SU650506A3 - Method of obtaining 2-thienyl-(4,5-dimethyl-2-pyridyl) ketone or salts thereof - Google Patents

Description

(54) METHOD OF OBTAINING

2-TIENYL- (4,5-DIMETHYL-2-PYRIDYL) -CETONE OR ITS SALTS

one

The invention relates to a process for the preparation of 2-thienyl (4,5-dimethyl-2-pyridyl) ketone or its salts, which can be used in medicine.

The alkylation of pyridine N-oxide with dimethyl sulfate 1 is known, as well as the replacement of 1-alkoxypyridinium salts with sodium cyanide to form 2-cyano derivatives 2. In addition, it is known to produce ketones from nitriles and organometallic compounds 3.

The purpose of the present invention is to develop a method for producing a new chemical compound, based on known reactions, and an intermediate and product for the pharmacologically active compound, as well as having a pharmacological activity.

The goal is achieved by the method of obtaining 2-thienyl- (4,5-dimethyl-2 - pyridyl) -ketone of formula I

or its solei.

The method is that the 3,4-dimethylpyridine N-oxide is reacted with dimethyl sulfate and then with sodium cyanide under a nitrogen atmosphere. The resulting 2-cyano-4,5-dimethylpyridine of the formula P

, -№

use

U

SNS

SNS

subjected to interaction with 2-thienyllithium in a nitrogen atmosphere. The desired product is isolated or salified, for example, hydrochloride. Example 1. Preparation of 2-cyano-4,5-dimethylpyridine.

To 123 g (1 mol) of thoroughly dried and crushed L-hydroxy-3,4-dimethylpyridine, under a nitrogen atmosphere, with vigorous stirring, 126 g are added dropwise

Claims (3)

(1 mol) of dimethyl sulfate, free from sulfuric acid impurity, maintaining the temperature of the reaction mixture in the range of 80-90 ° C. At the end of the tide, the mixture is heated for 2 hours at 100 ° C. In another apparatus, 170 g (3.5 mol) of sodium cyanide are dissolved in 570 ml of water with vigorous stirring for 1 h under a nitrogen atmosphere. The previously obtained N-methoxy-3,4-dimethyl-pyridine motilsulfate is dissolved in 250 ml of water and added to cyanic soda solution, with external cooling of the apparatus, maintaining the temperature in the range from 0 to -5 ° C. Then the reaction mixture is stirred for 24 hours at room temperature under a nitrogen atmosphere. The reaction mixture is then extracted with chloroform, the chloroform layer is dried over anhydrous magic sulphate, the dried extract is filtered, and the chloroform is distilled off. 69 g of a dark viscous liquid are obtained, which is chromatographed on a column of silica gel using benzene as an eluant, and 57.5 g of a mixture of cyanopyridines is obtained, from which 22.5 g of 2-cyano-4 is obtained by cooling to 5 ° C , 5-dimethylpyridine. Upon recrystallization from acetone, m.p. 77-78 ° C. Calculated,%: C, 72.70; H 6.10; N 21.30. CsHsNs Found;%: C 72.61; H 6.17; N 20.93. Example 2. Getting 2-thienyl- (4,5-dimethyl-2-pyridyl) -ketone. A solution of 26.8 g of thiophene in 70 ml of anhydrous ether is introduced into a flask, which is cooled (external cooling) to temperature from -5 ° C to -10 ° C. Into the resulting solution is dripped in drops over 2 hours, under a nitrogen atmosphere, 375 ml of 0.85 volts. ethereal solution of freshly prepared butyl lithium. The reaction mixture is then allowed to warm to room temperature, after which it is boiled at reflux temperature for 0.5 h. Then the reaction mixture is cooled to a temperature of from -10 to -20 ° C and a solution of 28.2 g of 2- is added dropwise. cyano-4,5-dimethylpyridine in anhydrous benzene. Prilification lasts 30 minutes, continue for another 0.5 h to heat at reflux temperature. After cooling, 250 ml of 30% aqueous hydrochloric acid are poured in and everything that boils below 100 ° C is removed by distillation. The resulting aqueous solution is heated at reflux temperature for 1 hour, alkalinized with 50% aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic layer is dried with anhydrous sodium sulfate, the solvent is distilled off under vacuum. Obtain 45.5 g of the crude solid product, which is recrystallized from acetone and receive 39.2 g of pure product. Yield 85%. Upon further recrystallization from acetone, m.p. 101 -103 ° C. Calculated,%: C, 66.35; H 5.10; N 6.45; S 14.75. CisHiiNSO Found:%: 66.31; H 5.11; N 6.24; S 14.31. Claims 2-thienyl (4,5-dimethyl-2-pyridyl) ketone of the formula or its salts, characterized in that the 3,4-dimethylpyridine N-oxide is reacted with dimethyl sulfate and then with sodium cyanide in the atmosphere nitrogen, the resulting 2-cyano-4,5-dimethylpyridine of the formula is subjected to interaction with 2-thienyl in nitrogen atmosphere. Sources of information taken into account in the examination 1.Pakett L. Fundamentals of modern chemistry of heterocyclic compounds. M., 1971, p. 200 2. In the same place 212. 3. Buhler K., Pearson D. Organic syntheses. M., 1973, p. 193.