinoxaline - of the product prepared by the method of Example 7, 95 ml (0.47 mole) of triethyl orthopropionate are heated under nitrogen atmosphere while stirring in an oil bath 60 at 100 ° C overnight (about 16 hours). The resulting mixture is cooled to room temperature (about 20 ° C), the precipitate is filtered off under reduced pressure, washed three times with 50 ml portions of ethanol and dried in air until constant weight, obtaining 7.5 g of pure 4-chloro-1-ethyl-8-fluoro [1,2,4] triazolo- t4,3-a] ch] 'nooxa -ine, m.p. 160—163 ° C (with decomposition), yield 65 ° / o. Mass spectrum: m / e 249, 250, 251, Z52 (P +) Example IX. 4-chloro-8-fluoro-1-trifluoromethyl [1,2,4 itriazo] o {4,3-a] quinoxaline a) Preparation of 8-fluoro-4-hydroxy-1-trifluoromethyl [1,2, 4] triazolo [4,3-a] quinoxaline. A mixture of 12.8 g (0.06 mol) of 2-chloro-6-fluoro-3-hydrazinequinoxaline in 50 ml (0.65 mol) of trifluoroacetic acid is heated in in a dry nitrogen atmosphere at a temperature of 120 ° C. for 24 hours, stirring continuously until a homogeneous solution was obtained. The reaction mixture is then poured into ice-water with continued stirring, stirred for 30 minutes and then filtered. The separated product is washed three times with portions of water and dried under reduced pressure at 80 ° C to obtain 12.58 g of pure 8-fluoro-4-hydroxy-1-trifluoromethyl [1,2,4] triazole [4,3- a] quinoxalines, mp 298-302 ° C, yield 77 ° C / c Mass spectrum: m / e 272 b) Preparation of 4-chloro-8-fluoro-1-trifluoromethyl [1,2,4] triazolo [ 4,3-a] quinoxaline In a three-necked reaction flask dried over a torch flame under an atmosphere of dry nitrogen, 12.5 g (0.046 mol) of 8-fluoro-4-hydroxy-1-trifluoromethyl [1,2, 4] triazolo [4,3-a] quinoxalines, 85 ml phosphorus oxychloride and 17.5 ml tri-n-propylamine. The reaction mixture is refluxed overnight for about 16 hours, cooled to room temperature (about 20 ° C) and slowly poured into 1000 ml of ice water with continued stirring. The resulting water mixture is then stirred. Within 30 minutes at room temperature, it is extracted three times with 3-ml portions of chloroform. The combined organic layers are washed successively with a saturated aqueous solution of acidic sodium carbonate, water and a saturated saline solution and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, 10.47 g of pure 4-chloro-8-fluoro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline are obtained in yellow solid, mp 135-138 ° C, yield 79%. Mass spectrum: m / e 2 & 2/290 (P +) Example X 4-chloro-7,8-difluoro [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 2,3 -dihydroxy-6,7-difluoroquinoxaline A mixture of 11.3 g (0.0784 mol) of 4,5-difluoro-o-phenylenediamine (US Pat. No. 4,264,600) and 80 ml (0.589 The mole of cfetylate is heated under reflux for 4 hours. A thick sediment of the product falls out of the mixture. The reaction mixture is cooled gradually to room temperature (about 20 ° C) overnight, the precipitate is filtered off, washed several times with diethyl ether and dried in air until constant weight, yielding 15.5 g of pure 15 2,3-dihydroxy -6,7-difluoroquinaxaline with a melting point above 310 ° C. Mass spectrum m / e 198 (P +). b) Preparation of 2,3-dichloro-6,7-difluoroquinoxaline A mixture of 15.4 g (0.078 mol) of 2,3-dihydroxy-6,7-difluoroquinoxaline, 39 g (0.187 mol) of phosphorus pentachloride and 20 ml (0.22 mole) of phosphorus oxychloride are refluxed with stirring for 4 hours, while another 20 ml of phosphorus oxychloride are added during this time to facilitate stirring (the mixture is stirred for 30 minutes). the reaction becomes homogeneous). The reaction mixture is then stirred overnight for about 16 hours at room temperature. A pale yellow precipitate forms from the mixture while stirring. The entire mixture was poured into 200 g of ice water with stirring to obtain, after further cooling the mixture, 20.9 g of 2,3-dichloro-6,7-difluoroquinoxaline as a meringue solid, m.p. 162 ° -164 ° C. C (decomposed). Mass spectrum: m / e 238/236/234 (P +). c) Preparation of 2-chloro-6,7-difluoro-3-hydrazinoquinoxaline A mixture of 10 g (0.0426 mol) 2,3-dichloro-6,7-difluoroquinoxaline and 5 ml (0.03 mol) with alcohol The hydrazine in 200 ml of ethanol is stirred at room temperature for 24 hours. A rusty red precipitate falls out of the mixture during this time. The solid suspension is filtered, washed twice with 20 ml of ethanol and air-dried until constant weight to obtain 5.99 g of pure 2-chloro-6,7-difluoro-3-hydrazinoquinoxaline, mp 212- 215 ° C. (decomposition), yield 67%. Mass spectrum: m / e 230 (P), m / e 232 (P +). d) Preparation of 4-chloro-7,8-difluoro [1,2,4] triazol [4,3-a] quinoxaline. Mixture 5.99 g (0.026 mol) 2-chloro-6,7-diflu- oro-3-hydrazinoquinoxaline and 30 ml (0.18 mole) of triethyl orthoformate are heated at 100 ° C. for 24 hours. During this time, a reddish brown precipitate is released from the mixture. The resulting suspension is cooled to room temperature, the resulting precipitate is filtered off. and washed with diethyl ether to obtain 5.15 g of pure 4-chloro-7,8-difluoro [1,2,4] triazolo [4,3-a] quinoxaline at 50, melting point above 210 ° C (decomposition ¬ dem), yield 82 * / «. Mass spectrum: m / e 242/240 Example XI. 4-chloro-6,7-difluoro-1-ethyl- [1,2,4] triazolo [4-3-a] quinoxaline 55 Mixture 7.0 g (0.03 mol) 2-chloro-6.7- Dichloro-3-hydrazinoquinoxaline - the product prepared by the method given in the example "Xc, and 60 ml of triethyl orthopropionate are heated, with stirring, under nitrogen atmosphere, in an oil bath at 100 ° C for 24 hours. The reaction mixture is cooled to room temperature (about 20 ° C), the red precipitate is filtered off under reduced pressure, washed twice with portions of diethyl ether and air-dried until constant weight is obtained, yielding 141 382 23 24 4.15 g of pure 4-chloro-6,7-difluoro-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 195-186 ° C (decomposed), yield 52 %. Example XII. 4,8-dichloro-1-methyl [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 2,6-dichloro-3-hydrazinoquinoxaline Mixture 23 g ( 0.10 mol) 2,3,6-trichloroquinoxaline and 11 g (0.22 mol) of hydrazine hydrate in 500 ml ethanol Stir at room temperature (about 20 ° C) overnight (about 16 hours). The resulting precipitate is filtered off and washed with ethanol to give 22.2 g of pure 2,6-dichloro-3-hydrazine-quinoxaline. a melting point above 250 ° C, 97% efficiency. Mass spectrum: m / e 228 (P). b) Preparation of 4,8-dichloro-1-methyl [1,2,4] triazole [4,3-a] quinoxaline A mixture of 20 g (0.086 mol) 2,6-dichloro-3-hydrazinoquinoxaline and 160 ml (0.87 mol) of triethyl orthoacetate are heated with stirring under an atmosphere of dry nitrogen in an oil bath at 100 ° C for 20 hours to give a yellow suspension. It is cooled to room temperature, the precipitate is filtered off, washed with ethanol and air-dried to constant weight, yielding 10.2 g of pure 4,8-dichloro-1-methyl- [1,2,4] triazolo [4 , 3-a] quinoxaline having a melting point of more than 280 ° C., yield 46%. Mass spectrum: m / e 254/252 (P +) Example XIII. 4,8-dichloro-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 8-chloro-4-hydroxy-1-trifluoromethyl [1,2,4] triazole [4,3-a] quinoxaline In a 500 ml three-necked reaction flask, dried over the flame of a burner, equipped with a mechanical stirrer, a nitrogen tube and reflux coolers, 67 ml (0.87 mole) of acid are placed. trifluoroacetic acid. After stirring, 20 g (0.087 mole) of 2,6-dichloro-3-hydrazinequinoxaline, the product of the preparation of Example XIIa, are added. The reaction mixture is heated in a steam bath for 24 hours, cooled to room temperature (about 20 ° C) and poured into 200 g of ice water. The water mixture is stirred for 30 minutes, the precipitate is filtered off, washed several times with water. and air-dried to a constant weight (requires about 18 hours). 14.3 g of pure 8-chloro-4-hydroxy-1-trifluoromethyl [1,2,4] -triazolo [4,3-a] quinoxaline with a melting point of 253-255 ° C (with decomposition) are obtained. with an efficiency of 57%. Mass spectrum: m / e 290/288 (P +). b) Preparation of 4,8-dichloro-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline In a 250 ml three-necked flask dried over the flame of a burner, equipped with a mechanical stirrer, dropping funnel and reflux coolers , place 14.3 g (0.05 mol) of 8-chloro-4-hydroxy-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline in 100 ml of oxychloride under a blanket of nitrogen. phosphorus. 19 ml (0.10 mol) of tri-n-propylamine are added dropwise to the mixture obtained over 5 minutes. The whole is then heated to reflux for 20 hours, giving a homogeneous, dark red solution. The solution is then cooled to room temperature and poured into 1000 ml of ice water with vigorous stirring. The resulting aqueous mixture is stirred at room temperature for 30 minutes and extracted three times with 500 ml of chloroform each. The combined organic layers are washed successively with water, a saturated aqueous solution of sodium carbonate acid, water and a saturated saline solution, and dried over anhydrous magnesium sulfate. After the drying agent is filtered off and the solvent is distilled off under reduced pressure, 11.4 g of pure 4 are obtained. , 8 dichloro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline as a yellow solid, mp 133-135 ° C, yield 75%. Mass spectrum: m / e 308 (P + 2), m / e 310 (P + 4). 20 Example XIV. 4,8-Dichloro-1-phenyl [1,2,4] triazolo. [4,3-a] quinoxaline In a 250 ml three-necked flask equipped with a mechanical stirrer and reflux condensers, 50.0 g (0.274 mole) of trimethyl orthobenzoate preheated to a temperature of about 70 ° C. After commencing stirring, 10.0 g (0.0437 mole) of 2,6-dichloro-3-hydrazinoquinoxaline prepared as in Example XIIa are added. The reaction mixture is heated to a temperature of about 120 with stirring. ° C within 24 hours, cooled to room temperature (about 20 ° C) and stirred overnight for about 16 hours, forming a yellow slurry. After filtration, the resulting solid was washed twice with 50 ml of ethanol and air-dried until constant weight to obtain 9.8 g of crude 4,8-dichloro-1-phenyl [1,2,4] triazole. [4,3-a] quinoxaline, mp 305-307 ° C, yield 72%. Mass spectrum: m / e 316/314 (P +). Example XV. 2-chloro-3-hydrazinoquinoxaline 2,3-dichloroquinoxaline (33.5 g, 0.168 mol) is mixed with 18.5 g (0.369 mol) of hydrazine hydrate in 500 ml of ethanol at room temperature overnight. (i.e. at a temperature of about 20 ° C for about 16 hours). The resulting thick yellow suspension is filtered and the precipitate is washed with ethanol. After recrystallization from hot methanol, 13.5 g of 2-chloro-3-hydrazinoquinoxaline are obtained, m.p. 181 ° C. (decomposition) and a yield of 41%. Mass spectrum 55: m / e 194 (P). Example XVI. 4-chloro- [1,2,4] triazolo [4,3-a] quinoxaline 9.0 g (0.046 mol) of 2-chloro-3-hydrazinoquinoxaline prepared in Example XV is mixed with every 90 ml of orthoformate of triethyl at 100 ° C. for 1 hour. The whole is cooled to room temperature, the precipitated solid is filtered off, washed with cyclohexane and dried to obtain 8.8 g of 4-chloro [1,2,4] triazolo [4,3-a] quinoxaline. mp 287-290 ° C (decomposition - 45141382 ° C), yield 94%. Mass spectrum: m / e 204 (P). Example XVII. 4-chloro-1-methyl [1,2,4] triazolo [4,3-a] quinoxaline 15.5 g (0.080 mol) of 2-chloro-3-hydrazinoquinoxaline prepared in Example XV is mixed with orthoc with diethyl ethane for 3 hours at 100 ° C. The mixture is then cooled to room temperature, the precipitate is filtered off, washed with ethanol and dried in the air, yielding 11.4 g of 4-chloro-1-methyl [1,2,4] triazolo [4, 3-a] quinoxaline, mp 215-222 ° C, yield 65%. Mass spectrum: m / e 218 (P). Example XVIII. 4-chloro-1-ethyl [1,2,4] triazol [4,3-a] quinoxaiin 4.5 g (0.023 mol) of 2-chloro-3-hydrazinoquinoxaline, prepared in Example XV, is stirred with 50 ml of triethyl orthopropionate at 100 ° C. for one hour. The reaction mixture is cooled to room temperature, the resulting white precipitate is filtered off and washed with cyclohexane, yielding 4.5 g of 4-chloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxalines, mp 158-160 ° C., yield 85%. Mass spectrum: m / e 232 (P). Example XIX. 4-chloro-ln-propyl [1,2,4] triazolo [4,3-a] quinoxaline 3.0 g (0.015 mol) of 2-chloro-T5-hydrazinoquinoxaline prepared in Example XV is mixed with 27 ml of triethyl orthamlanate at 10 ° C for 2 hours. The reaction mixture is cooled to room temperature, the precipitate is filtered off and washed with cyclohexane. The crude precipitate is treated with chloroform and filtered to remove insoluble matter. The chloroform solution is concentrated under reduced pressure to give a precipitate which, after recrystallization from chloroform, yields 1.96 g of 4-chloro-ln-propyl [1,2,4] triazolo [4,3-a] quinoxaline mp 173-175 ° C, yield 53%. Mass spectrum: m / e 246 (P). Example XX. 4-chloro-1-isopropyl [1,2,4] triazolo [4.3la] quinoxaline 4.0 g (0.02 mol) of 2-chloro-3-hydrazinoquinoxaline, prepared in Example XV, is mixed with 15 ml of triethyl orthoisobutyrate at 100 ° C for 3 hours. The solution is cooled to room temperature, the resulting precipitate is filtered off and washed with ethanol. The crude solid was recrystallized from 300 ml of hot ethanol to give 2.06 g of 4-chloro-1-isopropyl [1,2,4] triazolo [4,3-a] quinoxaline, mp 208-210 ° C. with an efficiency of 40%. Mass spectrum: m / e 246 (P). Example XXI. 4-methylamino [1,2,4] triazolo [4,3-a] quinoxaline. Solution 2.0 g {0.01 mol) 4-chloro [1,2,4] triazolo [4,3-a] The quinoxaline prepared in Example XVI is saturated in 30 ml of N, N-dimethylformamide with gaseous monomethylamine and stirred at room temperature for 3 hours. Gaseous monomethylamine is bubbled through the solution again and the mixture is stirred at room temperature for an additional 2 hours. The resulting precipitate is filtered off and washed with N, N-dimethylformamide. After recrystallization from N, N-dimethylformamide, 1.37 g of 4-methylamino- [1,2,4] triazolo [4,3-a] quinoxaline are obtained with a melting point of more than 300 ° C, a yield of 69%. . Mass spectrum: m / e 199 (P). Analysis result: Calculated for C10H9N5.% C 60.29% H 4.55 • / • N 35.15 Found: •% C 59.99 • / • H 4.47% N 35.11. 15 Example XXII. 4-dimethylamino [1,2,4] triazol [4,3-a] quinoxaline Suspension 2.0 g (0.01 mol) 4-chloro [1,2,4] triazol [4,3- a] quinoxaline, prepared in example XVI, in 30 ml of N, N-dimethylformamide, is saturated with dimethylamine gas and stirred at room temperature overnight. The reaction mixture is poured onto ice and the precipitate is filtered off. Recrystallization from ethanol gives 640 mg of 4-dimethylamino [1,24] triazolo [4,3-a] quinoxaline, mp 184-186 ° C, yield: 44%. Mass spectrum: m / e 213 (P) Analysis result: Calculated for CnHnN6.% C 61.96 '% H 5.20% N 32.84 30 Found:% C 62.26% H 5.43% N 32 , 96. Example XXIII. 4-ethylamino [1,2,4] triazol [4,3-a} quinoxaline. Suspension 2.0 g (0.01 mol) 4-chloro [1,2,4] triazolo [4,3- a] quinoxaline prepared in Example XVI is saturated in 30 ml of N, N-dimethylformamide with gaseous ethylamine and stirred at room temperature for 2 hours. Ethylamine gas is then bubbled through the mixture again and stirring continued for 2 hours. The precipitate is filtered off and washed with N, N-dimethylformamide. Recrystallization from methanol gives 680 mg of 4-ethylamino [1,2,4] triazolo [ 4,3-a] quinoxaline, mp 254-256 ° C, yield 32%. Mass spectrum: m / e 213 (P) Analysis result: Calculated for CnHuN6:% C 61.96% H 5.20% N 32.84 Found:% C 61.93% H 5.09% N 32.72 . 50 Example XXIV. 4-diethylamino [1,2,4] triazolo [4,3-a] quinoxaline 4.4 g (0.021 mol) 4-chloro- [1,2,4] triazolo [4,3-a] chi The noxaline prepared in Example 21 is mixed with 6.5 ml (0.063 mole) of diethylamine in 100 ml of 55 N, N-dimethylformamide at room temperature for 2 hours. The reaction mixture is poured into the mixture. ice water; crude precipitate is precipitated, which is then sucked off and washed with water. After recrystallization from isopropanol, 3.36 g of 4-diethylamino [1,2,4] triazo [4,3-a] quinoxaline are obtained, mp 117-119 ° C, yield 66 %. Mass spectrum: m / e 241 (P). Example XXV. 4-di-n-propylamino [1,2,4] - 65 triazolo [4,3-a] quinoxaline 35 40 45 141 382 27 28 15 Solution 2.0 g (0.01 mol) 4-chloro- [l, 2,4] triazolq- [4,3-a] quinoxaline prepared in Example 16 and 3.0 g (0.03 mol) of di-n-propylamine in 50 ml of N, N-dimethylformamide are stirred for 3 hours. days at room temperature. The solution is then poured onto ice, the precipitate formed is filtered off and air-dried. Recrystallization from 250 ml of cyclohexane gives 1.1 g of 4-di-n-propylamino [1,2,4] triazolo [4]. , 3-a] quinoxaline, m.p. 240 ° -242 ° C. with an efficiency of 41%. Mass spectrum: m / e 269 (P) Analysis result: Calculated for C 15 H 19 N 5: ° C 66.89 ° C, 7.11 ° N 26.00 Found:% C 66.78 ° H 6.97 ° / ° N 26.12: Example XXVI. 4-isopropylamino [1,2,4] triazolo [4,3-a] quinoxaline 2.0 g (0.01 mol) 4-chloro [1,2,4] triazolo [4,3-a] quino - 20 xaline prepared in Example XVI and 1.77 g (0.03 mole) of isopropylamine in 30 ml of N, N-dimethylformamide are stirred at room temperature overnight. The resulting dark solution is poured onto ice. The precipitate is filtered off and washed with water. The crude compound is recrystallized from ethanol and twice from isopropyl ether to give 1.2 g of 4-isnpropylamino [1,2,4] triazolo [4,3-a] quinoxaline, mp 133-135 ° C. 30 53%. Mass spectrum: m / e 222 (P). Analysis result: Calculated for C 12 H 18 N 5 • 1/3 H 2 O:% C 61.79 • / • H 5.90 ° / o N 30.02 Found: »• C 61, 51 »/ • H 5.89 • / # N 29.90. 35 Example XXVII. 4-Diethylamino-1-methyl [1,2,4] triazolo [4,3-a] quinoxaline The compound is prepared as in Example XXV using 4-chloro-1-methyl as starting material [1, 2,4] triazolo [4,3-a] quinoxaline (prepared in Example XVII) in place of 4-chloro [1,2,4] triazolo [4,3-a] quinoxaline (prepared in Example XVI) and replacing di-n-propylamine with diethylamine. The obtained crude product was recrystallized from chloroform and then from cyclohexane to give 7.2 g of pure 4-diethylamino-1-methyl [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 123 —125 ° C, with a yield of 54 ° C. Example XXVIII. 4-Amino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline Via a solution of 1.2 g (0.005 mol) 4-chloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline prepared in Example 18, ammonia gas is bubbled into 20 ml of N, N-dimethylformamide at 0 ° C. for 2 minutes. The solution is stirred at 0 ° for 30 minutes and then at room temperature for one hour. The reaction mixtures are then poured onto ice and stirred for 60 minutes. The resulting precipitate is filtered off, washed with water and air dried. After recrystallization from ethanol, 220 mg of pure 4-amino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline are obtained with a melting point of 284 ° -288 ° C, the yield is 22%. Mass spectrum: m / e 213 (P). Analysis result: Calculated for CnHnN5. 1/6 H2O:% C 61.10% H 5.28% N 32.39 Found: • C 61.36 • / • H 5.14 • / § N 31.96 .. Example XXIX. 4-methylamino-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline Through a solution of 1.2 g (0.005 mol) 4-chloro-1-ethyl- [1,2,4] gaseous methylamine is bubbled into 50 ml of N, N-dimethylformamide in 50 ml of N, N-dimethylformamide for 2 minutes. Triazolo [4,3-a] quinoxaline prepared in Example 18 is bubbled into the reaction mixture at 0 ° C. within 30 minutes, then at room temperature for 2 hours, poured onto ice and stirred for another 20 minutes. The precipitate was filtered off, washed with water and air dried. After recrystallization from ethanol, 1.0 g of 4-methylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline were obtained, mp 271 ° -273 ° C., yield 88%. Mass spectrum: m / e 227 (P). Analysis result: Calculated for Ci2Hi8N5 • 1/8 H2O:% C 62.80 • / • H 5.82 • / • N 30.51 Found:% C 62.72 • • H 5.86% N 30.62. Example XXX. 4-dimethylamino-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline 1.2 g (0.005 mol) 4-chloro-1-ethyl [1,2,4] triazolo [4 , 3-a] quinoxaline prepared in Example 18 and 676 mg (0.015 mol) of anhydrous dimethylamine in 50 ml of N, N-dimethylformamide are stirred at 0 ° C for 30 minutes and at room temperature for 2 hours. The reaction mixture is then poured onto ice and stirred for 20 minutes. The resulting precipitate is filtered off, washed with water and dried in air. Recrystallization from chloroform and a mixture of chloroform and cyclohexane gives 510 mg of 4-dimethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline mp 155 ° -158 ° C. with a yield of 42%. Mass spectrum: m / e 241 Analysis result: Calculated for C 18 H 15 N 5:% C 64.71. • / • H 6.27% N 29.02 Found:% C 64.69% H 6.27%. N 29.32. Example XXXI. 1-ethyl-4-ethylamino [1,2,4] triazolo {4,3-] quinoxaline. Via a solution of 1.2 g (0.005 mol) 4-chloro-1-ethyl [1,2,4] triazolo [ 4,3-a] quinoxaline, prepared in Example 18, in 50 ml of N, N-dimethylformamide is bubbled at 0 ° C. for about 2 minutes monoethylamine. The clear solution was stirred at 0 ° C for 30 minutes and at room temperature for 2 hours. Then the reaction mixture is poured onto ice, the precipitate is filtered off, washed with water and dried in air. After recrystallization from ethanol, 1/0 g of pure 1-ethyl-4-ethylamino [1,2,4] triazole is obtained. {4,3-a] ohinoxaline in the form of a white solid with a melting point of 235-238 ° C, yield 83f / t. Mass spectrum: m / e 241 (P). 29 141 3S2 30 Result Analyzes: Calculated for CjaHisN *: / · C 64.71 · / · H 6.27 · / # N 29.02 Found: Vo C 64.57. Example XXXII. 4-Diethylamino-1-ethyl [1,2,4] triazolo [4,3-alchmoxaline. The title compound was prepared as in Example XXV using 4-chloro-1-ethyl [1,2,4] as a starting compound. } triazolo [4,3-a] quinoxaline prepared in Example XVIII in place of 4-chloro-II. 4] triazo.lo [4,3-a} quinoxaline, prepared in Example XVI, and replacing the di-n- propylamine diethylamine. After recrystallization of the crude product from cyclohexane, 3.54 g of pure 4-diethylamino-1-ethyl [1,4] triazolo {4,3-a] quinoxaline are obtained in the form of a white solid, mp 9% 100 ° C, an efficiency of 69%. Mass spectrum: m / e 269 (P). Example XXXIII. 4-isopropylamino-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline To a solution of 2.3 g (0.01 mol) 4-chloro-1-ethyl- [1,2,4 ] trtazolo [4,3-a} quinoxaline prepared in Example 18 in 30 ml of N, N-dimethylformamide are added 1.77 g <0.03 mol) isopropylamine. A precipitate was formed within 30 minutes. The reaction mixture was then stirred overnight at room temperature. The resulting precipitate is filtered off and washed with N, N-dimethylformamide. After recrystallization from ethajiol, 1.6 g of 4-isopropylamino-1-ethyl [1,24] triazolo [4,3-a] quincksaline are obtained, mp 222-224 ° C, yield «3 ° / *. Mass spectrum: m / e 255 (P). Analysis result: Calculated for Ci4HiTN5: o C 65.06 * / o H 6.71 * / o N 27.43 Found: • / • C 65.32 * / • H 6.76% N 27.25. Example XXXIV. 4-ethylammo-1-isopropyl- [1,2,4] triazolo [4,3-a] quinoxaline Suspension 1.0 g (0.004 mol) 4-chloro-1-isopropyl [1,2,4] triazole [4,3-a] quinoxaline, prepared in Example XX, is saturated in 15 ml of N, N-dimethylformamide with ethylamine gas and stirred at room temperature for 4 hours. The resulting precipitate is filtered off and washed with N, N-dimethylformamide to give 229 mg of 4-ethylamino-1-isopropyl [1,2,4] triazolo [4,3-a] quinoxaline with a temperature of 200-211 ° C. C, with an efficiency of 22 ° / ». Mass spectrum: m / e 255 (P). The slurry is also poured onto ice, the precipitate is filtered off, washed with water and crystallized from methanol * and then from isopropanol, yielding another 200 mg (yield 20 * / *) of pure 4-ethyl - amino-1-isopropyl [1,2,4] triazolo [4,3-a] <5hinoxalines with a melting point of 210-211 ° C. Analytical result: Ofc & iezcKio for Ci4HiTN?: * / Ziaaleziono- • / • C 65.53 ft / o H 6.58 • / # N 27.29. 4-diethioamino-1-isopropyl- [1,2,4] triazolo {4) 3-alquinoxaline 1.0 g (0% 4 mol) 4-.chloK-1-isopropylethyl, 2,4fferiazo [43- " the alchiaoxalyl as prepared in Example XX and 900 mg (0-12 mol) of diethylamine in 15 ml of N, N-diethylformamide are stirred at room temperature for 4 hours. The reaction mixture is poured onto ice, the precipitate is filtered off, washed with water, placed on a 175 ml silica gel column and washed with chloroform. The solvent is distilled off under reduced pressure to obtain 850 mg of pure 4-diethylamino. -1-isopropyl [1,2,4] triazolo [4,3-a] quinoxaline as a white solid, mp 93-95 ° C, 75% yield. Mass spectrum: m / e 283 (P). 100 mg of the pure product is then distilled at a pressure of 13.3 Pa, N at a temperature of 140-150 ° C, obtaining a sample for analysis with a mass of 80 mg and a melting point of 94-96 ° C. Analysis result: Calculated for C16H2iN6: ° / o C 67.82 o H 7.47 o N 24.71 Found o C 67.56 o H 7.20 o N 24.50 Example XXXVI. 4-diethylamino-ln-propyl- [1,2,4] triazolo [4,3-a] quinoxaline 1.23 g (0.005 mol) 4-chloro-ln-propyl [1,2,4] triazolo [ 4,3-a] quinoxaline prepared in Example 19, and 1.1 g (0.015 mol) of diethylamine in 15 ml of N, N-dimethylformamide are stirred at room temperature for 2 hours. The reaction mixture is then poured onto ice, the precipitate is filtered off, washed with water and air dried. After recrystallization twice from a mixture of ethanol and water, 1.1 g of pure 4-diethylamino-ln-propyl [1,2,4] triazolo [4,3-a] quinoxaline are obtained, m.p. 92/94 ° C. C, yield 78 gg. Analytical result: Calculated for C 16 H "and N 6 -I / 8 H 2 O: • / o C 67.28 • / • H 7.50 • / • N 24.52 Found: • / • € 67.38 % H 7.45 • / # N 24.73 Example XXXVII. 8-chloro-4-diethroamino-1-40-ethyl [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 4,8-dichloro-1-ethyl [1,2,4] triazole [4,3-a] quinoxaline 1.0 g (0.0044 mol) of 2,6-dichloro-3-hydrazinoquinoxaline prepared according to Example XIIa is refluxed with 15 ml of triethyl orthopropionate in for 4 hours and cool to room temperature. The resulting precipitate is filtered off, washed with cyclohexane and air dried to give 730 g of 4,8-dichloro-1-ethyl [1,2,4] triazolo [4, Of 3-a] quinoxalines having a melting point above 250 ° C. in a yield of 62%. Mass spectrum: m / e 266 (P); m / e 268 (P + 2), 55 b) Preparation of 8-chloro-4-diethylamino-l- ethyl- [1,2,4] triazolo [4,3-a] quinoxaline 7.4 g (0.028 mol! 4,8-dichloro-1-ethylthi, 2r4] triazol [4,3-a] quinoxaline and 6 g (0.082 mol) of diethylamine in 150 ml of N, N-dimethylformamide are stirred at room temperature for 4 hours. The reaction mixture is filtered and the filtrate is poured onto ice. The precipitate thus obtained is filtered off and treated with chloroform. The organic layer is dried over anhydrous magnesium sulfate, filtered and the solvent is distilled off under reduced pressure, 141 382 31 32 to give white After recrystallization from a mixture of ethyl ether and petroleum ether, 1.6 g of pure 8-chloro-4-diethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline are obtained. mp 105-108 ° C (with decomposition) Mass spectrum: m / e 303 (P), m / e 305 (P + 2). Analysis result: Calculated for C15H18ClN5: • / o C 59.30® (o H 5.97 °) o N 23.05 Found:% C 58.92 ° (o H 5.85 °) o N 22.81. Example XXXVIII. 7.8-diethyl orb-4-diethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 2,6,7-trichloro-3-hydrazinequinoxaline 4.4 g (0.016 mol ) 2,3,6,7-tetrachloroquinoxaline and 1.76 g (0.035 mol) of hydrazine hydrate in 60 ml of ethanol are stirred overnight at room temperature. The thick suspension is sipped and washed with ethanol to obtain 4.9 g of crude 2,6,7-trichloro-3-hydrazinequinoxaline with a melting point below 260 ° C. Mass spectrum: 262 (P + 2). b) Preparation of 4,7,8-trichloro-1-ethyl [1,2,4] triazol [4,3-a] quinoxaline 4.9 g <0.018 mole) of 2,6,7-trichloro-3-hydrazinoquinoxaline in 50 ml of triethyl orthopropionate is heated at 100 ° C. for 2 hours. The resulting precipitate is filtered off at room temperature and washed with cyclohexane. After recrystallization twice from a solvent mixture of chloroform and cyclohexane, 2.9 g of pure 1,2,4-trichloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline are obtained in a pink solid with a melting point of 198-201 ° C., with a yield of 54%. Mass spectrum: m / e 300 (P); m / e 302 (P + 2); m / e 304 (P + 4); m / e 306 (P + 6). c) Preparation of 7,8-dichloro-4-diethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline 2.9 g (0.0096 mol) 4,7,8- trichloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline and 2.1 g (0.0388 mol) diethylamine in 50 ml of N, N-dimethylformamide are stirred at room temperature in 2 hours. The reaction mixture was then poured onto ice and stirred for 15 minutes. The resulting precipitate was filtered off, washed with water and air dried. After recrystallization three times from isopropanol, 500 mg of pure 7.8-rdi-chloro-4-diethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline are obtained, m.p. 147-149 ° C from yield 16%. Mass spectrum: m / e 337 (P); m / e 339 (P + 2) Analysis result: Calculated for C15H17Cl2N5: ° C 53.26 ° H 5.07 • / N 20.70 Found: • C 53.05% H 5.15% N 20.75 Example XXXIX. 4-diethylamino-1-ethyl-8-methoxy [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 2-chloro-3-hydrazine-6-methoxyquinoxaline 4.2 g (0.018 mol) 2,3-dichloro-6-methoxyquinoxaline prepared according to example Vb and 2.7 ml of hydrazine hydrate in 100 ml of ethanol are refluxed for 4 hours and then stirred at a temperature of 10 minutes. 20 25 peace round overnight. The precipitate was filtered off and washed with ethanol to obtain 3.9 g of 2-chloro-3-hydrazine-6-methoxyquinoxaline, mp less than 250 ° C., 97% yield. Mass spectrum: m / e 224 (P); m / e 226 (P + 2). b) Preparation of 4-chloro-1-ethyl-8-methoxy [1,2,4] - triazolo [4,3-a] quinoxaline ...... 1.5 g (0.0058 mol) 2-chlorine The -3-hydrazine-6-methoxyquinoxaline and 25 ml of triethyl orthopropionate are heated at 100 ° C. for 4 hours and then stirred at room temperature for 60 hours. The precipitate is filtered off and washed with ethanol. After recrystallization from ethanol, 530 mg of pure 4-chloro-1-ethyl-8-methoxy [1,2,4] triazolo [4,3-a] quinoxaline are obtained, mp 196-198 ° C (decomposition) , with an efficiency of 35 ° / &. Mass spectrum: m / e 262 (P); m / e 264 c) Preparation of 4-diethylamino-1-ethyl-8-methoxy- [1,2,4] triazolo [4,3-a] quinoxaline 520 mg (0.002 mol) 4-chloro-1-ethyl-8 -methoxy- [1,2,4] triazolo [4,3-a] quinoxaline and 573 mg (0.008 mol) of diethylamine in 10 ml of N, N-dimethylformamide was stirred at room temperature overnight. The reaction mixture was poured out overnight. on ice and the resulting precipitate is filtered off, washed with water and air dried. After recrystallization from 3Q ethyl ether and petroleum ether, 140 mg of pure 4-diethylamino-1-ethyl-8-methoxy [1,2,4] triazolo {4,3-a] -quinoxaline are obtained, m.p. 135-138 ° C. , with the efficiency of 23%. Mass spectrum: m / e 299 (P). Analysis result: 35 Calculated for C16H2iN50. 1/8 H20: '»/ § C 63/71 ° / o H 7.10%. N 23.22 Found: • / # C 63.63% H 6.88 • / • N 23.37. Example XL. 4-Diethylamino-1-phenyl [1,2,4] triazolo [4,3-a] quinoxaline 40 a) Preparation of 4-chloro-1-phenyl [1,2,4] triazolo [4,3-a ] quinoxaline 2.2 g (0.011 mol) of 2-chloro-3-hydrazinoquinoxaline are mixed with 6 ml of triethyl orthobenzoate and heated at 100 ° C for 30 minutes. After cooling the orange mixture to room temperature, ethanol is added. The precipitate formed is filtered to obtain 2.1 g of a crude product which is further purified by trituration with warm methanol, filtered and air dried to give 1.58 g of pure 4-chloro-1 phenyl- [1,2,4] triazolo [4,3-a] quinoxaline in the form of an orange solid with a yield of 5%. b) Preparation of 4-diethylamino-1-phenyl [1,2,4] triazolo [4,3-a] quinoxaline 55 To 1.58 g (0.00563 mol) 4-chloro-1-phenyl [1, 2,4] - triazolo [4,3-a] quinoxaline dissolved in 15 ml of N, N-dimethylformamide, 1.738 g of diethylamine are added. The mixture was stirred overnight at room temperature. The precipitate is filtered off, washed with N, N-dimethylformamide and twice, recrystallized from a 3: 1 by volume mixture of hexane and ethyl acetate to give 555 mg of pure 4-diethylamine-1-phenyl [1,2,4] triazolo [4 , 3-a] - quinoxalines in the form of white needles, m.p. 166-168 ° C. 33 141 382 34 Analysis result: Calculated for C 19 H 19 N 6:% C 71.60% H 5.99% N 22.06 Found :% C 71.86% H 5.86% N 22.09 Example XLI. 4-diethylamino-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline a) Preparation of 4-hydroxy-1,3-trifluoromethyl- [1,2,4] triazolo [4,3-a ] quinoxaline. To 22.8 g (0.20 mole) of cold trifluoroacetic acid (15.4 ml) placed in a flask dried over a burner in ice, is added under an atmosphere of dry nitrogen while stirring continuously, 3.89 g (0.02 mole) of 2-chloro-3-hydrazinoquinoxaline prepared in Example 15. The reaction mixture is heated to 100 ° C. for 3 hours and poured onto ice. The resulting precipitate is filtered off under reduced pressure, washed with water and dried in air until a constant mass is obtained. 3.0 g of pure 4-hydroxy-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline with a melting point above 300 ° C and a yield of 60% are obtained. Mass spectrum; m / e 254 (P). b) Preparation of 4-chloro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline. In a flask dried over the flame of the burner, 3.0 g (0.0118 moles) are placed under an atmosphere of dry nitrogen. ) 4-hydroxy-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline, 30 ml of phosphorus oxychloride and 2.38 g (0.0236 mol) of triethylamine (3.3 ml). The reaction mixture is then heated to 100 ° C. for about 16 hours (ie, overnight). The reaction mixture was cooled to room temperature, concentrated under reduced pressure, a mixture of ice, water and ethanol was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solvent was distilled off under reduced pressure, to leave a residue which was dissolved in hot chloroform and filtered. The slurry is left to stand overnight and sucked again. The filtrate thus obtained is concentrated under reduced pressure to obtain 1.4 g of 4-chloro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline as a brown solid. c) Preparation of 4-diethylamino-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline. A mixture of 700 mg (0.0025 mol) 4-chloro-1-trifluoromethyl [1,2, 4] triazolo [4,3-a] quinoxaline prepared as described above and 560 mg (0.0075 mol) of diethylamine (0.8 ml) in 10 ml of N, N-dimethylformamide are stirred at room temperature at overnight and poured onto ice. The resulting mixture is filtered, washed with water and dissolved in ethyl acetate. The organic solution is washed with a saturated saline solution and dried over anhydrous magnesium sulfate. After the drying agent is filtered off and the solvent is distilled off under reduced pressure, a light yellow solid is obtained, from which pure 4-diethylamino-1-trifluoromethyl is obtained after recrystallization from ethyl ether. [1,2,4] triazol [4,3-a] quinoxaline. The melting point of the first batch is 155-157 ° C, and its weight is 260 mg (yield 34%). The yield of the second batch is 27% - 170 mg of the product with a melting point of 153-156 ° C are obtained. Analytical result: Calculated for C14H14F8N5:% C 54.37% H 4.56 ° / o N 22.64 Found: % C 54.08% H 4.47% N 23.32. 10 Example XLII. 4-isopropylamino-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline Mixture 700 mg (0.0025 mol) 4-chloro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline prepared in Example XLI b and 443 mg (0.0075 mol) isopropylamine (0.64 ml) in 10. ml of N, N-dimethylformamide is stirred at room temperature overnight and poured onto ice. The mixture thus obtained is filtered, washed with water and dissolved in diethyl ether. The ethereal solution was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, a white powder is obtained, from which 550 mg of pure 4-isopropylamino-1-trifluoromethyl [1,2,4] triazole are obtained after recrystallization from ethyl ether. [4,3-a] quinoxaline, mp 185-187 ° C., yield 74%. Analytical result: Calculated for C18H12F8N5:% C 52.88% H 4.10% N 23.72 Found:% C 52.73% H 4.00% N 23.67. Example XLIII. 1-ethyl-4- (N-ethylacetylamino) [1,2,4] triazolo [4,3-a] quinoxaline Mixture 241 mg (0.001 mol) 1-ethyl-4-ethylamino [1,2 , 4] triazolo [4,3-a] quinoxaline, prepared in Example XXXI, and 2.5 g (0.025 mole) of acetic anhydride (2.5 ml) are placed in a flask dried over a flame and heated in at boiling point (140 ° C) under reflux under an atmosphere of dry nitrogen for 3 hours, then cooled to room temperature. A precipitate is precipitated on cooling. 45 Everything is poured into water and extracted with chloroform. The combined organic layers are washed with water and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure 50, a solid is obtained, from which, after crystallization from a mixture of chloroform and ethyl ether, 160 mg of 1-ethyl-4- (N-ethylacetylamino) is obtained - [1 , 2,4] triazolo [4,3-a] quinoxaline, mp 185-187 ° C, yield 57%. Analysis result: Calculated for C 15 H 17 N 50:% C 63.59% H 6.05% N 24.72 Found:% C 63.17% H 6.05% N 24.39. Example XLIV. 4-acetylamino-1-ethyl [1,2,4] - 60 triazolo [4,3-a] quinoxaline Mixture 533 mg (0.0025 mol) 4-amino-1-ethyl- [1,2,4] triazole [4,3-a] quinoxaline prepared in Example XXVIII and 1.0 g (0.01 mol) of acetic anhydride (1.0 ml) in 20 ml of methylene chloride are heated under reflux. This CZ 35 is refluxed overnight (about 16 hours) and then allowed to cool to room temperature. The obtained clear solution is concentrated under reduced pressure to give a white solid, which, after recrystallization from a mixture of chloroform and ethyl ether, yields 520 mg of pure 4-acetylamino-1-ethyl [1,2,4] triazolc- [4 , 3-a] quinoxaline, mp 192-195 ° C, 82% yield. Analytical result: Calculated for C 18 H 18 N 50: ° C 61.16 Vo H 5.13 ° N 27.43 Found:% C 60.90. "(H 5.26 °) N 27.66. Example XLV.4-diacetylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinixaline Mixture 5.5 g (0.10 0258 mol) 4-amino-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, prepared in Example XXVIII, and 25 g (0.25 mol) acetic anhydride (25 ml) in 60 ml pyridine containing 100 mg of p-dimethylaminopyridine was stirred at room temperature overnight (approximately 18 hours). - The resulting slurry is filtered to remove insoluble particles and the resulting orange-red filtrate is distilled off under reduced pressure, leaving a dark, pliable residue. When water is added, pinkish-white crystals fall out and drain under reduced pressure washed with plenty of water and dried under reduced pressure at 50 ° C to obtain 2.9 g of 4-diacetylcamino-1-ethyl [1,2,2] triazolo [4,3-a] quinoxaline, m.p. 157-159 ° C, yield 38%. After recrystallization from a mixture of ethyl acetate and ethyl ether, an analytically pure sample is obtained, m.p. 158-160 ° C. The pure product was then examined by mass spectroscopy and nuclear magnetic resonance. Mass spectrum: m / e 297 (P) Analysis result: Calculated for C15H15N5O2: ° C 60.59 ° C 5.09 ° N 23.56 Found: ° C 60.33 ° C o H 5.09 »/ o N 23.41. Pr class XLVI. The following 4-amino- [1,2,4] triazolo [4,3-a] quinoxaline derivatives are obtained by following the recipes of the above examples: 7,8-dibromo-4- diethylamino [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 199-201 ° C; 8-chloro-4-isopropylamino [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 177-181 ° C; 4-ethylamino-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline, mp 223-225 ° C; 1-ethyl-4-ethylamino-8-methoxy [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 234-237 ° C; 4-diethylamino-8-methoxy [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 124-126 ° C; 8-chloro-1-ethyl-4-isopropylamino [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 189-191 ° C; 4- (N-piperazine) - [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 160-162 ° C; 8-chloro-4- (N-piperazine) - [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 253-256 ° C; 8-chloro-36 10 15 20 25 30 35 45 50 55 60 ro-4- (N-isopropylacetylamino) - [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 148-151 ° C ; 4-acetylamino-8-chloro-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 203-205 ° C; 8-chloro-1-ethyl-4- (N-isopropylacetylamino) - [1,2,4] -triazolo [4,3-a] quinoxaline, mp 155-158 ° C; 7,8-dichloro-4- (N-isopropylacetylamino) - [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 207-210 ° C .; 4-amino-7,8-dichloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline, melting point greater than 260 ° C; 4-amino-8-chloro-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 248 ° -253 ° C .; 4-acetylamino-7,8-dichloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline, mp 230-232 ° C; 8-fluoro-4-isopropylamino- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 215-217 ° C; 4-ethylamino-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 239 ° -242 ° C .; 1-ethyl-8-fluoro-4-isopropylamino- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 209-212 ° C; 7,8-difluoro-4-isopropylamino- [1,2,4] triazolo [4,3-a] quinoxaline, mp 218-221 ° C; 1-ethyl-4-ethylamino-8-fluoro [1,2,4] triazolo {4,3-a] quinoxaline, m.p. 231-233 ° C; 7,8-difluoro-4-ethylamino [1,2,4] triazolo [4,3-a] quinoxaline, mp 208-211 ° C; 4-diethylamino-8-fluoro- [1,2,4] triazolo [4,3-a] quinoxaline, mp 151-153 ° C; 4-diethylamino-1-ethyl-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline, mp 94-97 ° C; 7-chloro-4-dimethylamino-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 214-217 ° C; 7-chloro-4-diethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline rnethanesulfonate, m.p. 172-175 ° C; 7,8-dichloro-1-ethyl-4- (N-piperazine) - [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 252-255 ° C; 7,8-dichloro-4-dimethylamino-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 168-171 ° C; 7,8-dichloro-4-dimethylamino-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 216-219 ° C; 4-acetylamino-1-ethyl-8-β luoro - [1,2,4] triazolo [4,3-a] quinoxaline, mp 203-205 ° C; 4-Amino-7- chloro-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 240-243 ° C; 7-chloro-1-ethyl-4-ethylamino- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 187-189 ° C; 7-chloro-4-diethylamino- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 205-207 ° C; 4-diethylamino-7,8-difluoro- [1,2,4] triazolo [4,3-a] quinoxa.line methanesulfonate, m.p. 220 ° -223 ° C .; 4-acetylamino-7-chloro-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 210-212 ° C; 8-Chloro-1-ethyl-4-ethylamino- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 235-238 ° C; 4-amino-7-chloro [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 279-282 ° C; 4-amino-8-chloro-1-methyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 213-215 ° C; 8-Chloro-4-isopropylamino-1-trifluoromethyl- [1,2,4] triazolo [4,3-aj-37 quinoxaline methanesulfonate, m.p. 183-185 ° C; 8-chloro-4-diethylamino-1-methyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 172-175 ° C; 4-diacetylamino- [1,2,4] -triazolo [4,3-a] quinoxaline, m.p. 211-214 ° C; 4-diacetylamino-8-chloro- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 208-210 ° C; 8-chloro-4-isopropylamino-1-methyl [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 206-208 ° C; 4-acetylamino-1- methyl-8-chloro [1,2,4] triazolo [4,3-a] quinoxaline, mp 262 ° -264 ° C; 8-chloro-l-ethyl-4-trimethylacetylamino [l, 2,4] triazolo [4,3-a] quinoxaline, mp 211-213 ° C; 7,8-difluoro-1-ethyl-4-isopropylamino [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 151-152 ° C; 4-n-butyrylamino-8-chloro-1-ethyl [1,2,4] triazolo [4,3-a] quinoxaline, mp 185-187 ° C; 8-chloro-4-dimethylamino-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline hydrate, m.p. 135-136 ° C; 4-amino-8-chloro-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 259 ° -261 ° C .; 4-Ethylamino-8-fluoro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 180-183 ° C; 8-fluoro-4-isopropylamino-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 185-188 ° C; 4-diethylamino-7,8-difluoro-1-ethyl- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 109-111 ° C; 1-Ethyl-4-ethylamino-7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 215-219 ° C; 4-Amino-7-methoxy- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 262 °. 264 ° C; 8-chloro-4-isopropylamino-1-phenyl [1,2,4] triazolo [4,3-a] quinoxaline, mp 183-186 ° C; 8-chloro-4-ethylamino-1-phenyl [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 254 ° -256 ° C .; 7-fluoro-4-isopropylamino [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 214-216 ° C; 1-ethylamino-7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 216-218 ° C; 1-diethylamino-8-fluoro-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 146-149 ° C; 7,8-dichloro-1-ethyl-4-isopropylamino [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 197-198 ° C; 8-chloro-4-diethylamino--1-phenyl [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 194 ° -195 ° C .; 4-acetylamino-1-ethyl-7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline, mp 273 ° -275 ° C .; 4-acetylamino-8-chloro-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 215-216 ° C; 4-amino-8-chloro-1-phenyl- [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 273 ° -275 ° C .; 8-chloro-4-ethylamino-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 228-230 ° C; 1-ethyl-7- fluoro-4-isopropylamino- [1,2,4] -triazolo [4,3-a] quinoxaline methanesulfonate, mp 178-181 ° C; 4-amino-8-fluoro-1-trifluoromethyl [1,2,4] triazolo [4,3-a] quinoxaline hydrate, m.p. L 382 38 260-263 ° C; 8-chloro-1-ethyl-4R-phenylisopropylamino [1,2,4] triazolo [4,3-a] quinoxaline, mp 155-157 ° C; 4-amino-1-ethyl-7- fluoro [1,2,4] triazolo [4,3-a] quinoxaline, mp 285-289 ° C; 4-Amino-l-ethyl-7-methoxy [l, 2,4] triazolo [4,3-a] quinoxalyri methanesulfonate, mp 255-258 ° C; 4-acetylamino-8-fluoro-1-trifluoromethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 217-219 ° C; and 4-acetylamino-1-ethyl-7-methoxy [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 202-205 ° C; 8-chloro-1-ethyl-4S-phenylisopropylamino- [1,2,4] triazolo [4,3-a] quinoxaline, mp 156-1-7 ° C; 4-acetylamino-8-fluoro [1,2,4] - β triazolo [4,3-a] quinoxaline, m.p. 240 ° -242 ° C; 4-acetylamino- [1,2,4] triazolo [4,3-a] quinoxaline, m.p. 269-272 ° C; 4-amino-7-fluoro [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, m.p. 246 ° -248 ° C; 4-Amino-8-fluoro [1,2,4] triazolo [4,3-a] quinoxaline methanesulfonate, mp 176-178 ° C; 4-acetylamino-7-fluoro {1,2,4] triazolo [4,3-a] quinoxaline, m.p. 290-292 ° C; -8-chloro-4-isopropylamino-1, pentafluoroethyl- [1,2,4] triazolo [4,3-a] quinoxaline, mp 171-174 ° C. Example XLVII. 8-chloro-1-ethyl-4-propionylamino [1,2,4] triazolo [4,3-a] quinoxaline. Mixture 1.25 g (0.005 mol) 4-aminoT8-chloro-30 * 1-ethyl [ 1,2,4] triazolo [4,3-a] quinoxaline, mp 248-253 ° C, one of the products of the previous example, and 15 ml of propionic anhydride are refluxed under reflux. overnight for about 16 hours, then it is cooled to room temperature (about 20 ° C). The obtained reaction mixture is filtered and the precipitate separated is dissolved in chloroform. The organic solution is filtered, washed successively with water, a saturated aqueous solution sodium carbonate acid and saturated saline solution and dried over anhydrous magnesium sulfate. After filtering off the drying agent and distilling off the solvent under reduced pressure, the residue obtained is chromatographed on a silica gel column of 150 ml capacity and eluted with a 95: 5 mixture of chloroform and methanol by volume. containing the product are combined and concentrated under reduced pressure to obtain a crystalline residue which, after recrystallization from a mixture of chloroform and ethyl ether, yields 540 mg of pure 8-chloro-1-ethyl-4-propionylamino [1,2,4 ] triazolo [4,3-a] quinoxaline with a melting point of 212-215 ° C with a yield of 36%. Analytical result: Calculated for C 14 H 14 ClN 50: ° C 55.36%, © H 4.64% N 23 .06 Found:% C 54.91% H 4.59 ° N 22.76. Claims 1. A method for the preparation of new 4-amino [1,2,4] triazolo [4,3-a] quinoxaline derivatives of the general formula I, in which X and Xi independently of each other are hydrogen, chlorine or methoxy group, Ri represents a hydrogen atom, a lower alkyl group, a trifluoromethyl group or a phenyl group, R2 and Ra independently of each other represent a hydrogen atom, a lower alkyl group or an acyl group with 2 carbon atoms, provided that when R 1 represents a hydrogen atom or a methyl group, R a and R 1 always have the above meanings except for the hydrogen atom optionally in the form of their pharmaceutically acceptable acid addition salts, such that the corresponding 4-chloro derivative of general formula IIa or 2b, in which X, -Xi and Ri are as defined above, is reacted with an amine of formula HNR2R ", wherein R2 and R" are as defined above, with the proviso that R * and R "are as defined above with except for the acyl group, yielding "the corresponding 4-amino derivative, which possibly alternatively, if at least one of R * or R8 is hydrogen, it is reacted with acetic anhydride to give the desired 4-amino derivative with an acetyl moiety, and optionally the resulting compound of general formula I is converted to a pharmaceutically acceptable acid addition salt thereof. 2. The method according to claim The process of claim 1, wherein the reactions are carried out with a molar excess of the amine of formula HNR * R 'in an organic solvent which is inert under the reaction conditions. 3. The method according to p. A process as claimed in claim 2, characterized in that dimethylformamide is used as the reaction-inert organic solvent. 4. The method according to p. The process of claim 2, characterized in that the reactions are carried out at 0-60 ° C for 2 to 24 hours. 5. The method according to p. The process of claim 1, wherein the acylation of the 4-amino derivative is carried out under substantially anhydrous conditions using at least an equimolar amount of acetic anhydride. 6. The method according to p. The method of claim 5, wherein the molar ratio of the acid anhydride to the starting 4-amine compound is preferably 4: 1-25: 1. ^ * 7. The method according to claim A process as claimed in claim 1, characterized in that the acylation of the 4-amino derivative is carried out at a temperature of 20-140 ° C for 1/2 to 24 hours. 8. The method according to p. A process as claimed in claim 1, characterized in that the acylation of the 4-amino derivative is carried out in a neutral, anhydrous organic solvent which is inert under the reaction conditions. 9. The method according to p. The process as claimed in claim 8, characterized in that a halogenated hydrocarbon solvent is used as the neutral, anhydrous organic solvent which is inert under the reaction conditions. 10. The method according to p. The process of claim 1, wherein 1-ethyl-4-chloro- [1,2,4] triazolo [4,3-a] quinoxaline is reacted with ethylamine to give 1-ethyl-4-ethylamino [1,2 , 4] triazolo [4,3-a] quinoxaline. 11. A method for the preparation of new 4-amino [1,2,4] triazolo [4,3-a] quinoxaline derivatives of the general formula I, in which X and Xi independently represent a hydrogen, fluorine, chlorine, bromine or methoxy group , Ri represents a hydrogen atom, a lower alkyl group, a lower perfluoroalkyl group or a phenyl group; R2 and R8 independently of each other represent a hydrogen atom, a lower alkyl group, a phenylalkyl group containing 1-3 carbon atoms in the alkyl part or an acyl group with 2 to 5 carbon atoms, provided that at least one of R2 and R8 is as defined above, except for the hydrogen atom, when X and Xi are hydrogen and Ri is hydrogen or methyl, or Rt and R "together form a piperazine ring, except where X and Xi independently represent a hydrogen, chlorine or methoxy group, Ri is a hydrogen atom, a lower alkyl group, a trifluoromethyl group or a phenyl group, R9 and R9 15 independently of each other mean ato m hydrogen, lower alkyl or acyl group with 2 carbon atoms, provided that when Ri is hydrogen or methyl, R8 always has the meaning given above except for hydrogen optionally in the form of their pharmaceutically acceptable acid addition salts , characterized in that the corresponding 4-chloro derivative of general formula 2a or 2b, wherein X, X1 and R "and have the meaning given above, is reacted with an amine of formula HNRaR8, wherein R2 and R8 "Have the meaning given above, except for the acyl group, to give the corresponding 4-amino derivative which, if at least one of the substituents R" and R8 is hydrogen, is reacted with the anhydride of the corresponding alkanecarboxylic acid to give the desired 4-amino derivative with an acyl moiety, and optionally converting the resulting compound of general formula I into a pharmaceutically acceptable acid addition salt thereof. 12. The method according to p. The process of claim 11, wherein the reactions are carried out with a molar excess of the amine of formula HNR * R 'in an organic solvent which is inert under the reaction conditions. 13. The method according to claim A process as claimed in claim 12, characterized in that dimethylformamide is used as the reaction-inert organic solvent. 14. The method according to p. A process as claimed in claim 12, characterized in that the reactions are carried out at 0-60 ° C for 2-24 hours. 15. The method according to p. The process of claim 11, wherein the acylation of the 4-amino derivative is carried out under substantially anhydrous conditions using at least an equimolar amount of the anhydride of the corresponding alkanoic acid. 16. The method according to p. The process as claimed in claim 15, wherein the molar ratio of the acid anhydride to the starting 4-amine compound is preferably 4: 1-25: 1. The method according to claim 55 The method according to claim 11, characterized in that the acylation of the 4-amino derivative is carried out at a temperature of 20-140 ° C for 1 / 2-24 hours. A process as claimed in claim 11, characterized in that the acylation of the 4-amino derivative is carried out in a neutral anhydrous organic solvent which is inert under the reaction conditions. 19. The method according to claim A halogenated hydrocarbon solvent is used as the neutral, anhydrous organic solvent, inert under the reaction conditions. 141 382 X1 X NyN Formula XX 1 Formula 4 Formula Za ... JL PI with X ' = H; Formula la excluding ^ I ^ -NR2R3 ^ W "Scheme f Scheme 2 X 'IN xYYVa YAAfLocH3 fYztff i Xx'X * o ^ - RW £ tfr7 OCH, l Scheme Z cd Scheme 2 cont. Li x'" l "^ SN yizóre X1 i - "i" N ^ NyN Formula 2b xMAi, RN_N X l ^ T kJL, JL (XUH; X * H) X / ^ N ^ | R2R3 PL

Claims (19)

Claims 1. A method for the preparation of new 4-amino [1,2,4] triazolo [4,3-a] quinoxaline derivatives of the general formula I, in which X and Xi independently of each other represent a hydrogen atom, a chlorine atom or a methoxy group, Ri represents a hydrogen atom, a lower alkyl group, a trifluoromethyl group or a phenyl group, R2 and Ra independently of each other represent a hydrogen atom, a lower alkyl group or an acyl group with 2 carbon atoms, with the proviso that R 1 represents a hydrogen atom or a methyl group, and Ra and R "always have the above meanings except for hydrogen, optionally in the form of their pharmaceutically acceptable acid addition salts, such that the corresponding 4-chloro derivative of general formula 2a or 2b is in which X, -Xi and Ri are as defined above, are reacted with an amine of formula HNR2R ", where R2 and R" are as defined above, with the proviso that R * and R "are as defined above except the acyl group, yielding the "corresponding 4-amino derivative, which optionally Generally, if at least one of R * or R8 is hydrogen, it is reacted with acetic anhydride to give the desired 4-amino derivative with an acetyl moiety, and optionally the resulting compound of general formula 1 is converted to a pharmaceutically acceptable acid addition salt thereof. 2. The method according to claim The process of claim 1, wherein the reactions are carried out with a molar excess of the amine of formula HNR * R 'in an organic solvent which is inert under the reaction conditions. 3. The method according to p. A process as claimed in claim 2, characterized in that dimethylformamide is used as the reaction-inert organic solvent. 4. The method according to p. The process of claim 2, characterized in that the reactions are carried out at 0-60 ° C for 2 to 24 hours. 5. The method according to p. The process of claim 1, wherein the acylation of the 4-amino derivative is carried out under substantially anhydrous conditions using at least an equimolar amount of acetic anhydride. 6. The method according to p. The method of claim 5, wherein the molar ratio of the acid anhydride to the starting 4-amine compound is preferably 4: 1-25: 1. ^ * 7. The method according to p. A process as claimed in claim 1, characterized in that the acylation of the 4-amino derivative is carried out at a temperature of 20-140 ° C for 1/2 to 24 hours. 8. The method according to p. A process as claimed in claim 1, characterized in that the acylation of the 4-amino derivative is carried out in a neutral, anhydrous organic solvent which is inert under the reaction conditions. 9. The method according to p. The process as claimed in claim 8, characterized in that a halogenated hydrocarbon solvent is used as the neutral, anhydrous organic solvent which is inert under the reaction conditions. 10. The method according to p. The process of claim 1, wherein 1-ethyl-4-chloro- [1,2,4] triazolo [4,3-a] quinoxaline is reacted with ethylamine to give 1-ethyl-4-ethylamino [1,2 , 4] triazolo [4,3-a] quinoxaline. 11. A method for the preparation of new 4-amino [1,2,4] triazolo [4,3-a] quinoxaline derivatives of the general formula I, in which X and Xi independently represent a hydrogen, fluorine, chlorine, bromine or methoxy group , Ri represents a hydrogen atom, a lower alkyl group, a lower perfluoroalkyl group or a phenyl group; R2 and R8 independently of each other represent a hydrogen atom, a lower alkyl group, a phenylalkyl group containing 1-3 carbon atoms in the alkyl part or an acyl group with 2 to 5 carbon atoms, provided that at least one of R2 and R8 is as defined above, except for the hydrogen atom, when X and Xi are hydrogen and Ri is hydrogen or methyl, or Rt and R "together form a piperazine ring, except where X and Xi independently represent a hydrogen, chlorine or methoxy group, Ri is a hydrogen atom, a lower alkyl group, a trifluoromethyl group or a phenyl group, R9 and R9 15 independently of each other mean ato m hydrogen, lower alkyl or acyl group with 2 carbon atoms, provided that when Ri is hydrogen or methyl, R8 always has the meaning given above except for hydrogen optionally in the form of their pharmaceutically acceptable acid addition salts , characterized in that the corresponding 4-chloro derivative of general formula 2a or 2b, wherein X, X1 and R "and have the meaning given above, is reacted with an amine of formula HNRaR8, wherein R2 and R8 "Have the meaning given above, except for the acyl group, to give the corresponding 4-amino derivative which, if at least one of the substituents R" and R8 is hydrogen, is reacted with the anhydride of the corresponding alkanecarboxylic acid to give the desired 4-amino derivative with an acyl moiety, and optionally converting the resulting compound of general formula I into a pharmaceutically acceptable acid addition salt thereof. 12. The method according to p. The process of claim 11, wherein the reactions are carried out with a molar excess of the amine of formula HNR * R 'in an organic solvent which is inert under the reaction conditions. 40 13. The method according to p. A process as claimed in claim 12, characterized in that dimethylformamide is used as the reaction-inert organic solvent. 14. The method according to p. A process as claimed in claim 12, characterized in that the reactions are carried out at 0-60 ° C for 2-24 hours. 15. The method according to p. The process of claim 11, wherein the acylation of the 4-amino derivative is carried out under substantially anhydrous conditions using at least an equimolar amount of the anhydride of the corresponding alkanoic acid. 16. The method according to p. The process as claimed in claim 15, wherein the molar ratio of the acid anhydride to the starting 4-amine compound is preferably 4: 1-25: 1. 55 17. The method according to p. 11. A process as claimed in claim 11, characterized in that the acylation of the 4-amino derivative is carried out at a temperature of 20-140 ° C for 1/2 to 24 hours 18. The method according to p. A process as claimed in claim 11, characterized in that the acylation of the 4-amino derivative is carried out in a neutral anhydrous organic solvent which is inert under the reaction conditions. 19. The method according to claim A halogenated hydrocarbon solvent is used as the neutral, anhydrous organic solvent, inert under the reaction conditions. 141 382 X1 X NyN Formula XX 1 Formula 4 Formula Za ... JL PI with X ' = H; Formula la excluding ^ I ^ -NR2R3 ^ W "Scheme f Scheme 2 X 'IN xYYVa YAAfLocH3 fYztff i Xx'X * o ^ - RW £ tfr7 OCH, l Scheme Z cd Scheme 2 cont. Li x'" l "^ SN yizóre X1 i - "i" N ^ NyN Formula 2b xMAi, RN_N X l ^ T kJL, JL (XUH; X * H) X / ^ N ^ | R2R3 PL