SU1647003A1 - Thiazolopyrimidopyrimidine derivatives, process for preparing them, and 3-amino-5-methylthiazolo[3,2-a]pyrimidinium salts as starting materials - Google Patents

Abstract

This invention relates to heterocyclic compounds, in particular, to the preparation of thiazolopyrimidopyrimidines of phyla I (O where R is SbNdOCH3; RI means Svb: R - SbH5. RI means SbNb, CH3, COOC2H5, and salts of 3-amino-5-methylthiazolo 3,2-a pyrimidine f-ly II, fn. AN - «ft xH2N Rt (ll) where X is the residue of the acid CIO-) Br. CgHsSOa: Ri - CeHs with R - CbHlOss. and at R - CeHs RI - CeHs, CH3. СООС2Н5. which can be used as starting compounds for the preparation of thiazolopyrimidopyrimidines. The goal is to get new connections in a new way. Compounds of f-ly I are obtained by treating the salt of 3-amino-5-methylthiazolo (3,2-a} pyrimidine with a mixture of phosphorus oxychloride and dimethylformamide with heating and then with water. The starting compounds of f-II II are obtained by the reaction of 2-mercapto-6-methyl -4-substituted pyrimidines and a-substituted bromoacetonitriles or p-toluenesulfonateacetonitriles. 3 cf f-crystals, t. Fe

Description

The invention relates to new chemical compounds derived from the new heterocyclic system of thiazolopyrimidopyrimidines of the general formula

R

N

 {l)

where at R - СеН4ОСНз RI - CeHs.a at R - CeHs, Ri - CeHs. SNS, COOCaHs, to the new

the method of their preparation and to the new compounds of the thiazolo-3,2-a pyrimidine series of the formula R

AN, CH / Q xHgm R

00

where R and RI have the indicated meanings, and X is the acid residue (C104. Br. CeHsSOs) as starting materials for preparing the thiazolopyrimidopyrimidines of the formula (I).

The purpose of the inventions is the search for new compounds related to a new heterocyclic system containing a new combination of derthiazole and pyrimidine, a method for producing these compounds that can be used in the chemical-pharmaceutical and chemical-photographic industry, as well as the search for new compounds that can be used as source.

Example 1. 7- {p-Methoxyphenyl) -2-phenyl-b-formylthiazolo 3: 1,9,8-pyrimido 3,4-c pyrimidine.

Cool down to 0-5 ° C with 1 ml of phosphorus oxychloride and add 1 ml of dimethylformamide. 0.5 g (1 mmol) of 3-amino-5-metzl-7- (p-methoxyphenyl) -2-phenylthiazolo 3,2-a pyrimidini toluene sulfonate is added to the resulting mixture. The mixture is heated for 1 hour at an oil bath temperature (100-110 ° C). The resulting solution is poured onto 100 g of ice. The precipitate formed is filtered, dried in air, dissolved in chloroform and chromatographed on alumina. Chloroform is evaporated in vacuo, and the residue is triturated with alcohol. The output of 0.23 g, (60%), so pl.251 ° C.

Found,%: C 68.6; H 4.0: N 11.0; S 8.3.

C22H15N302S.

Calculated,%: C 68.57; H 3.90: N 10.91: S8.31.

Example 2. 7- {p-Methoxyphenyl) 2-phenyl-5-formylthiazolo 21, H1, 41: 1,9,8 -pyrimido 3, pyrimidine.

The procedure is carried out as in Example 1, using 0.45 g (1 mmol) of 3-amino-5-methyl-7- (p-methoxyphenyl) -2-phenyl-thiol 3,2-a pyrimidine perchlorate. Get the same as in example 1 product.

P. and m p 3. 2,7-Diphenyl-5-formyl-thiazolo 21, 3, 1,9.8-pyrimido 3; 4-c pyrimidine.

Cool down to 0-5 ° C with 1 ml of phosphorus oxychloride and add 1 ml of dimethylformamide. 0.48 g (1 mmol) of 3-amino-5-methyl-2,7-diphenylthiazolo 3,2-a pyrimidinium toluene sulfonate is added to the resulting solution. The mixture is heated at 100 ° C for 1 hour. The resulting solution is poured onto ice. The filter is filtered. Purify and isolate analogously to Example 1. Yield: 0.2 g (57%), m.p. 232 ° C.

Found,%: C 80.0; H 3.5: N 12.0; S 9.0,

C21 Hi3N3OS.

Calculated,%: C 80.00: H 3.66; N 11.83; 59.01.

Example 4. 2,7-Diphenyl-5-formyl-thiazolo 21, 3, 41: 1,9,8-pyrimido 3,4-c pyrimidine.

Carried out analogously to example 3, using 0.42 g of perchlorate 3-emino-5-methyl-2,7-diphenyithiazolo 3,2-a-pyrimidinium. Get the same as in example 3 product.

Example 5. 2,7-Diphenyl-5-formyptiazolo 21, 3.4: 1.9.8-pyrimido 3,4-c pyrimidine. Operations are carried out as in Example 3 at 80 ° C for 3 hours. The product is identical to that obtained in Example 3.

Example 6. 2-Metal-7-phenyl-5-forlimtiazolo 21, H1, 41: 1,9,8} -pyrimido 3,4-c pyrimidine.

1 ml of dimethylformamide and then 0.34 g (1 mmol) of 3-amino-2,5-dimethyl-7-phenylthiazolo 3,2-a pyrimidine bromide are added to chlorampheni phosphorus cooled to 0-6 ° C. . The mixture is heated at 80 ° C for 2 hours and poured onto ice. The precipitated product is filtered and purified analogously to example 1. Yield 0.23 g (43%), so pl. 262 ° C.

Found,%; C65.5; H4.0; N14.2; S 11.0.

CieHnNaOS.

Calculated,%: C 65.53; H 3.75: N 14.38; S 10.92.

Example 7. 7- (p-Methoxyphenyl} -5-formyl-2-toxycarbonyl thiazolo 21, H1, 41: 1,9,8 pyrimido 3.4-c pyrimidine.

Cool down to 0-5 ° C with 1 ml of phosphorus oxychloride and add 1 ml of dimethylformamide. To the mixture was added 0.4 g (1 mmol) of 3-pmino-5-methyl-7-phenyl-2-to -carbonyl-thiazolo 3,2-a pyrimidine bromide and heated at 70 ° C for 3 hours. The mixture was poured onto ice . The solution is extracted with chloroform, the chloroform extract is filtered through a layer of alumina, and the chloroform is evaporated in vacuo. Yield 0.25 g (71%). mp.219 ° C.

Found %: C 61.5: H 4.0; N 12.0: S 9.0.

CieHi3N303S

Calculated,%: C, 61.54; H 3.70; N 11.97; 59.12.

In the IR spectra of the obtained compounds, absorption bands are observed in the region of 1600–1680 cm 1, characteristic of stretching vibrations and C – 0 bonds.

In the PMR spectra (In CPZOOO, TMS is an internal standard), there are no signals from the C-CH3 group of the thiazolopyrimidium salts of formula (II), but signals from the protons of the substituents R and RI are observed (the proton of the formal group is 39.5-9.6 ppm .). besides, there are still signals of two aromatic protons of a closed heterocyclic nucleus. For example, for thiazolopyrimidopyridine 0) (R - CbH5, RI COOCnH3), signals of protons of the ethoxy group with chemical shifts of 1.51, t, 3N are observed. 4.59, sq. 2H, the signals of the protons of the phenyl group due to the influence of the electron pairs of the nearby

the nitrogen atom is represented by two groups: signals of ortho-protons 8.29, m, 2H; and so - protons - 7.68 ppm, m, 3N. The signal of the formyl proton is observed at 9.56 ppm, and the signals of aromatic protons at positions 4 and 6 are observed at 8–72 and 8.05 ppm. respectively.

Example 8, Salts of 3-amino-2-Pr7-P-5-methylchiazolo 3,2-e-pyrimidini (II).

A mixture of equimolar amounts (2-mercapto-b-methyl-4-p-methoxyphenylpyrimidine and a-bromo-a-phenylacetonitrile is heated at 100 ° C for 1 h. The melt is triturated with acetone, the product is filtered. To obtain perchlorates, process alcohol solution of sodium perchlorate.

Similarly, from 2-mercapto-6-methyl-4-substituted gshrimidines and "-substituted bromoacetonitriles or p-toluenesulfonate acetonitriles, soltiazoloZ, 2-a pyrimidine of formula (I) is obtained.

Characteristics of salts are given in the table. In the IR spectra of the compounds of formula (II) there are no stretching vibration bands N C in the initial nitriles, and there are N-H bonds in the range of 3000-3200 cm 1.

In the PMR spectra, signals of protons of amino groups, methyl groups in position 5, as well as signals of protons of substituents R and RL are observed. For example, for bromide 3-amino-2,5-dimethyl-7-phenylthiazolo 3,2-a pyrimidine signals are observed (in DMSO -De) with chemical shifts: 5.75 (2H. -MH2); 3.32 s. (3N, 5-CH3): 2.52 s. (3N, 2-CH3); 8.51 s. 1, 6-H); 8.38 m / 2H, 0-H): 7.70 m (ZN.Ag-H).

The shift of the ortho-protons of the phenyl group to the weak field is due to the influence of the electron pairs of the nearby nitrogen atom, which also confirms the structure of the reaction products.

Thus, the implementation of the proposed method allows to obtain derivatives of a new heterocyclic system, characterized by a new combination of derthiazole and pyrimidine, which can be used to create compounds with new properties.

Claims (3)

Claim 1, Thiazolopyrimidopyrim of the formula N Xx  Ri where at R - Ri Cehs, and prch R СеН5 Ri - СБН5, СНз, СООСаНб. 2. The method of producing thiazolopyrimidopyrimidines of the general formula () the fact that the salts of 3-amino-5-methylthiazolo 3,2-a pyrimidics formulas 20 oh cH3-ps R where X is the residue of the acid CI04, Br, CeHsSOs Ri - CbH-3 with R - CeH3Ch3, and with R - CeHs Ri - CbNb, CH3, COOCaHs, treated with a mixture of phosphorus oxychloride and dimethylformamide with heating, and then with water. 3. Salts of 3-amino-5-methylthiazolo 3,2-a pyrimidine of the General formula R AN h h SN / T4. hsh H2N R} where X is the acid residue, Br, CeHsSOa Ri - CeHs with R - CeH40CH3. and when R is CeHs, Ri is CeHs, CH3, COOC2H5. as starting compounds for the preparation of thiazolopyrimidopyrimidines of the general formula K -N 0 snooze m rt where at R - СеН40СНз RI - CeHs, and at R - CeHs Ri - CeHs, СНз. СООС2Н5.