SU586642A1 - Derivatives of imidazolidingo-(3,2-f)-pyrido-(2,3-b)- or imidazolidingo-(3,2-f)-pyrimido-(4,5-b)-(1,4)-thiazines and process for producing the same - Google Patents

Description

The invention relates to a method for producing a new heterocyclic system - imidazolidino (3.2-1) pyrido (2, 3-b) - or imidazolidino- (3,4) pyrimido (4,5-b) (1,4) thiazines.

Various heterocyclic systems are known, including condensed pyridine or pyrimidine and thiazine rings, which have a wide spectrum of biological effects. The closest 4 analogues of the target compounds are oxazolidino (3,2-) pyrido (2,3-b) and oxazolidino (3,2-4) pyrimido (4,5-13) (1, 4) thiazines containing pyrido or pyrimidothiazine system condensed with oxazole cycle 5, as well as pyrido (3,2-4,5) imidazolo (2,1-b (1,3) thiazines containing a pyri-imidazole system condensed with a 1,3-thiazine cycle, which also are biological 1 active compounds b

The invention is based on the synthesis of new heterocyclic systems in which pyrido- or pyrimidothiaanne systems are condensed with an imidazole ring, of the general formula

,

(I)

xXJ,

3 5.

where R is hydrogen, chlorine

R. - hydrogen, matoxy; R methyl, ethyl, propyl, butyl; X - N or CH,

possessing biological activity; A method for producing the proposed compounds is that the compounds of the general formula

about gf - with about

one /

Av

OCD

x

-S (

R.

To „and X have indicated

where R, t, meaning

reacted with ammonium acetate in organic acid when heated.

As organic acids, glacial acetic acid is used and the process is carried out at HE-SOO C.

The yield of the target products is 80-90%.

The structure of imidazolidino (3,2- |) pyrido (2,3-1) - and imidaeolidino (3, 2-.f) pyrimido (4, S-fe) (1,4) thiazines was confirmed by IR, IIMP- and mass spectrometry.

In the IR spectrum there are absorption bands of the group. NH in the region (3030 3290 cm-) and CO groups (1730-1780 cm). In the PMR spectra, the signal of the protons of the CH group is represented as two duolets with a constant of geminal interaction E 12 Hz,

In the mass spectrum of imidazolidino (3,2- {) pyrimido (4,) (1,4) -taaine, a peak of a molecular ion with a mass number of 280 is observed, as well as fragments caused by the release of a radical mass with a mass number of 29 from a molecular ion. Intense peak With a mass number of 29, refers to a fragment obtained by detaching the molecular ion CO and CONH-rpynn-71TJ: C 5 -kl J

Claims (6)

R $ 209 The identity of the compounds is verified chromatographically in a thin Layer on Silufol 254 in the system: ben: ol - ethyl acetate - alcohol (17: 3: 2). ZSromatograms are produced in UV light. Example 1. 1,2-dioxo-4 a-methyl-7-chlorimidazolidino (3,2-) pyrid (2,3-1e) (1,4) thiazine. A mixture of 1.0 g (3 mmol) of 1,2-dioxo-4 a-methyl-7-chlorooxazolidino (3,2- |) pyrido (2,3-b) (1,4) thiazine and 20 g (0 , 26 mol) ammonium acetate s 10 ml of glacial acetic acid is boiled for 5 hours, left overnight, 30-40 ml of water are added, the precipitate is filtered, washed with water / dried and obtain 0.94 g (96%) of the desired pr D) ukta in the form of colorless crystals, so pl. 298-300 С (from alcohol),. IR spectrum: 3240-3290 CM (NH) 1730 1780 cm- (CO amides), PMR spectrum in CyD N: if67 ppm, (3N-CH3); 3/44 ppm (quartet SCH), Rf 0.35 in UV light. Found,% i C 44.40; H 2.96; C1 13.53; N 15.32; S 11.73. C oHeClN O S. Computation; leno,%: C 44.52; H 2.96; C1 13.17; N 15.58, S 11.87. Note 2. 1,2-dioxo-4 a-et 7-chloroimidazolidio (3,2-f.) Pyrido (2,3-b) (1,4) tiaein. The compound was prepared as in Example 1 of 0.5 g (1.7 mmol) of 1,2-d oxo-4a-etl-7-chlorooxazo idino (3,2-f) pyrido (2.3-4e) (1.4) thiazine, yield 0.45 g (91%), in the form of colorless crystals, m.p., 263-264s (from spin 7e.) IR spectrum: 3080-3120 cm (NH); 1720-1760 cm- (CO amides), PMR spectrum in ..N: 0.78 ppm (tr plet sns out); 2.00 MD (quartet SNa C.HC); 3.54 ppm (kvar "et ssNg). RP 0.39. Found,%: From 46.30; H 3.58; C1 12.73; N 14.87; S 11.43. C 4H oClN30iS. Calculated,%: C 46.56; H3.52; C1 12.52; N 14.81; S 11.28. Primer, 1,2-dioxo-4a-prog Pil-7-chlorimidazolidine (3,2-f) pyrido (2,3-t) (1,4) thiazine. The compound was prepared analogously to example 1 of 1.0 g (3.3 mmol) 1,2 dioxo-4a-propyl-7-chloroxazolidino: (3,2- €) pyrido (2, 11,4) hyazine, yield 0.89 g (90%), in the form of colorless 1 crystals, so pl. 250-251s (from alcohol)., IR spectrum: 3080-3100 cm (NH); cm- (CO amides). HMR spectrum in CcDgN: 0.79 ppm; 1.30 ppm; 1.98 ppm, (7H-С ,, H); 3.52 M.D. (quartet SNL from SCH.). Rr 0.39; Found: C 48.37; H 4.05; N 14.42; S 10.76; Ci 11.82. ; C H ClNjOiS. : Calculated,%: C 48.40; H 4.04; C1 11.93 and 14.11, S 10.75, Example 4, 1,2-Dioxo-4a-bu gil-7-chlorimidazolidino (3,2-f) pyrido (2,3-) (1,4) thiazine,: The compound was prepared analogously to example 1 from 1.0 g (3.2 mol) 1,2 dioxo-4a-butyl-7-chloroxazolidino (3,2-) pyrido (2,3-b) ( 1,4) thiazine, yield 0.87 g (88%), in the form of colorless crystals, so pl. 262-264 C (from alcohol). IR spectrum: 3060-3120 cm (NH); 1740, 1760 cm (WITH amides). RJ 0.44 in UV light. Found,%: C 50.48; H 4.49; C1 11.68; N 13.67, S 10.22. С1ЫЗОз, 5.Calculated,%; C 50.08; H 4.49; C1 11.39; N 15.48, S 10.27. Example 5, 1,2-dioxo-4a-these 9-methoxyimidazolidino (3/2-) pyrimi (4,5-t)) (1,4) thiazine. 0.95 g (O, 12 mmol) 1,2-dioxo-4a ethyl 9-methoxy oxazolidino (3.2-4) pyrimido (4, 5-) (1, 4) thiazine, 1.8 g (2, 33 mol of) ammonium acetate in 15 ml of glacial acetic acid is heated for 2. h at. The next day, the reaction mass is poured into 50 ml of water and neutralized with ammonia, the precipitate is filtered off, washed with water, dried and obtain 0.27 g (79.4%) of the desired product as colorless crystals, mp. 240-241 ° C (from the alcohol). IR spectrum in CHCH: 3425 cm (NH 1765. Cm- (CO). PMR spectrum in CgDgN: 0.82 ppm (CH3 from GjHg); 1.41 ppm (CH from C- jHg) / 3.6 ppm (2H-SCH); 3.99 ppm (OST); 8.57 ppm (H-pyridine moiety) .R 0.5 (in the alcohol-benzene ethyl acetate system 2: 5: 5). Found: C 47.25; H 4.54 N 20.05, S 11.07. Calculated,%: C 47.13; H 4.32; N 1S.,. 98 S 11.44. Formula of the invention 1. Imidazolidino (3 4,2 HL) pyrido (2, 3-b) - or imidazo-idino {3,2-) pyrimido derivatives (4,5-b} (1,4) thiazines of the general formula v, where R is hydrogen, chlorine; R. is hydrogen, methoxy group; Hz is Methyl, ethyl, propyl, butyl, X is N or CI 2. The method for producing the compounds of claim 1, wherein compound total Formulas ф 8 where k, R, R, and X have the indicated meanings, react with ammonium acetate in an organic acid when heated. 3. The method according to claims 1 and 2, which is based on the use of acetic acid as an organic acid and the process is carried out at 80-100 ° C. Sources of information taken into account in the examination 1. German patent 1110651, 12 p 10, published. 1958. 2. Patent of England 990857, C 2 C, published. 1965. 3. The patent of Germany; 114 a55b, cl. 12 p 10/10, publ. 1963. 4. The patent of Japan 19070, cl. 16 E, published. 1966. 5. USSR author's certificate according to the application 2043251, c. 07 d 93/12, 1974 6. For the FRG 2429290, cl. C 07 D 513/16, published 1975.