SU1152518A3 - Method of obtaining isoxazole derivatives - Google Patents

Abstract

METHOD FOR PRODUCING MANUFACTURING OF ISOXAZOLES of the general formula B C1. / -CH-jO-NH-C-NHj, P w where B is C, -C-papil, characterized by the fact that the compound of the general formula R C 1 kHCN2-Cr, O CO where R has the indicated value, is reacted with cyanamide in water at room temperature followed by an increase to 100.

Description

3 Calculated,%: C 28.89; H 4.18; 23.24; From 14.70. Found,%: C 29.91; N. 4.68; N 23.40; All 14.62. The starting 3-methyl-4-chloro-5-aminooxymethylisoxazole can be prepared as described in Examples 2-4. Example 2. Preparation of 3-methyl-4-halogen-5-bromomethylisoxazole derivatives. 0.1 mol of the corresponding 3,5-di methyl-4-haloisoxazole is dissolved in 150 ml of anhydrous carbon tetrachloride. After the addition of 0.5 g of benzoyl peroxide, the solution is heated to boiling. 0.12 mol of N-bromosuccinimide is added to the mixture in half portions in small portions, after which the reaction mixture is boiled for the next 4-5 hours. After cooling, the resulting succinimide precipitate is filtered off. The remaining syrupy 3-methyl-4-halogen-5-bromomethylisox sol can be used further without further purification. Yield 90-100%. Example 3. Preparation of 3-methyl-4-halogen-5- (phthalimy doxymethyl) -isoxazole derivatives. 0.1 mol of 3-methyl-4-halogen-5-bro of methyl ocaeal is dissolved in 120 ml of anhydrous dimethylformamide. After the addition of 0.11 mol of M-hydroxyphthalamide and 0.11 mol of triethylamine, the mixture is heated for 2 hours in a water bath at. The reaction mixture is cooled, diluted with cold water, the precipitated crystalline precipitate is filtered off, washed with cold water and recrystallized. 2-Chlorine derivatives: yield 89%, so pl. 152-153 0 (ethanol). Calculated,%: C 53.54; H 3.10, N 9.57; C (12.11. Found: C 53.08; H 2.99 N 9.58; ce 12.15. 4-Bromo derivative: yield 90%, mp. 154-156 ° C (ethanol-water mixture) Calculated,%: C, 46.31; H, 2.59, N, 8.31; Br, 23.70; Found,%: C, 47.00; H, 2.59; N, 8.25; Br, 23.67. 4. Preparation of 3-methy 4-halogen-5-aminooxymethylisoxazole hydrochloride. 0.14 mol of 3-methyl-4-halogen-5 (phthalimidoooxymethyl) -isoxazole is dissolved in 500 ml of anhydrous methylene dichloromethane or dichloroethane. After adding 60 g 98. % hydrazine hydrate is stirred at room temperature for 16–20 hours. The phthaloyl hydrazide which is separated out is filtered off, washed with dichloroethane, and the filtrate combined with the washing liquids and evaporated to dryness. The residue is dissolved in 200 ml of anhydrous ether, the ether solution is dried over magnesium sulfate, concentrated to about a third and saturated with dry gaseous hydrogen chloride. The separated product is filtered off, washed with ether and recrystallized. Chlorine derivative: yield 87%, mp 198-200 0 (anhydrous ethanol). Calculated,%: C 30.17; H 4.05, N 14.08i C | 17.81; C8-17.81. Found,%: C 30.02; H 3.99; N 14.06; All 17.77; SG 17.78, 4-Bromo derivative: yield 83%, so pl. 180-182C (anhydrous ethanol). Calculated,%: C 24, 66; H 3.11, N11.50- C 14.56; Br 32.80. Found,%: C 25.11, H 3.08, N 11.37; C 14.50, Br 32.72. The compounds of formula 1 have a strong and relatively long-lasting blood pressure lowering effect. Thus, 3-methyl-4-chloroisoxazole-yl-methylenoxyguanidine causes a decrease in the blood pressure of mice and rabbits; The LDs for this compound are 340.0 mg / kg (intravenously, on the neck). In cats, the fortieth portion of the dose of LDgj (8.5 mg / kg willow weight) Z-methyl-4-chloroisoxazol-5-ylmethylenoxyguanidine, intravenously, reduces blood pressure by 40%. In anesthetized cats, the tenth part of the LD5-J dose, administered enteric, causes a strong and prolonged decrease in blood pressure: after 30 minutes after the introduction of blood pressure by 25%, and after 90 minutes after administration, it is 33% lower than prior to the administration of the test compound. However, the compound does not significantly affect the heart rate. Ten part of the dose of TJiyo L-oi-methyldopa (analogous to the action) with the introduction of enteric decreases blood pressure in rabbits 30 minutes later after administration - by 30%, and 90 minutes later

i11525186

after the introduction - by 37%, It means- (K-induced by the local introduction of the deck, that the strength of the effect of the derived country, i.e. the compound of formula

isoxazole and L -o-methyldof alone also have anti-inflammatory

for now. The advantage of compound action.

Formula 1 is that they are active- 5.

in oral and intravenous. Thus, the proposed

introduction, and L -o-methyldopa only allows obtaining new bioprioral, logically active derivatives of the

In addition, the tenth part of the dose of isoxazole, exhibiting the ability

LDjo 3-methyl-4-chloroisoxazol-5-ylmeti-lower blood pressure, i.e.

lenoxiguanidine, administered to rats, by activity previously unknown for

causes a 32% suppression of edema, this row of compounds.

Claims (1)

METHOD FOR PRODUCING ISOXAZOLE DERIVATIVES of the general formula where B is C, -C ₄ -alkyl, characterized in that the compound of the general formula R Ct CH _Z —O — NH _Z , where R is as indicated, is reacted with cyanamide in an aqueous medium at room temperature, followed by increasing it to 100. SU w, 1152518