SU550829A1 - Derivatives of dipyrimido [(4,5-)(5,4-)]-(1,4) thiazines and method of obtaining the same - Google Patents

Abstract

1 .. Derivatives of dipyrimido ^ (^, 5- b)

Description

subjected to cyclization when processing the base.

0829

3. The method according to claim 2, 3 a to it, in that hydroxides are used as bases. 5 alkali and alkaline earth metals

. The method according to claim 2, 3 a lucers and c in that dimethylformamide or lower alcohols are used as an organic solvent.

The invention relates to the field of synthesis of a previously unknown heterocyclic system, derivatives of dipyrimido (, 5-b) (5, -lO (1) thiazines, which can be used in the synthesis of biologically active compounds.

It is known that various derivatives of fentiazine find practical use as pharmaceuticals. It is also known that derivatives of fentiazine analogues possess valuable biological properties.

The aim of the invention is to develop a method for producing a new heterocyclic system — a tetraazo analogue of known biologically active derivatives of fentiazine, which can be used in the synthesis of biologically active compounds.

A new heterocyclic system is proposed - derivatives of dipyri midor1.5-b) (5, -1) (1,) thiazines of general formula I

where R and RJ may be the same or different and are OA1k or M (A1k) 2., where A1k is an alkyl group with 1-4 carbon atoms.

The method for preparing dipyrimido P, 5b) ((1, A) thiazines of formula 1 is that 5-amino-6-mercaptopyrimidine derivatives of Formula II are reacted with 5 nitro-6-chloropyrimidine derivatives of formula III in an organic a solvent in the presence of a base, the resulting dipyrimidyl sulfide of formula IV is acylated and the resulting acylation product of formula V is cyclized by treatment with base according to the following scheme

K / ushg. ,

 01V .. FWP.,.

R

.N and

R

,

he n s l R and R values are given above.

The structure of dipyrimido derivatives | (, 5-b) (5, t-l) (l) of thiazines is confirmed by the data of IR spectra.; In examples, the temperature is indicated in degrees Celsius.

Example 1., 9-Dimethoxy5H-dipyrimido (, 5-b) (5, -1) (b) thiazine ..

a) -Methoxy-5-amino-6-thio- (methoxy-5-nitropyrimidyl-6) -pyrimidine. To a solution of 1 g (6, t mmol) of methoxy-5-amino-6-mercaptopyrimidium in 30 ml of methanol containing 0, g of KOH, was added a solution of 1.2 g (6, k mmol) i-MetoKCM-5- HHTpo-6-chloropyrimidine in 20 ml of methanol.

The reaction mixture is left for a day at room temperature, the precipitated precipitate is filtered, washed with water and dried in air. Obtain 1.2 g (5%) of a yellow crystalline powder with so pl. 226-228 ° (alcohol). Additional quantity is obtained by evaporation of the filtrate. The total yield is 7883%.

Found: C 38.55; H 3.19. CioH oN604S

Calculated,% t With 38,70; H 3.2. IR spectrum: 3120, 3300 cm (NHg). .

b) 4-Methoxy-5 acetylamino-6thio- {A-methoxy-5-nitropyrimidyl-6) pyrimidine. A mixture of 1 g (3.2 mmol) + -methoxy-5-amino-6-thio- (4-methoxy-5-nitropyrimidyl-6) -pyrimidine and AZO ml of acetic anhydride is heated at 65-70. within 2 hours, acetic anhydride is distilled off, the residue is triturated with water, the precipitate is filtered off and dried in air. Get 1 g (91%) of a white crystalline powder with so pl. (alcohol). IR spectrum: 1730 cm ().

Found D: C 40.85: H 3.19.

,

Calculated D: C 40.90; H 3.43. .

c) |, 9-Dimethoxy-5H-dipyrimidr 3 | 1 (, 5-b) (5, -1) 3 (1,4) thiazine - (la)

To a solution of 3.5 g of PO mmol-methoxy-3-acetylamino-b-thio - (- methoxy5-nitropyrimidyl-b) -pyrimidine in 30 ml of dimethylformamide at 60-70 add 5 ml of i-KOH solution in methanol. The reaction mixture is stirred at 60-70 ° for 1 hour, cooled to 20 ° and the precipitated precipitate is filtered off. 1.83 g (71.2%) of a bright yellow crystalline powder are obtained with a mp. 2t6-2 8 (from dimethylformamide). IR spectrum: 3220 cm (NH) -. . ,

Found: C 45.49; H 3.46; N 26.68; S 12.23.

Calculated D: 45.62; H 3.44; N 26.60; S 12,18.

EXAMPLE 2 4-Methoxy-9-dime-and tylamino-5H-dipyrimido-G (A, 5-b) (5.1) (1,) tiazi n.

a) 4-Methoxy-3-amino-6-thio- (4-dimethylamino-3-nitropyrimidyl-6) -pyrimidium. To a solution of 1.6 g (10 mmol) -methoxy-3-amino-b-mercaptopyrimidine in 30 ml of methanol containing, 0.6 g CrH, was added a solution of 2.02 (10 mmol) -dimethylamino-3-nitro - 6 chloropyrimidine in 30 ml of methanol. The reaction mixture is left for a day at room temperature. The precipitate is filtered off, washed with water and dried in air. Get 3g (95) yellow crystals with

m.p. 185-187 (from ethanol). Spectrum: 3t50 cm, 3320 (NH).

Found: C 40.94; H 4.21.

Calculated,%: C 40.86; H 4.03.

b) -Methoxy-9-dimethylamino-5HlipyrimidoC (, 5-b) (3, -1) (1,) thiazine. A mixture of 3.6 g (11 mmol) -meo-to-5-amino-6-thio (-dimethylamino-5-nitropyrimidyl-6) -pyrimidine and 30 ml of acetic anhydride is heated at 65-70 ° for 2 hours, acetic anhydride is distilled The residue is triturated with water, filtered and dried in air. The resulting material was dissolved in 30 ml of dimethylformamide and at 60-70, 5 ml of an A% KOH solution in methanol was added. The reaction mixture is stirred at

0 60-70 ° for 1 hour, cooled to room temperature. The precipitate is filtered off. Obtain 1.7 g (63%) of a yellow crystalline substance, with so pl. 180 ° (from ethanol). IR spectrum: 3200 cm-CMN)

Found: C 47.9; H 4.35; N 30.61; S 11.85. ,,, Calculated,%: C, 8l; H 4.38;

0 N 30.42; S 11.6.

Example 3 -Limethylamino-9 methoxy-3H-dipyrimido and (, 5-b) (3, -1-) J (1, A) thiazine.

a) 4-Dimethylamio-5-amino-6-thio5 (-methoxy-3-nitropyrimidyl-6) -pyrimidine. To a solution of 1.7 g (10 mmol) + -dimethylamino-5-amino-6-mercaptopyrimidine in 30 ml of methanol containing 0.64 g of KOH, is added a solution

 1.9 g (Yu mmol) -methoxy-5-nitro6-chloropyrimidine in 30 ml of methanol. The reaction mixture is left for a day at room temperature. The solvent is distilled off to dryness, the residue is triturated with water, the precipitate is filtered off and dried in air. Obtain 3 g (92) of yellow crystals with so pl. 213-213 (from ethanol). IR spectrum: 3110, 3260 cm- (NHg).

0 Found,%: C 40.84; H 4.06.

C ,, To Newsp.

Calculated,%: C 40., 86; H 4.03.

b) -Dimethylamino-3-acetylamino-6-thio- (4-methoxy-5-nitropyrimidyl 5 6) -pyrimidine. A mixture of 3.2 g (10 mmol) of 4-dimethylamino-3-amino-6-thio - (- methoxy-5-nitropyrimidyl-6) -pyrimidine and 30 ml of acetic acid anhydride is heated at 65-70 ° for 2 hours, the solvent is distilled off to dryness, the residue is triturated with water and the filters are filtered off. Get H, g (95) of a white crystalline powder with so pl. (from aqueous methanol). IR spectrum: cm- ().

Found: C A2.42; H 4.03.

Calculated: C 42.73; H 4.14.

c) -Limethylamino-9-methoxy-5Nepiprimido C (5-b) (S.i-lOd) thiazine. To a solution of g (10 mmol) of Limethylamino-5-acetylamino-6-thio (4-methoxy-5-nitropyrimidyl-6) -pyrimidine in 30 ml of dimethylformamide at 160-70, 5 ml of JBopa KON in methanol was added. The reaction mixture is stirred at 60-70 ° for 1 hour, cooled to 20 °, the precipitate is filtered off. Obtain 1.75 g (B5%) of greenish, yellow crystals with so pl. 205-206 (from ethanol).

Found,%: C 47.96; H 4.50; N 30.56; S 11.15.

C "N60S. Calculated,%: C, 47.81; H 4.38; N 30.42; S 11.6.

Claims (4)

one·. Dipirimido derivatives £ (4,5 b) (5,4-1) 3 (1,4) thiazines of general form where K and K / may be the same or different and denote OA1k or Ν (Α1κ) ₂ , where A1k is an alkyl group with 1-4 carbon atoms. 2. The method of producing compounds according to claim 1, for the key you are concerned that the derivatives of 5-amino-6-mercap _(a topirimidine of formula II (pyrimidine of formula II where K / has the indicated meanings, is reacted with 5-nitro-b-chloropyrimidine derivatives of the formula III _ I ¹ 0 _ζ Ν An where has the specified values in the environment of an organic solvent in the presence of a base, formed dipyrimidyl sulfide of General formula IV 550829A1 where K and E, have the indicated meanings, are acylated and the resulting product of acylation of the general Formula V subjected to cyclization when processing the base. 550829 ⁴ 3. The method according to claim 2, since it is believed that hydroxides are used as bases. 5 alkaline L alkaline earth metals 4. The method according to claim 2, consisting in the fact that as the organic solvent using dimethylformamide or lower alcohol · 10 you. ]