PL88804B1 - - Google Patents

Description

The present invention uses these substances mixed with known tableting aids such as starch, lactose, talc and the like. All known pharmaceutical tabletting and drageing agents can be used. The hydrochloride compounds mentioned in particular are used in the preparation of injection solutions because of their good solubility in water. Of course, it is also possible to inject water-insoluble compounds with the addition of known suspending agents, emulsifiers and / or dissolving aids. Example I. Preparation of the compound of formula 4. For a solution of 36.3 g (0.1) Moia) 3-hydroxypropyl) -4-methyl-7,8-dimethoxycumarine in 300 ml of anhydrous benzene is added, 1 g (0.1 mol) of triethylamine. Then, during about 30 minutes, while stirring, a solution of 25.66 (0.1 mol) of 3,4,5-triethpxycinnamic acid chloride in 100 ml of anhydrous benzene was added dropwise at room temperature and the mixture was stirred at this temperature for 2 hours, and then The mixture is heated and boiled for 5 hours, then the liberated triethylammonium chloride is filtered hot. The sludge is washed with water, 10% aqueous sodium hydrogen carbonate solution, again with water and dried with sodium sulfate. The solvent is evaporated off under reduced pressure and the residue is recrystallized from methanol. 52.6 g (85% of theory) of 3- [Y-morpholine- | 3- (3 ', 4 /, 5) -trimethoxycinnamonyloxy) propyl] - 4-methyl-7,8-dimethoxycoumarin are obtained. colorless crystals with a melting point of 168-175 ° C. The melting point of the hydrochloride is 183 ° C. Example 2 Preparation of the compound of formula 5. For a solution of 10.8 g (0.03 mole) of 3- (Y-piper) - dyno- β-hydroxypropyl) -4-methyl-7,8-dimethoxycoumarin and 3.3 g (0.033 mol) of triethylamine in 70 ml of dry dioxane, a solution of 8.6 g (0.033 mol) of acid chloride is added dropwise Trimethoxycinnamic acid in 30 ml of anhydrous dioxane. The reaction mixture is stirred for 2 hours at room temperature and for 5 hours at 60 ° C, the triethylammonium hydrochloride which has formed is filtered off while hot and the solvent is evaporated to dryness. with ethyl acetate, the acetate phase is washed with an aqueous sodium hydrogen carbonate solution, dried with potassium carbonate and the solvent is evaporated off under reduced pressure. If the residue is lysed from a small amount of ethyl acetate or benzene, 14 g (80.4% of theory) of 3- [γ-piperidine-fH3 ', 4', 5'-trimethoxycinnamoyl oxy) propyl] -4-methyl are obtained - 7,8-dimethoxycoumarins with a melting point of 160-162 ° C in a similar manner as in Examples I and II: 3- [Y-pyrrolidine-P- (3 /, 4 ', 5) -trimethoxycinnamoyl-oxy) -propyl ] -4-methyl-7,8-dimethoxycoumarin, m.p. 150-152 ° C. 3- [N-6-methyleneimine-p- (3 ', 4', 5'-trimethoxy-cinnamoyloxy) -propyl] -4-5-methyl-O-7,8-dimethoxy-coumarin, mp 123-125 ° C. ¦., ... «3- [Y-diethylamino-p- (3 /, 4 /, 5 / *. * Taymethoxycin-moyloxy) -propyl] -4-methyl-7,8-dimethoxycin, melting point bases 138-140 ° C. 3- [Y-thiomorpholine-p- (3 ', 4', 5'-trimethoxycinnamyloxy) propyl] -4-methyl-7,8-dimethoxycumarne, mp 165-167 ° C. PL

Claims (2)

Claims 1. A method for the preparation of new esters of base-substituted alkoxycinnamic acid heterocyclic compounds of the general formula I, in which R is a nitrogen-linked residue of an aliphatic, cycloaliphatic, araliphatic or aromatic amine with 2-10 carbon atoms or a residue of 5-, 6 - Or a 7-membered heterocyclic nitrogen base containing in the ring next to the nitrogen atom an appropriate number of methylene groups as well as optionally further oxygen, nitrogen or sulfur atoms, Rx and R2 represent alkoxy groups with 1 to 4 carbon atoms, R4 is the lower group alkyl with 1 to 3 carbon atoms and the symbols m and n represent the numbers 1, 2 or 3, characterized in that the compounds of general formula II, in which R, R, R 4 have the meaning given above, are acylated by with the aid of an alkoxycinnamic acid of the general formula (III), in which R2 and n have the meaning given above, if any of its active derivative in an inert organic solvent, or the acid binding agent is absorbed at a temperature between 10 ° C and the boiling point of the solvent used. 2. The method according to claim 3. The process of claim 1, wherein the acylating agent of formula III is 3,4,5-trimethoxycinnamic acid or a derivative thereof. 20 25 30 35 40 4588 804 R4 mm (R |) m, -CH2-CH-CH2-R Mutr 1 Ra S-CH2-CH-CHrR ÓH O Formula 2 H0X-CH = CH - (] y (R2) 2 / n \ Nz 6r 3 CH3 CH2-CH-CH2-N D H3C00CH3 CH II CH I H3CCr T 0CH3 OCH3 Formula 4 CH: H £ 0 OCH CHrCH-CHrl ^ O ÓO-CH = CH- ^ VXH3 sOCH, Formula 5 OZGraf. Order 437 (110 + 25 copies) Price PLN 10 PL