SU247954A1 - METHOD OF OBTAINING? YAS- (PIRIMIDINYL) -ALCANES - Google Patents

Description

The invention relates to the removal of ibs and bms- (nirimidinyl) -alkyls, which are of interest as potentially physiologically active compounds.

The proposed method consists in the fact that 2-hydroxypyrimidine hydrochloride in the presence of 2 mol of sodium hydroxide or 2-hydroxypyrimidine sodium salt is reacted with dichloralkane, for example 1,4-dichlorobutap, in an organic solvent, for example dimethylformamide, at 50-150 ° C with the release of the pellet product in a known manner.

Example 1. Synthesis of 1,2-b “c- (2-oxopnrimidipil-: N) -etap I, RH, p 2. A solution of 9.05 g of NaOH is applied to a stirred suspension of g of 2-hydroxypyrimidine hydrochloride in 175 ml of isobutanol. in 10 ml of H20. The resulting mass is slowly heated to 80 ° C, 15 ml of 1,2-dichl, gorata | Na are poured in and boiled for 14 hours (t. C. 88-90 ° C). NaCl is filtered off and the solvent is distilled off from the filtrate under vacuum. The crystallized residue is dissolved in methanol-chloroform (: 10), filtered and partially evaporated. The precipitated product is filtered off (5 g, 40.6%). After recrystallization from a mixture of chloroform-, methanol (-1: 1.5), pure product I is obtained (R-H, n 2), t. Il. 268-270 ° C (decomposition).

c 55.27; 54.95; H 4.75; 4.76;

0 (.

Paideno,

/about. N 25.50, 25.86.

Calculated for CrNuHcOg,%: C 55.05; H 4.59; N 25.69.

Example 2. 1,4-bns- (2-oxo-4,6-dimethylnirimidinyl-: M) -butane I, R-CH3, 11 1- (2-oxo-4,6 - dimethylpyrimidinylN) -4- (4 , 6-dimethylpyrimidipoxy-2) - butaia P, R-CH3, p 4 and 1,4-bis- (4,6-dimethyl-pyrimidipoxy-2) -butane P1, R-CH3, 11 4.

To a stirred suspension of 22 g of dry sodium salt of 2-hydroxy-4,6-dimethyl irimidium in 220 ml of dry dimethylformamide at 75 ° C, 9.58 g of 1,4-dichlorobutya are poured, the mass is heated at 95-105 ° C for 9 hours and hot filter (first filtrate). The filter cake is triturated with dry acetone (2 × 40 ml) and filtered again (second filtrate). The residue is NaCl. The precipitate formed in the first filtrate is filtered off (third filtrate). The precipitate was triturated with dry acetone Vichale at room temperature (5 × 40 ml), then at reflux (7 × 40 ml) and filtered again (fourth filtrate). The acetone-insoluble product is dissolved in a mixture of aceto-chloroform (1: 1), filtered and after evaporation of the solvents, 0.15 g of crude product I (R-CH3, p 4) with a melting point is obtained. 230 ° C (decomposition). After evaporation of the acetone from the second and fourth filtrates, 5.3 g of crude product P1 {R-CH3, p. 4) Art. square 154-156,5 ° C. The solvent is distilled off from the third filtrate under vacuum. The residual solid is dissolved in 50 ml of chloroform and filtered. This product, after evaporation of chloroform, is triturated in 1 cup of acetone (10 × 50 ml) and filtered again (fifth filtrate). The undissolved residue is triturated in bottled water and 0.2 g of crude product III (R-C3S, p 4) is filtered off with m. Pl. 153-155 ° C. From an aqueous solution, 0.15 g of crude product I (R-CH3) is obtained with a mp. 210-220 ° C (decomposition). The solid product remaining after evaporation of acetone from the fifth filtrate is triturated in distilled water and 1.51 g of crude product III is filtered off (R-CH3, 11 4). From an aqueous solution, 9.85 g of crude product II (R-CH3, p 4) Art. square 121 -126 ° C. Total, crude products are obtained, g (%): 0.30 (1.32) I (R-CH3, R-4); 9.85 (43.30) II (R-CH3, p 4); 7.01 (30.81) III (R-CH3, p 4). The total yield of the three isomers is 17.16 g (75.43). Product I (R-CH3, p 4), after two-time recrystallization from hot ethyl cellosolve and drying in vacuum, melts with decomposition at 249-251 ° C (slow heating in the melting range). Found,%: C 63.39; 63.18; H 7.33; 7.50; N 18.55; 18.56. Calculated for Ci6H22N4O2,%: C 63.58; H 7.28; N 18,54. Product II (R-СНз, п -4) is recrystallized twice. Mz boiling water, its dry acetone, once from ethyl cellosolve, and twice more from boiling dry acetone, exist in vacuum and get a clean vent with a melting point of 137.8-138, 4 ° C (decomposition). Found,%; C 63.63; 63.56; H 6.93; 6.88; N 18.45, 18.63. Product III (R-CH3), after two-time recrystallization from boiling ethyl cellosolve and three times from boiling 40% ethanol and drying in vacuum, melts at 156-157.5 ° C (slow heating in the melting range). Found,%: C 63.48; 63.49; H 7.26; 7.49; N 18., 39; 18.32. IR and UV spectroscopy methods were used to prove the structure of the obtained compounds. Subject of the invention. A process for the preparation of bis- (pyrimidipyl) -alk5SB, characterized in that 2-hydroxypyrimidium hydrochloride in the presence of 2 mol of sodium hydroxide or 2-hydroxypyrimidine sodium salt is reacted with dichlorobutane, for example 1,4-dichlorobutane, in an organic solvent for example, dimethylformamide, reduced, at 50-150 ° C with the release of the target product in a known manner.