RU2307124C1 - Bicyclic 1,4-piridotiazine-1,1-dioxides and method for production thereof - Google Patents

Abstract

FIELD: organic chemistry.

SUBSTANCE: invention relates to bicyclic 1,4-piridotiazine-1,1-dioxides of general formula I

wherein R₁ is chlorine or fluorine; R₂ is linear or branched alkyl, cycloalkyl, optionally reduced aryl or heteroaryl, etc. Method for production of said compounds includes reaction of acyclic sulfones with primary alcohols, preferably in presence of inorganic or organic such as carbonates or alkali metal hydroxides tertiary organic amines or base mixtures, preferably in aprotic bipolar media without solvents, or mixture thereof with water.

EFFECT: safe method for production of new compounds useful as drugs.

2 cl, 2 ex

Description

Technical field

The invention relates to the field of organic chemistry, namely to heterocyclic compounds that may find application as medical preparations.

State of the art

A known method of producing tricyclic derivatives of benzo-1,4-thiazine-1,6-dioxides based on 3,6-bis (vinylsulfonyl) -1,2,4,5-tetrafluorobenzene (Amosova S.V., Gostevskaya V.I. , Gavrilova G.M. et al., Chemistry of heterocytic compounds., 1996, No. 9, pp. 1955-1198) [1], (Amosova S.V., Gostevskaya V.I., Gavrilova G.M. and other Izv. AN Ser. Chem., 1996, No. 2, p.430-433) [2] using 3,6-bis (vinyl sulfide) -1,2,4,5-tetrafluorobenzene as an intermediate, obtained from hexafluorobenzene and sodium vinyl sulfide.

The method has obvious disadvantages, namely, in the synthesis of this basic substance, hazardous compounds are used that serve as constant sources of emergency situations in laboratories and in production: acetylene, hydrogen sulfide, divinyl sulfide, metallic sodium and liquid ammonia (Amosova S.V., Gostevskaya V . I., Gavrilova G.M. et al. J. Organ.chem., 1992, 28 (7), 1463-1466) [3], (Gavrilova G.M., Amosova S.V. Ros. Chem. G. (J. Ros. chemical chem. named after D.I. Mendeleev), 2005, vol. XLIX, No. 6. p. 69-76) [4].

A key step in this process is the preparation of sodium vinyl sulfide, which is synthesized from divinyl sulfide and sodium metal in liquid ammonia. The use of liquid ammonia as a solvent limits the temperature of the reactions to the boiling point of the solvent itself (-36 ° C). Divinyl sulfide is also toxic, it is not a commercial product, the method of its production is problematic, the stage of its production must also be included in the general scheme of the known process. Next, 3,6-bis (vinyl sulfide) -1,2,4,5-tetrafluorobenzene is oxidized to 3,6-bis (vinyl sulfone) -1,2,4,5-tetrafluorobenzene, which is involved in cyclization with primary amines. The method is limited to producing tricyclic compounds only spontaneously formed at elevated temperatures. The total yield of the five-stage method for producing cyclic products is low. These shortcomings significantly narrow the scope of the known method even in laboratory practice, we have not found patents based on this method.

Note that 1,4-pyridothiazine-1,1-dioxides were not obtained by this method [4], other traditional methods for the synthesis of cyclic sulfones also belong to benzene derivatives, but not to the pyridinium series (Lozinsky M.O., Demchenko AM , Shivanyuk AF “Selected methods for the synthesis and modification of heterocycles.” / Under the editorship of Kartsev VG M .: IBS PRESS, 2003, v.2, p.305-334) [5].

It is known that it is heterocyclic compounds, including pyridine derivatives, that act as the most promising objects for searching for drugs among them; the presence of fluorine atoms in the molecule also increases their potential pharmacological significance [4].

Object of the invention

The objective of the invention is to provide a method for producing new heterocyclic compounds of the pyridinium series, more technologically advanced, safe and cheap.

The problem is solved by creating a method for producing a new class of substances - bicyclic 1,4-pyridothiazine-1,1-dioxides of the general formula

where R ₁ is a fluorine or chlorine atom, R ₂ is branched or unbranched alkyl, cycloalkyl, reduced or not reduced aryl or heteroaryl, not necessarily substituted by oxygen and (or) nitrogen-containing fragments, one or more halogen atoms, which consists in the use of acyclic sulfones general formula (II)

where R ₁ is a fluorine or chlorine atom, R ₃ is a chlorine or bromine atom, in reaction with primary amines, preferably in the presence of inorganic or organic bases, preferably carbonates or hydroxides of alkali metals, tertiary organic amines or mixtures of bases, not necessarily in a solvent environment , better - in aprotic bipolar media, their mixtures with each other or with water.

Method description

The method involves the step of producing acyclic sulfones of the general formula (II), which proceeds in three successive stages (Scheme 1).

Scheme 1:

B is the foundation; (S) is a solvent; A is HBr, SOCl ₂ ;

(S ') is an organic acid or its anhydride; R ₃ is Cl, Br.

In the first stage, the corresponding sulfides (IV) are obtained, using commercial mercaptoethanol and polyhalogenated pyridines (pentafluoropyridine, 3-chloro-2,4,5,6-tetrafluoropyridine) in the presence of inorganic or organic bases, tertiary organic amines or mixtures of bases, not necessarily in a solvent environment, better in aprotic bipolar media, their mixtures with each other or with water.

Next, the residue of mercaptoethanol is converted into a reactive fragment - SCH ₂ CH ₂ R ₃ (R ₃ is chlorine or bromine atoms) by treating sulfides (IV) of HBr or SOCl ₂ in the presence of pyridine - according to known, simple and safe laboratory methods. In the last step, sulfides (V) containing the aforementioned reaction fragments are involved in the oxidation reaction in the presence of H ₂ O ₂ and an organic acid or its anhydride.

All stages of the process are carried out in safe conditions, with available commercial reagents, yields of intermediate (IV, V, II) products are at least 70%.

The final stages of the formation of 1,4-pyridothiazine-1,1-dioxides (I) occur at room temperature as a result of the interaction of acyclic sulfones (II) with equimolar amounts of primary amines in an organic solvent.

Examples of the method

Synthesis of acyclic sulfones of the general formula (II)

Synthesis of 4- (2-Bromoethylsulfonyl) -2,3,5,6-tetrafluoropyridine

Stage 1 (Scheme 1)

To a solution of pentafluoropyridine (5.4 g, 0.0319 mol) in 25 ml of CH ₃ CN, cooled to 0 ° C. mercaptoethanol (2.49 g, 0.0319 mol) was added. Next, triethylamine (3.23 g, 0.0319 mol) was added dropwise with stirring and cooling in an ice bath for 30 minutes. After the addition of triethylamine, the reaction mass was kept at room temperature for 1 hour. The end of the reaction was fixed by TLC (hexane: ethyl acetate, 2: 1) and ¹⁹ F. NMR. NaHCO ₃ (2.95 g, 0.0351 mol) was added to the reaction mass and evaporated under reduced pressure to an oily product. The resulting product was washed with CHCl ₃ , filtered through a paper filter, and the filtrate was evaporated. 7.184 g of an individual oily product was obtained (98% yield based on pentafluoropyridine). ¹ H-NMR (CDCl ₃ , δ, ppm): 2.38 (br s, 1H, OH); 2.75 (m, 2H, CH ₂ -O); 3.25 (m, 2H, CH ₂ -S). ¹⁹ F-NMR (CDCl ₃ , δ, ppm): 24.72 (m, 2F, F-3, F-5); 71.23 (m, 2F, F-2, F-6).

Stage 2 (Scheme 1)

HBr (14.64 g, 0.181 mol, 47% solution) was added to the product isolated in the first stage (4.11 g, 0.0181 mol). The resulting mixture was heated under reflux in a sand bath for 8 hours at 170 ° C. The end of the reaction was monitored by TLC (CHCl ₃ ) by the disappearance of the stain of the starting product. The reaction mass was diluted with 15 ml of H ₂ O and was extracted with CHCl ₃ (2 × 30 ml). The extract was dried with MgSO ₄ , filtered and evaporated. 4.54 g of an oily product was obtained (82% yield). ¹ H-NMR (CDCl ₃ , δ, ppm): 2.98 (m, 4H, S-CH ₂ -CH ₂ -Br). ¹⁹ F-NMR (CDCl ₃ , δ, ppm): 24.95 (m, 2F, F-3, F-5); 72.24 (m, 2F, F-2, F-6).

Stage 3 (Scheme 1)

The product isolated in the second stage (1.18 g, 0.004 mol) was dissolved in 5 ml of CF ₃ COOH. H ₂ O ₂ (2.76 g, 0.0284 mol, 35% solution) was added dropwise to the resulting solution and kept for 24 hours at room temperature. The reaction mass was cooled, the precipitate was filtered off, washed with Н ₂ О, dried first in air, then in a vacuum of a water-jet pump over NaOH. 1.18 g (yield 90%) of an individual product were obtained. The precipitate was crystallized from CHCl ₃ , 0.86 g of a crystalline product was obtained with mp = 138-139 ° C. Elemental analysis. Found: C 26.33, 26.48; H 1.39, 1.47; F 24.36, 23.63; Br 25.36, 25.61; N 4.7; S 9.88, 10.16. C ₇ H ₄ BrF ₄ NO ₂ S. Calculated: C 26.10; H 1.25; Br 24.81; F 23.60; N, 4.35; 0 9.94; S 9.96. ¹ H-NMR (CDCl ₃ , δ, ppm): 1.13 (m, 2H, CH ₂ -Br); 3.35 (m, 2H, CH ₂ -SO ₂ ). ¹⁹ F-NMR (CDCl ₃ , δ, ppm): 26.09 (m, F-3, F-5); 78.24 (m, 2F, F-2, F-6).

Synthesis of bicyclic 1,4-pyridothiazine-1,1-dioxides of the general formula (I)

Example 1. Synthesis of 5,7,8-Trifluoro-4- (3-methoxypropyl) -3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

To a solution of 4- (2-bromo-ethylsulfonyl) -2,3,5,6-tetrafluoropyridine (1 g, 0.0031 mol) in 10 ml of DMF was added 3-methoxypropylamine (0.2796 g, 0.0031 mol) and triethylamine (0.6598 g, 0.0065202 mole). The reaction mass was kept for 1.5 hours at room temperature and with stirring.

The progress of the reaction was monitored by TLC (hexane: ethyl acetate, 1: 1) and ¹⁹ F. NMR.

The reaction mass was poured with stirring in a cold saturated aqueous solution of Na ₂ CO ₃ . The precipitate was filtered off, washed with distilled H ₂ O, dried first in air, then in a vacuum of a water-jet pump over NaOH. Received 0.83 grams of an individual by TLC product, the yield is 86.8% based on 4- (2-bromo-ethylsulfonyl) -2,3,5,6-tetrafluoropyridine. The precipitate was crystallized from ethanol to obtain 0.53 g of a crystalline product.

Elemental analysis. Found: C 42.99, 42.74; H 4.33, 4.06; F 18.09, 18.41; N, 9.32; S 10.97, 10.56. C ₁₁ H ₁₃ F ₃ N ₂ O ₃ S. Calculated: C 42.58; H 4.22; F 18.37; N, 9.03; S 10.33. ¹ H-NMR (CDCl ₃ , δ, ppm): 1.83 (m, 2H, CH ₂ —CH ₂ —CH ₂ —O); 3.21 (s, 3H, CH ₃ -O); 3.31-3.53 (m, 6H, CH ₂ -N-CH ₂ , CH ₂ -O); 3.79 (m, 2H, CH ₂ —SO ₂ ). ¹⁹ F-NMR (CDCl ₃ , δ, ppm): 18.32 (m, 1F, F-8); 62.20 (m, 1F, F-7); 89.26 (m, 1F, F-5). Mp = 76 ° C.

Example 2. Synthesis of 8-Chloro-5,7-difluoro-4- (3-methoxypropyl) -3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

To a solution of 4- (2-Bromoethylsulfonyl) -3-chloro-2,5,6-trifluoropyridine (2.97 g, 0.00877 mol) in 25 ml of DMF was added 3-methoxypropylamine (0.78 g, 0.00877 mol) and triethylamine (1.86 g , 0.01842 mol). The reaction mass was kept for 18 hours at room temperature with stirring.

Monitoring the progress of the reaction was carried out using TLC (hexane: ethyl acetate, 3: 1) and NMR ¹⁹ F.

The reaction mass was poured with stirring in a cold saturated aqueous solution of Na ₂ CO ₃ . The precipitated oily precipitate was filtered off, washed with distilled H ₂ O, dried first in air, then in a vacuum of a water-jet pump over NaOH. Received 2.05 grams of an individual according to TLC product, the yield is 72% based on 4- (2-Bromoethylsulfonyl) -3-chloro-2,5,6-trifluoropyridine. The precipitate was crystallized twice from ethanol, 0.85 g of crystalline product was obtained, mp = 87-88 ° C.

Elemental analysis. Found: C 40.97, 40.63; H 4.11, 4.28; Cl 10.63, September 11; F 11.77, 11.58; N, 8.45; S 9.95, 10.23. C ₁₁ H ₁₃ ClF ₂ N ₂ O ₃ S. Calculated: C 40.43; H 4.01; Cl 10.85; F 11.63; N, 8.57; S 9.81.

¹ H-NMR (CDCl ₃ , δ, ppm): 1.91 (m, 2H, CH ₂ —CH ₂ —CH ₂ —O); 3.29 (s, 3H, CH ₃ -O): 3.35-3.52 (m, 6H, CH ₂ -N-CH ₂ , CH ₂ -O); 3.83 (m, 2H, CH ₂ —SO ₂ ).

¹⁹ F-NMR (CDCl ₃ , δ, ppm): 79.21 (d, 1F, F-7); 91.94 (d, 1F, F-5)

Below are the characteristics of the following bicyclic 1,4-pyridothiazine-1,1-dioxides obtained by similar methods, the product yields ranged from 70% to 90%.

4-Benzyl-5,7,8-trifluoro-3,4-dihydro-2H-pyrido [43-b] [1,4] thiazine-1,1-dioxide

Found: C 51.43, 51.77; H 3.59, 3.26; F 17.40, 17.52; N, 8.61; S 10.04, 10.13. C ₁₄ H ₁₁ F ₃ N ₂ O ₂ S. Calculated: C 51.22; H 3.38; F 17.36; N, 8.53; S, 9.77.

¹ H-NMR (CDCl ₃ , δ, ppm): 3.54 (m, 2H, CH ₂ -SO ₂ ); 3.75 (m, 2H, CH ₂ -N); 4.54 (s, 2H, N-CH ₂ -Ph); 7.34 (m, 5H, CH ₂ -Ph).

¹⁹ H-NMR (CDCl ₃ , δ, ppm): 16.65 (m, 1F, F-8); 62.78 (m, 1F, F-7): 90.04 (m, 1F, F-5). Mp = 91-92 ° C.

5,7,8-Trifluoro-4-pyridin-3-ylmethyl-3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 47.43, 47.76; H 3.43, 3.28; F 17.52, 17.47; N, 12.61; S 9.66, 9.54. C ₁₃ H ₁₀ F ₃ N ₃ O ₂ S. Calculated: C 47.42; H 3.06; F 17.31; N, 12.26; S 9.74.

¹ H-NMR (CDCl ₃ , DMSO-D ₆ δ, ppm): 3.74 (m, 4H, N-CH ₂ —CH ₂ —SO ₂ ); 4.57 (s, 2H, CH ₂ -Ru); 7.36 (m, 1H, H-5 '); 7.80 (d, 1H, H-4 '); 8.56 (d, 2H, H-3 ', H-4').

¹⁹ F-NMR (CDCl ₃ , DMSO-D ₆ δ, ppm): 16.49 (m, 1F, F-8); 61.94 (m, 1F, F-7); 89.17 (m, 1F, F-5). Mp = 151-152 ° C.

5,7,8-Trifluoro-4- (tetrahydrofuran-2-ylmethyl) -3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 45.12, 44.91; H 3.93, 4.18; F 17.49, 17.75; N, 8.70; S 10.11, 10.06. C ₁₂ H ₁₃ F ₃ N ₂ O ₃ S. Calculated: C 44.72; H 4.07; F 17.68; N, 8.69; S 9.95.

¹ H-NMR (CDCl ₃ , δ, ppm): 1.35-1.64 (m, 2H, H-3 '); 1.79-2.16 (m, 2H, H-4 '); 3.07-3.53 (m, 2H, CH-CH ₂ -N); 3.61-4.22 (m, 7H, N-CH ₂ —CH ₂ —SO ₂ , CH ₂ —O, CH — O).

¹⁹ F-NMR (CDCl ₃ , δ, ppm): 18.59 (m, 1F, F-8); 62.38 (m, 1F, F-7); 90.45 (m, 1F, F-5). Mp = 106-107 ° C.

5,7,8-Trifluoro-4-furan-2-ylmethyl-3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 45.37, 45.61; H 2.88, 2.99; F 17.72, 17.87; N, 8.73; S 9.92, 10.04. C ₁₂ H ₉ F ₃ N ₂ O ₃ S. Calculated: C 45.28; H 2.85; F 17.91; N, 8.80; S 10.07.

¹ H-NMR (CDCl ₃ , δ, ppm): 3.23 (m, 2H, CH ₂ -N); 3.94 (m, 2H, CH ₂ —SO ₂ ); 4.55 (s, 2H, N-CH ₂ -C); 6.30 (m, 2H, H-3 ', H-4'); 7.36 (s, 1H, H-5 ').

¹⁹ F-NMR (CDCl ₃ , δ, ppm): 18.58 (m, 1F, F-8); 64.86 (m, 1F, F-7); 91.73 (m, 1F, F-5). Mp = 76-78 ° C.

5,7,8-Trifluoro-4- (2-methoxyethyl) -3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 40.63, 40.88; H 3.82, 3.97; F 19.27, 19.45; N, 9.61; S 10.69, 10.84. C ₁₀ H ₁₁ F ₃ N ₂ O ₃ S. Calculated: C 40.54; H 3.74; F 19.24; N, 9.46; S 10.82.

¹ H-NMR (CDCl ₃ , δ, ppm): 3.31 (s, 3H, CH ₃ -O); 3.51 (m, 4H, CH ₂ -N-CH ₂ ); 3.62 (m, 2H, CH ₂ -O); 3.95 (m, 2H, CH ₂ —SO ₂ ).

¹⁹ F-NMR (CDCl ₃ , δ, ppm): 18.64 (m, 1F, F-8); 62.82 (m, 1F, F-7); 89.94 (m, 1F, F-5). Mp = 78 ° C.

4-Butyl-5,7,8-trifluoro-3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 44.97, 45.01; H 4.50, 4.73; F 19.24, 19.57; N, 9.40; S 11.23, 11.12. C ₁₁ H ₁₃ F ₃ N ₂ O ₂ S. Calculated: C 44.89; H 4.45; F 19.37; N, 9.52; S 10.90.

¹ H-NMR (CDCl ₃ , δ, ppm): 0.86 (t, 3H, H-4 ', J _4'z' 7.3); 1.27 (m, 2H, H-3 'J _3'4' 7.4); 1.54 (m, 2H, H-2 '); 3.25 (m, 2H, H-1 '); 3.27 (m, 2H, CH ₂ -N); 3.76 (m, 2H, CH ₂ —SO ₂ ).

¹⁹ F-NMR (CDCl ₃ , δ, ppm): 18.34 (m, 1F, F-8); 62.27 (m, 1F, F-7); 89.53 (m, 1F, F-5). Mp = 102-103 ° C.

4- (5,7,8-trifluoro-1,1-dioxo-2,3-dihydro-1H-1λ ⁶ -pyrido [4,3-b] [1,4] thiazin-4-ylmethyl) benzyl sulfamide

Found: C 41.44, 41.56; H 2.99, 3.03; F 13.75, 14.23; N, 10.36; S 15.92, 16.11. C ₁₄ H ₁₂ F ₃ N ₃ O ₄ S ₂ . Calculated: C 41.28; H 2.97; F 13.99; N, 10.31; S 15.74.

¹ H-NMR (DMSO-D ₆ , δ, ppm): 3.65 (s, 4H, N-CH ₂ —CH ₂ —SO ₂ ); 4.55 (s, 2H, N-CH ₂ -Ph); 7.13 (s, 2H, NH ₂ -SO ₂ ); 7.44 (d, 2H, H-3 ', 5'-Ph); 7.79 (d, 2H, H-2 - ′, 6'-Ph).

¹⁹ F-NMR (DMSO-D ₆ , δ, ppm): 16.81 (m, 1F, F-8); 62.09 (m, 1F, F-7); 89.03 (m, 1F, F-5). Mp = 201-202 ° C.

(5,7,8-Trifluoro-1,1-dioxo-2,3-dihydro-1H-1λ ⁶ -pyrido [4,3-b] [1,4] -thiazin-4-yl) -acetic acid, ethyl ether

Found: C 40.82, 41.36; H 3.73, 3.61; F 17.67, 17.73; N, 8.92; S 10.03. 10.14. C ₁₁ H ₁₁ F ₃ N ₂ O ₄ S. Calculated: C 40.74; H 3.42; F 17.58; N, 8.64; S 9.89.

¹ H-NMR (CDCl ₃ , δ, ppm): 1.25 (t, 3H, CH ₃ —CH ₂ —O); 3.59 (m, 2H, CH ₂ -N); 3.94 (m, 2H, CH ₂ -SO ₂ ): 4.14-4.37 (m, 4H, N-CH ₂ -COO, O-CH ₂ ).

¹⁹ F-NMR (CDCl ₃ , δ, ppm): 18.67 (m, 1F, F-8); 63.70 (m, 1F, F-7); 88.28 (m, 1F, F-5). Mp = 78-79 ° C.

8-Chloro-5,7-difluoro-4-pyridin-3-ylmethyl-3,4-dihydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 45.51, 45.26; H 3.07, 3.06; Cl 10.36, 10.53; F 11.29, 11.18; N, 12.20; S 9.31. 9.53. C ₁₃ H ₁₀ ClF ₂ N ₃ O ₂ S. Calculated: C 45.16; H 2.92; Cl 10.25; F 10.99; N 12.15; S 9.27.

¹ H-NMR (CDCl ₃ , DMSO-D ₆ , δ, ppm): 3.71 (m, 4H, N-CH ₂ —CH ₂ —SO ₂ ); 4.53 (m, 2H, N-CH ₂ -Py); 7.35 (m, 1H, H-5'-Py); 7.81 (m, 1H, H-6'-Py); 8.54 (m, 1H, H-2'-Py); 8.62 (s, 1H, H-4'-Py).

¹⁹ F-NMR (CDCl ₃ , DMSO-D ₆ , δ, ppm): 79.96 (d, 1F, F-7); 91.67 (d, 1F, F-5). Mp = 170-171 ° C.

8-Chloro-5,7-difluoro-4- (tetrahydrofuran-2-ylmethyl) -3,4-dehydro-2H-pyrido [4,3-b] [1,4] thiazine-1,1-dioxide

Found: C 41.87, 42.39; H 3.92, 3.89; Cl 10.63, 10.46; F 11.31, 11.43; N, 8.28; S 9.56, 9.69. C ₁₂ H ₁₃ ClF ₂ N ₂ O ₃ S. Calculated: C 42.55; H 3.87; Cl 10.47; F 11.22; N, 8.27; S 9.47.

¹ H-NMR (CDCl ₃ , δ, ppm): (CDCl ₃ , δ, ppm): 1.35-1.62 (m, 2H, H-3 '); 1.76-2.15 (m, 2H, H-4 '); 3.05-3.54 (m, 2H, CH-CH ₂ -N); 3.62-4.19 (m, 7H, N-CH ₂ —CH ₂ —SO ₂ , CH ₂ —O, CH — O).

¹⁹ F-NMR (CDCl ₃ , δ, ppm): (CDCl ₃ , δ, ppm): 79.37 (d, 1F, F-7); 93.01 (d, 1F, F-5). Mp = 115-116 ° C.

The above examples confirm the receipt of the claimed class of compounds - bicyclic 1,4-pyridothiazine-1,1-dioxides of General formula (I).

The proposed new compounds can find application as drugs for medicine and agriculture, as well as serve as intermediate products for the production of a large number of derivatives by replacing nucleophilic mobile fluorine atoms in them.

Information Sources Used

1. Amosova S.V., Gostevskaya V.I., Gavrilova G.M. et al. Chemistry heterocytes. Conn., 1996, No. 9, p. 195-1198.

2. Amosova S.V., Gostevskaya V.I., Gavrilova G.M. and others. Izv. AN Ser. Chem., 1996, No. 2, pp. 430-433.

3. Amosova S.V., Gostevskaya V.I., Gavrilova G.M. and others J. organ, chem., 1992, 28 (7), 1463-1466.

4. Gavrilova G.M., Amosova S.V. Grew up. Chem. g. (J. Ros. Chem. Society named after D.I. Mendeleev), 2005, vol. XLIX, No. 6, pp. 69-76.

5. Lozinsky M.O., Demchenko A.M., Shivanyuk A.F. "Selected methods for the synthesis and modification of heterocycles." Ed. Kartseva V.G. M .: IBS PRESS, 2003.v.2, p.305-334.

Claims (2)

1. Bicyclic 1,4-pyridothiazine-1,1-dioxides of the general formula (I)

where R ₁ is a fluorine or chlorine atom, R ₂ is a branched or unbranched alkyl, cycloalkyl, reduced or not reduced aryl or heteroaryl, not necessarily substituted by oxygen, and (or) nitrogen-containing fragments, one or more halogen atoms. 2. The method of obtaining bicyclic 1,4-pyridothiazine-1,1-dioxides, General formula (I)

where R ₁ is a fluorine or chlorine atom, R ₂ is branched or unbranched alkyl, cycloalkyl, reduced or non-reduced aryl or heteroaryl, optionally substituted by oxygen, and (or) nitrogen-containing fragments, one or more halogen atoms, which consists in the use of acyclic sulfones of the general formula (II)

where R ₁ is a fluorine or chlorine atom, R ₂ is a chlorine or bromine atom, which are synthesized from mercaptoethanol and polyhalogenated pyridines in the presence of inorganic or organic bases, tertiary organic amines or base mixtures, not necessarily in a solvent medium, preferably in aprotic bipolar media mixtures of them with each other or with water, then the mercaptoethanol residue is converted into a reactive fragment - SCH ₂ CH ₂ R ₃ (R ₃ - chlorine or bromine atoms) by treating the resulting HBr or SOCl ₂ sulfides in the presence of pyridine, then sulfides containing the above reaction fragments - SCH ₂ CH ₂ R ₃ (R ₃ are chlorine or bromine atoms), the final stages of the formation of 1,4-pyridothiazine-1 are involved in the oxidation reactions in the presence of H ₂ O ₂ and an organic acid or its anhydride, 1-dioxides (I) occur at room temperature as a result of the interaction of acyclic sulfones (II) with equimolar amounts of primary amines in an organic solvent.