DE1067033B - Process for the preparation of basic substituted monoethers of 2-methyl 5 8-dioxy-4'5 6,7-furano chromons - Google Patents

Description

GERMAN

In German Patent 924 693, basic substituted monoethers of 2-methyl-5,8-dioxy-4 ', 5': 6,7-furanochromone are used described the therapeutic effect very similar to the effect of khellin show are less toxic than the KheUin and - im In contrast to khellin, which is difficult to dissolve in water - at least in the form of its salts or quaternary Ammonium compounds are easily soluble in water and are therefore well suited for injection purposes. '

These known therapeutically effective basic ethers are produced by converting the 2-methyl-5,8-dioxy-4 ', 5': 6,7-furanochromons with a halide of a lower tertiary alkylamine, optionally in the form of its hydrohalide.

It has been found that, surprisingly, it is very easy to obtain similar basic monoethers with pronounced khellin-like action if 2-methyl-S, 8-dioxy-4 ', 5': 6,7-furanochromone - hereinafter referred to as khellinquinol - is used Basically substituted _: propylene oxides of the general formula

for the production of basic substituted

Monoether of 2-methyl-5,8-dioxy-

4 ', 5': 6,7-furanochromons

Applicant:

Chem. Pharmaz. factory

Dr. Hermann Thiemann G.m.b.H.,

Lünen (Westphalia), Kirchstr. 12th

Dr. Helmuth Schäfer, Hamburg-Fuhlsbüttel,
has been named as the inventor.

reacted, in which R ₁ and R _{2 represent} lower alkyl radicals with 1 to 4 carbon atoms or together with the nitrogen atom a saturated heterocyclic ring, in particular a piperidine or morpholine ring.

The basic epoxy accumulates without the use of ..... further aids and the epoxy ring bursts onto the 8-position ÖH group of the ¹ khellinquinol.

The reaction, which takes place in a suitable organic solvent and conveniently in an inert gas atmosphere is carried out according to the following equation:

CH ₃ +; N -CH ₂ -CH-CH ₂

OH O

CH ₂ -CH-CH ₂ -N;
OH

The basic khellinquinol ethers obtained in this way can be used in a manner known per se Acids are converted to salts or with alkyl halides to form quaternary ammonium compounds.

The secondary OH group in the side chain of the compounds prepared according to the invention offers one good starting point for further syntheses or substitutions. For example, it can be etherified or esterified will.

The compounds produced by the process described act in the same way as khellin spasmolytic and expanding on the coronary vessels; however, they are much less toxic than khellin and, in the form of their salts, are very soluble in water. Your salts

.909 638/377

15th

can also be used as solubilizers for KheUin.

example 1

Kheliinquinol-8- (7-diethylamino- | S-oxy) propyl ether

23.2 g of KheUinchinol are heated to boiling in 150 ecm of ethanol while stirring and passing nitrogen through. 15.5 g of 1-diethylaminopropane epoxide (2,3) are added dropwise over the course of 1 hour. The reaction mixture is then refluxed for a further 3 hours, the KheUinchinol slowly going into solution. With about 12 ecm conc. Hydrochloric acid is weakly acidified and evaporated to dryness in vacuo. The residue is taken up with 150 ecm of water, the insolubles are filtered off and the crude base is removed from the filtrate by adding 10% sodium carbonate solution. This is taken up in benzene, the benzene is distilled off in vacuo and the dark residue is recrystallized from cyclohexane. One erhält.so in good yield the KheUinchinol-8- (ydiäthylamino- / S-oxy) -pröpyläther in the form of yellow crystals, melting at 99 ⁰ C. ^ao;

This base is obtained by dissolving it in 5 times the amount of absolute alcohol and then using it gaseous hydrochloric acid neutralized, the hydrochloride in the form of yellowish crystals from 198 to 199 ° C.

One part by weight of the hydrochloride dissolves in 1.5 parts by weight of water at 20 ° C. and gives a 40% solution. .

Example 2
KheUinchinol-8- (γ-piperidino - ^ - oxy) -propylether

You work as in the example !, but replaces the 1-diethylamino-propane epoxide (2,3) by 16.9 g of 1-piperidino-propane-epoxide (2,3). From the resulting as in Example 1 The crude product is obtained by recrystallization from cyclohexane, the khellinquinol-8- (γ-piperidino-jS-oxy) propyl ether in the form of yellow crystals with a temperature of 124 ° C.

Dissolved in ethanol, fouls after neutralization with ethanol Hydrochloric acid, the hydrochloride of this base with a temperature of 223 to 224 ° C.

This hydrochloride dissolves to one part by weight in Gewichtsteüen water at 20 ° C, giving a 23 ° / ₀ resulting solution.

'Example 3'

Khellinquinol 8- (y-dibutylamino / S-oxy) propyl ether

As indicated in Example 1, 11.6 g of khequinol are added to 80 ecm of methanol with 10.5 g of 1-dibutylamino-2,3-epoxypropane in 10 ecm of methanol. The basic ether is obtained by recrystallization from cyclohexane in the form of yellow crystals with a temperature of 89 to 90 ° C. To represent the hydrochloride, the base is dissolved in ethanol dissolved and neutralized with gaseous hydrochloric acid. The hydrochloride crystallizes in pale yellow crystals from F. 202 to 203 ° C.

One part of this hydrochloride dissolves in 6 parts Water at 20 ° C, which results in a 10% solution.

Claims (1)

Claim: Process for the preparation of basic substituted monoethers of 2-methyl-5,8-dioxy-4 ', 5': 6,7-furanochromone (KheUinchinols), characterized in that KheUinchinol in an organic solvent with basic substituted propylene oxides of the general formula ^ N-CH ₂ -CH-CH ₂ ■ ■■ 0 ■ in which R ₁ and R _{2 represent} lower alkyl radicals with 1 to 4 carbon atoms or together with the nitrogen atom a saturated heterocyclic ring, and the compounds obtained are optionally converted into salts or quaternary ammonium compounds by reaction with acids or alkyl halides. ι 909 638/377 10:59