SU763338A1 - Method of preparing 2,4-dichloro-5-mono- or di-(2'-hydrooxyethyl)-aminopyrimidine derivatives - Google Patents

Description

The invention relates to a new process for the preparation of compounds not previously described, specifically derivatives of 2,4-dichloro-5-mono- or di- (2-hydroxy-5 ethyl) -aminopyrimidine, which can be used as intermediate products; s in the synthesis of biologically active compounds. It is known from the literature that 10 hydrolysis of 2,4-dihalide-5-di (2-haloalkyl) -aminopyrimidine derivatives under acidic catalysis conditions leads to the replacement of only halogen atoms with hydroxyl, in the pyrimidine ring l}. Methods of administering the p-oxieskyl minogroup to the 5 position of 2,4-dichloropyrimidines are not known to date. The aim of the invention is to develop a method for producing 2,4-dichloropyrimidine derivatives containing in the 5th position of the p -oxyethylamino group by selectively hydrolyzing the halogen atom 25 in the azotyprit chain in 2,4-dihalo-5-di (2-haloethyl) -5 -amino-b-3 1-positioned pyrimidines. The goal is achieved by the proposed method of obtaining. where the treatment of the medium P in the case of the aqueous 2,4-dichloro-5-mono- or 2-hydroxyethyl) -aminopyrimidine is obmusculus, CHjdHX .nHCnon hydrogen or methyl, chlorine, fluorine or. hydroxy group. The trick is that agalo-pyrimidine of the general formula AND dHe (xIy - JH2 (iHx (Ji R and R have the indicated meanings; X is a chlorine or fluorine atom, shakes equimolecular cicarbonate and silver nitrate in an aqueous-organic solvent effect, preferably wire 20–100 ° C for 0.5–24 h and, for example, acetone, alcohols, and dioxane mixed with water are used in solvent at a ratio that ensures the complete dissolution of the initial and final pyrimidine derivatives. replacing one or two chlo atoms In the aliphatic chain of compound I. The use of a mixture of nitrate and car- bonate is necessary to ensure the neutrality of the solution during the hydrolysis process, since nitric acid is neutralized with silver carbonate during the reaction. Depending on the ratio of the reactants and the reaction conditions it is possible to hydrolyze one or two halogen atoms in the aliphatic chain of a compound of formula P. The structure of all synthesized compounds is proved by elemental analysis data, chromatography in comparison with the corresponding these isomeric compounds (see examples) and confirmed by IR spectra (no carbonyl absorption band in the region of 1650-1800 cm), MPR-spectra (no signals of the H-pyrimidine cycle in the region of 10-11.5 ppm), as well as UV spectra (71 lchox 260-265 nm). Example 1. 2,4-Dichloro-5- (2-chloroethyl-2-hydroxyethyl) amino-6-methy-pyrimidine (I; R CH-5; R N). A mixture of 18 g (0.06 mol) of 2,4-dichloro-Z-di- (2-chlorostil) -amino-b-methylpyrimidine, 10.2 g (O, 06 mol) of nitric acid silver, 16.6 g ( 0.06 mol of silver carbonate in 240 ml of 50% acetone is heated at 70-75 ° C and with stirring for 4.5 hours. Salts are filtered (here and in all subsequent examples, silver salts are quantitatively regenerated as insoluble in the water of chloride gray ribs). The mixture is washed with acetone, the combined filtrate is evaporated in a vacuum up to 50 ml, the precipitated oil is extracted with chloroform (3x100 ml) and dried over anhydrous alumina. The chloroform solution is treated with clarifying charcoal, passed through a layer of alumina (5 cm), chloroform is completely evaporated in a vacuum, the residue is re-precipitated from the minimum amount of hot benzene with a fivefold excess of dry hexane and kept in a refrigerator overnight. Obtain 13.9 g (81.5%) (1; R N) in the form of light yellow crystals with so pl. 53-54; Rr 0.24 in the system chloroform-hexane (2: 1) per Abdr 1U degree of activity. Found,%: C 38.04; H 4.17; N 14.81; All 37.53. C () Calculated,%: C 37.98; H 4.25; -N14.77; -CI 37.58. EXAMPLE 2 2,4-Dichloro-5- (2-chloroethyl-2 -oxyethyl) -aminopyridine. (1; R x C). A mixture of 5.9 g (0.02 mol) 2,4-dichloro-5-di- (2-chloroethyl) -aminopyrimidine 3.4 g (0.02 mol) of silver nitrate, 5.53 g of fO, 02 mol) silver carbonate in 100 ml of 70% ethanol is heated at and with stirring for 8 hours. The salts are filtered, washed with alcohol, the combined filtrate is evaporated to 20 ml on a rotary vacuum evaporator at a temperature not exceeding 50 ° C. The residues are cooled, extracted with methylene chloride (3x50 ml) and the extract is dried over anhydrous alumina. The matshalt is decolorized with BAU coal, evaporated under vacuum and the residue is recrystallized twice from benzene hexane (1: 4). Obtain 4.6 g (79%) (T; R) In the form of light yellow crystals with so pl. 60-62 C; , 24 in the system chloroform-gaksan (2: 1) on AE 0 1U degree of activity. Found 1: c 35.19; H 3.81; C1 39.07; N 15, “7. Calculated,%: C 35.51; H 3.73; C1 39.31; N 15.53. Froze 2,4-Dichloro-5- (2-fluoroethyl-2-hydroxyethyl) -amino-6-methylpyrimidine () is prepared from 2,4-dichlorop-5- (2-fluoroethyl, 2-chloroethyl) amino-6- methylpyrimidine, as described in example 1, at 70 ° for 6 h in an environment of 60% vrdn dioxane-. Yield 85%; light yellow oil 0,22. Found,%: C 40.45; H tt, k7; N 15.49; 01 26.61; F 6.89. N ,, 0 Calculated: С 40.31; H 4.51; N 15.67; C1 26.45; , F 7,09P rmmep 4. 2,4-Dichloro-5-di- (2 -oxyethyl) amino-6-methylpyrimidine (, R CH.x;). A mixture of 9 g (0.03 mol) 2,4-dichlorop-5-di- (2-chloroethyl) amino-6-methylpyrimidine, 10.2 g (0.06 mol) of silver nitrate and 16.56 g (0.06 mol) of silver carbonate, in 250 ml 60% ethyl alcohol is boiled under stirring for 6 hours. The salts are filtered, washed with alcohol. The combined aqueous-alcoholic solution is evaporated completely in vacuo, the slightly toyled residue is dissolved in 150 ml of chloroform and dried over CaCtj. The solution is passed through a layer of alumina, the solvent is distilled off in vacuum, and the residue is recrystallized twice from benzene-hexane (1: 3). With prolonged standing in the refrigerator, product crystallization occurs. 7.9 g (80%) (H) are obtained in the form of light yellows.

soft crystals with so pl. 24-2TS; , 18 in the system chloroform-hexane (2: 1) at 1U degree of activity.

Found,%: C 40.71: H 5.03; N 15.67; CE 26.74.

C, jH CezNjO

Calculated,%: C 40.61; H 4.92; N 15.79; Cr 26.65,

PRI me R 5. 2,4-di- (2-oxypropyl) amino-6-methylpyrimidine ().

Prepared from the compound of the formula I () under the conditions described in example 4, at room temperature for 24 hours. A WALKHOD 73%; light yellow oil; , 16 in the system chloroform-hexane (2: 1) at AE203 of the level of activity.

Found,%: C 44.88; H 5.77; N 14.21; Ct 24.23.

C n ,,.

Calculated,%: C 44.91; H 5.82; N 14.28; Ct 24.11.

Claims (3)

1. A method for preparing 2,4-dichloro-5-mono- or di- (2-hydroxyethyl) -aminopyrimidine derivatives of the general formula ej CjHzdhx  1HgSnon (Jl where R and R are hydrogen or X - chlorine atom, group, distinguished. with rahaloidpyrimidine total where R and R have the indicated meanings; X is a chlorine or fluorine atom, is treated with an equimolecular mixture of silver nitrate and carbonate in an environment of aqueous-organic solvents with 2. Method POP.1, characterized in that the process is carried out at 20-100 ° C for 0.5-24 hours. Sources of information taken into account in the examination 1. USSR author's certificate number 116912, cl. A 61 K 31/505, 1954. 2. Authors certificate of the USSR 453406, cl. C 07 D 239/42, 1972. 3. USSR author's certificate number 130044, cl. C 07 O 239/10, 1952.