SU719507A3 - Method of preparing vincamenine or its salts or its quaternary salts or its molecular compounds - Google Patents

Description

(51) METHOD FOR PRODUCING VINCAMENINE,

OR HIS SALTS, OR HIS QUARTERLY SALTS,

OR HIS MOUNT, LECULAR CONNECTIONS

This invention relates to the preparation of a new synthetic analogue of vincamine alkaloid, namely vincamenine, of the general formula

The goal is achieved by the described method, namely that the compound form MVVlbl or its salt, or its quaternary salt, or its molecular compounds, possess valuable pharmacological properties. 15 The known method of decarboxylation of carboxylic acids 1 allows to obtain a new compound - Vincamenine I The purpose of the invention is the expansion of class 20 analogs of vincamine alkaloids with pharmacological properties. where in B is the aily-d / ™ group, the noos-it / HOOO CH2 is heated at a temperature of 80-300 ° C and the resulting vincamene is isolated in free form, "as salt, pl or quaternary salt, or molecular molecule compound by known methods. Example 1. 3.4 g (0.01 mol) of vipkam1IOBOH kis.1oty are heated in a flask, prediagnacio for dry fusion, in a nitrogen atmosphere in an oil or metal ball to the melting point (2 () 0 ° C) and the melt is kept in tepepe 1-2 hours at a temperature of 240-260 ° C. Having heated to the temperature of the floatable viik. The imipova gives up carbon dioxide at the same time, until the reaction is complete, keep still at a temperature of 240-260 ° C. from 100 parts of chloroform (14 parts of methanol). When the characteristic spot for vikopkamovoy acid disappears, the reaction may be considered complete. The residual melt is then dissolved in a water-immiscible solvent, such as efpre, benzene or dichloroethane, the organic solution is shaken twice, then after adding 10 ml of aqueous sodium hydroxide solution each time, shaken after the addition of 10 ml of distilled water. : 1 remove possible residues of a renrostinated intracellular acid. The aqueous phases are drained together and shaken with but one volume of the solvent, not mixed with water. The separated organic phase is combined with the previously separated organic solution, dried with anhydrous sodium sulfate, filtered, and the filtrate is evaporated in vacuo. In the residue, 2.70 g of injected oil (in quantitative yield) are obtained in the form of a light yellow oil. This oily product can only be unregulated at very high temperatures under vacuum; t. knp prn 10-4 Hg,. 208-210 C. 180 ° C (, in chloroform). The picrate of vipkamennaya is well crystallized, it is a compound; m.p. 170-172 ° C. The molecular compound formed with picrolonic acid is melted at NPP 218-220 ° C. Ci9H22N2. Calculated,%: C 82.37; H 7.83; N 10.07. Found,%: C 82.02; H 7.80; N 9.95. Example 2. Nostunayut, as in example 1 with the fact that the melt of the original substance can withstand 240-260 ° C for 3 hours. So nutem; Participate from 2.50 g of Vinka Renina (90% of theory) in the form of oil, the color of which is somewhat darker than that of the product, obtained in Example 1. Example 3. 3.24 g (0.01 mol) of anew capps are heated in flask designed for sulfonated, in a nitrogen atmosphere in an oil nlp metal bath until melting temperature and dilution are kept for 1-2 hours at a pH of 250-260 ° C. The resulting melt is then dissolved in a water-immiscible solvent, such as naphm, in ether, benzene or dichloroethane H, the organic solution is shaken twice each time with the addition of 10 ml and. sodium hydroxide solution and then one time with 10 ml of distilled water to remove possible residues of unreacted apovipcemic acid. The aqueous phases are then mixed together and shaken to the half a volume of an orgapic solvent that is displaced with water. The separated organic phase is combined with the previously obtained organic solution, dissolved with anhydrous sodium sulfate, filtered. The H filtrate is evaporated under vacuum. As a residue, 2.10 g of vinkamennna (76% of teorpp) are obtained as a light yellow oil. Pkrak of this product with t. Pl. 172 ° C. Example 4. Proceed as in example 3, with the difference that the rasklav initial product is incubated for 3 h at 250-260 ° C. So nutem noluchayut 2.00 g of cancer. Example 5. 2.78 g (0.01 mol) of the dissolved solution is dissolved in 9 ml of absolute ethanol and treated with 1 ml of a 36.5% solution of a salt of a salt solution. Hydrochloride B1I1camepine is precipitated by adding approximately nn times as much ether. The hydrochloride is first separated in the form of oil, and when standing in the refrigerator it is dismantled. In this way, 2.70 g of GNCl 3 hydrochloride are boiling; so nl 246-247 ° C. Lcc -50 ° C (, in chloroform). Ci9H22N2-HCl (mol. Weight 316.83). Calculated,%: C 72.02; H 7.94; N 9.83; CI 11.5. Found,%: C 72.15; H 7.98; N 9.10; C1 10.7. The procedure is 6. 6. 1.39 g (0.005 mol) is dissolved in 8 ml of ethanol and treated with a solution of 0.375 g of D-vinpoic acid in 2 ml of ethanol. The extracts are separated in oil from a solution. This oily product dissolves well in water. EXAMPLE 7 0.2 / 7 g (0.001 mol) of vincamenta is dissolved in 1.0 ml of acetone and treated at room temperature with 0.5 ml (1.15 g; 0.008 mol) of methyl iodond. After a short time, the oily canles are collected on the upper surface of the solid solution; When the product is not continuously mixed, the product starts to crystallize. The mixture was placed on the same day in the cooling unit, during which time the building was completed. The product was cleaned with water, washed with water, acetone, and dried.

In this way, 0.42 g of methyl iodide of vincamenin (71% of theory) is obtained with m. Pl. 275 ° C.

After recrystallization from ethanol, a 2 ° 155 ° C (in chloroform).

Ci9H22N2-CH3l (mol. Weight 420).

Calculated,%; C 57.38; H 5.80.

Found,%: C 57.20; H 5.73.

Claims (1)

1. The method of obtaining vinkamen formula / AT is a group Where BUT PC hnos SNG or its salts, or its quaternary salts, or its molecular compounds, characterized in that the compound of formula is heated at a temperature of 80-300 ° C and the resulting vincamene is isolated in free form, in the form of a salt or a quaternary salt or molecular compound. Sources of information taken into account in the examination 1. Weigand-Hilgetag. Experimental methods in organic chemistry. M., 1968, p. 814-818.