DE2414751A1 - NEW 4H PYRIDO SQUARE CLAMP ON 1.2A SQUARE CLAMP FOR PYRIMIDINE DERIVATIVES AND METHOD OF MANUFACTURING THE SAME - Google Patents

Description

/> ~ 'V * γ ·! ;;' ¹ :. I cn /.—in

rfre ^ i? -TeUfea 5 ^ 5061 2414751

Frankfurt (Main), d. 22 Mar 1974-

Oliinoin Gyogyszer es Vegyeszeti Termekek Gyara ET., Budapest IT, Τδ utca 1-5, Hungary

NEW 4H-PYBIDO ^, 2 ^ PiRIMIDIN-DECIVATE AND METHOD OF MANUFACTURING THE SAME

The invention relates to new compounds of the general formula I.

and their salts and quaternary salts / in which
R ^{1 is} hydrogen or alkyl;

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2 '

R hydrogen, halogen, alkyl, aralkyl, amino, alkylamino, Acylamino, hydroxy, alkoxy, carboxy or a carboxylic acid derivative group means;

H ^v denotes hydrogen, carboxy or a carboxylic acid derivative group;
n = 1 or 2 /

The term "alkyl group." relates to straight-chain or branched hydrocarbon groups with 1-4 carbon atoms / eg methyl, ethyl, etc. J. The term "halogen" includes fluorine, bromine, chlorine and iodine. The alkylamino groups contain 1-7 carbon atoms. The acyl groups occurring in the acylamino groups can be derived from alkanecarboxylic acids with 1-6 carbon atoms or arylcarboxylic acids, / for example acetyl, propionyl, benzoyl, etc./. The alkoxy groups can be straight-chain or branched and contain 1-4 carbon atoms / for example methoxy, ethoxy, isopropoxy, n-butoxy /. The aralkyl groups can contain 7-9 carbon atoms / e.g. benzyl, beta-phenylethyl, etc. 7.

The term “carboxylic acid derivative group” includes the usual carboxylic acid derivatives. As a beneficial representative -of these groups the following can be mentioned: alkoxycarbonyl groups / e.g. straight-chain or branched groups

with 1-6 carbon atoms, e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isobutoxycarbonyl USW ₁ /, carbamoyl group, N-substituted carboxyl groups, e.g. N-alkylcarbamoyl or N-aralkylcarbamoyl groups, where the alkyl substituent can contain 1-6 carbon atoms and the aralkyl substituent 7-9 carbon atoms , £ e.g. methyl, ethyl, propyl,

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Butyl, benzyl, beta-phenylethyl, etc. ⁷ . The abovementioned aryl groups can be substituted by one or more alkyl, alkoxy or halogen substituents. Advantageously substituted carbamoyl groups are the N-methyl, N-ethyl and W-2- / 5 »4-dimethoxyphenyl7-ethyl-carbamoyl groups. The acid hydrazido and hydroxamic acid groups can be mentioned as further carboxylic acid derivative groups.

The salts of the compounds of the formula I can with inorganic or organic acids are formed / e.g. Hydrochloric acid, hydrogen bromide, phosphoric acid, sulfuric acid, Perchloric acid, formic acid, acetic acid, citric acid, malic acid, glutamic acid, mandelic acid, salicylic acid, etc ^ /. The quaternary salts of the compounds of formula I can be formed with the usual quaternary agents »,.

Il

e.g., alkyl halides such as methyl iodide, ethyl iodide, etc .; Dialkyl sulfates, e.g. dimethyl sulfate or alkyl or aryl benzene sulfonates, or p-ioluenesulfonates.

Particularly advantageous representatives of the compounds of the formula I are the following derivatives: 3- / carboxymethyl7-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-

-pyrido / i, 2a / pyrimidine;
3- / Carboxymethyl7-4-oxo-6,7,8,9-t-tetrahydro-4H-pyrido / i, 2a7py-

rimidin;
3- / ethoxycarbonyl-methyl7-6-methyl-4-oxo-6,7,8,9-tetrahydro-

-4H-pyrido / 1,2a / pyrimidine;
^ - // ethoxycarbonyl-methyl / ^ - oxo-e, 7,8,9-tetrahydro-4H- -pyrido / i, 2a / pyrimidine;

3- / ithoxycarbonyl-methyl7-7-iaethyl-4-oxo-6,7,8,9-tetrahydro-

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, 2a7pyrimidine;

3- / lUhoxycarbonyl-methyl7-8-methyl-4-oxo-4H-pyrido / i, 2a / py-

rimidin;
6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / L, 2a7pyrimidine- -S- ^ methyl-carbohydrazide /;

3, ö-Dimethyl - ^ - oxo-ö., 7,8,9-tetrahydro-4H-pyrido / I, 2a / pyrimidine; 3- / N-2-phenyl-ethyl7-carboxamido-methyl-6-methyl-4-oxo-6,7,8,9-

-tetrahydro-4H-pyrido / 1,2a7pyjcimidine; 3- {N-2- / 3 ^ -Dimethoxy-phenylZ-ethylJ -carboxamido-methyl-6-

-methyl-4-0X0-6,7,8,9-tetrahydro-4H-pyrido / i, 2a7pyrimidine; and their salts and quaternary salts, especially methosulphates. According to the method according to the invention, the compounds the lOrmel I and its salts and quaternary salts thereby produced that a compound of formula II

redussed

/ iiorin

R and η have the above meaning;

Ir has the same meaning as R, or for a nitro group stands;

R ^ represents carboxy or a carboxylic acid derivative group / and, if desired, in a compound thus obtained of Formula XII

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<CH ₂ ) _n -B ⁵

the R group is converted into an R group or an R group is converted into another R group and, if desired, one 30 obtained compound of formula I in an acid addition salt or quatern & res salt unconverted or released from a salt.

The reduction can advantageously be carried out by catalytic hydrogenation.

The hydrogenation takes place at a temperature of 0-100 ° G and under atmospheric or elevated pressure of 1-60 atm.

The reaction can be carried out in a solvent. The reaction medium can be water, alkanols / z.B. Methanol or ethanol /, ester / e.g. Ethyl acetate 7 ketones / e.g. Acetone or methyl-ethyl-ketone / or organic acids Use /z.jö.Essigsfe'ure/ or their mixtures. The usual hydrogenation catalysts can be used in the reaction. One can preferably use palladium Use carbon, Raney-Nikkei, platinum, or platinum oxide.

In the course of the hydrogenation, the pyridine becomes the starting material of formula II saturated by uptake of 2 moles of hydrogen. After taking in the calculated amount of hydrogen the catalyst is removed / e.g. by filtration, centrifugation, decanting / and the solvent distilled off. The resulting compounds of the formula III or their acid addition salts can, if necessary, from a

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suitable solvent are recrystallized.

If compounds of the formula II in which IT is a nitro group are used as the starting material, there is next to the saturation of the pyridine ring the reduction of the nitro. group instead and compounds of the formula III are formed in which R stands for an amino group. In the Hydrogenation of a starting material of the formula II in which R ^ is a Represents the nitro group in the presence of a solvent of the Ketone type, a reaction occurs between the amino group and the solvent leaking out under water j and ea Compounds of formula III obtained in which R is an alkylamino group. If you have a starting material of the Formula II, wherein R is nitro, in the presence of acetone as If the solvent is reduced, compounds of the formula are formed

ο
III, wherein R represents an isopropylamino group.

In a compound of the formula III obtained in this way, the R group can, if desired, be converted into the R group or a R group can be transferred to another R group. These reactions can be carried out according to methods known per se. carried out will. An AlkoxycarbonyIgruppe can by hydrolysis be converted into the carboxy group. The reaction can advantageously under alkaline conditions using alkali hydroxides / e.g. an aqueous sodium or potassium hydroxide solution / be carried out. An alkoxycarbonyl group can be converted into the acid hydrazide group with the aid of hydrazine will. The hydrazine can preferably be used as an alcoholic solution; in this reaction can both Hydrazine salts, as well as hydrazine hydrate, are used. the

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Carboxyl group can be removed by treatment with an alcohol /ÜT.B. Ethanol ^ in the presence of a solvent / eg benzene / can be converted into an alkoxycarbonyl group. The carboxyl group can be converted into an acid amide by reaction with the corresponding amine in the absence or presence of a solvent, for example xylene. The free carboxylic acids can be prepared by treatment with a Halogenidj? Ungsmitibel / for example thionyl chloride, phosphorus oxychloride, uswj ⁷ in the acid halides Überxührt be that corresponding turn by treatment with water in the free acids, or by using the corresponding alcohols in Alkoxycarbonylester or under the action of the Amines can be converted into the acid amides. Compounds of the formula I in which R is a carboxyl group can be converted into the corresponding compound of the formula I in which R 1 is hydrogen by decarboxylation. This reaction can be carried out by heating at a temperature exceeding the melting point.

The above conversions of one R ^ group to another Rr groups take place according to methods of organic chemistry known per se and customary to the person skilled in the art.

The compounds of the formula I can be known per se Way converted into their acid addition salts and quaternary salts will. The reaction can be carried out, for example, by reacting the base of the formula I with an approximately equimolar amount of the corresponding acid or the quaternary! sizing agent in Carried out in the presence of an organic solvent will. Both inorganic, Vfie and

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organic acids are suitable, e.g. hydrochloric acid, hydrogen bromide acid, phosphoric acid, sulfuric acid, perchloric acid, formic acid, acetic acid, "citric acid, mandelic acid, malic acid, Glutamic acid, salicylic acid, etc. As quaternary agents one can use alkyl halides /z. Methyl iodide, ethyl iodide /, Dialkyl sulfates / e.g. Dimethyl sulfate / or alkyl or use arylbenzenesulfonates and ρ-toluenesulfonates.

The starting materials of the formula II can be obtained by cyclizing a compound of the formula IV

A ₁ Π ^ NH - CH R ⁶ \ R ^ = C

are prepared, / in which R, R, R and η have the above meanings and R means an alkoxycarbonyl group /. The ring closure can be carried out in the presence of an inert solvent or an acidic condensing agent Jz.B. Phosphorus oxychloride, phosphorus trihalides, polyphosphoric acid, ₁ / can be carried out at a temperature between 25 ° C and 400 ° 0. The production of the starting materials is described in DOS No. 2,315,422.

The compounds of the formula I have valuable therapeutic properties and, in particular, exert analgesic, anti-inflammatory _/ antipyretic and other effects which favorably influence the central nervous system / eg narcotic or tranquillant effects, etc. "

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The invention further relates to compounds of the formula I or their salts or quaternary salts containing pharmaceutical preparations and their manufacturing processes. The pharmaceutical preparations according to the invention contain as active ingredient a compound of the formula I or their acid addition salts or quaternary salts and customary inert solid or liquid carriers and diluents, bie preparations may for example solutions, suspensions, emulsions, USW ^ / ⁷ are completed in solid / for example, tablets, dragees, capsules, suppositories / or liquid /.

Common carriers include magnesium stearate, Talc, calcium carbonate, water, polyethylene glycol, grlycerin formal use.

The preparations may contain conventional erwünsentenfalls Zusatzjaittel / Eniulgierungsmittel example, .Suspendierungsmittel, disintegrating agents, USW ₁ /.

The preparations are manufactured according to methods known per se from the pharmaceutical industry.

Further details of the process according to the invention can be found in the examples without indicating the scope of protection limit the examples.

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B EXAMPLES

1 * 7 4, 4 g / 6.02 Mol7 3- / C "arboxy ethyl _^:; 7-6-aeth.yl-4-oxo -4H-pyrido / 3L, 2a7-pyrimidine in 60 did Bisessig suspended and hydrogenated in the presence of 1.5 g of palladium-carbon catalyst under atmospheric pressure. The calculated amount of hydrogen is absorbed within 30 minutes. The catalyst is then filtered off with suction and the solution is evaporated to dryness under reduced pressure Oil / 8 * 2 $ is recrystallized from 9 ml of 96% alcohol. 3.3 g / 75 "ff of the white, melting at 193-194 ° 0 ^ -

^ H-pyrido / i _t 2a / -pyrimidins obtained. After further recrystallization, the melting point remains unchanged.

Analysis »porridge 0 59.45 $ H 6.35 i> K 12.6o 5 * gef * 0 59.81 $ H 6.22 <f» N 12.58? T 2; / 6, og / θ, 15 Mol / sodium hydroxide are dissolved in 60 ml of water. 14.4 g / 0.05 mol of the 3- / ethoxy-carbonyl- ^ ethyl7-6-methyl-4-oxo -6,7,8,9-tetrahydro -4H are added to the solution obtained in this way -py ri do / 1, 2a7-pyrimidine-hydro chlo ri ds inserted. The solution is allowed to stir for 3 hours at room temperature. The pH of the solution is then adjusted to 7 with 1: 1 hydrochloric acid / approx. 8 ml7 and the solution is decolorized with charcoal. The pH of the decolorized solution is adjusted to 4. / If the pH value is low, the acid will dissolve /. The solution is left in the refrigerator for a few hours. The precipitated crystals are filtered off with suction.

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- ii -

3.6 g / 32 # 7 of the 3- / 0 arboxyZ-methyl7 ~ 6 ~ ni9 lhyl ~ 4 -oxo-6,7 ~ 8,9 -tetrahydro -4H- ~ pyrido / l, melting at 191 ° C, 2§7pyrimidlns received. The aqueous mother liquor is evaporated. The stooping sand created in this way is dissolved in the water under heating. After cooling down, 3.5 g / 50 Ü? obtained from the acid melting at 192 ° C. The overall yield is 7.1 g / 62 ^ /. The melting point rises to 193-194 ° G after crystallization from the same volume of 96% alcohol.

Should be used as the starting substance in the above procedure the 3- / ethoxycarbonyl ~ methyl7 ~ 4-oxo-6,7,8,9-tetrahydro-4H- -pyrido / i, 2a7-pyrimidine are used, so that 3- / carboxy-methyl7-4-oxo -6,7,8,9-t etrahydro-4H-pyri do / ϊ, -pyrimidine obtained with 80 $ yield / mp. 174-175 °

3-7 53.7 g / 0.2 mol of 3- / ethoxycarbonyl-methyl7-4-oxo- -4H-pyrido- / i, 2a7-pyrimoidin hydrochloride are dissolved in 250 ml of water. After adding 10 ml of hydrochloric acid and 20 g of palladium-carbon catalyst, the substance is hydrogenated under a pressure of 5-10 atmospheres. After the calculated amount of hydrogen has been absorbed, the catalyst is suctioned off and the pH is adjusted to 7 with a 50% sodium carbonate solution / about 75 ml7.

The solution obtained in this way is decolorized with bone charcoal and filtered off. The clear filtrate is three times shaken out with 200 ml of benzene each time. The combined benzene-containing extracts are dried over sodium sulfate,

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then filtered and evaporated. 32.0 g / 68 of a crystalline substance melting at 63-66 ° C. are obtained,

Shaking out the aqueous mother liquor with ELoroform and working up the chloroform extract, a further 2.8 g / 5.5 $ of the product are obtained. Overall yield: 73.5 ffi. The substance obtained in this way is recrystallized from an anhydrous mixture of alcohol-petroleum ether, it becomes the white 3- / ethoxycarbonyl-74-0X0-6,7,8,9- tetrahydro-4H-pyrido which melts at 65-66 ° C / i, 2a7-py * "imidine. Analysis: Calculated: C 61.00 $ H 6.75 $ N 11.86 $ found : C 60.01 $ H 6.82 g N 12.02 £

If the 3- _ί / Athoxycarbonyl-methyl7-7-methyl-4-oxo- ^ H-pyrido / l ^^ - pyrimidine hydrochloride are used as the starting material, the 3- / Athoxycarbonyl-methyl7-7- -methyl- 4-oxo-6,7,8,9-tetrahydro -4H-pyrido / 1, 2a7-pyrimidine obtained with a 72% yield as a non-crystallizable oil. / M.p. HCl 146-147 ° θ / -

Should the 3- / Athoxycarbonyl-methyl7-8- ^ αethyl-4-oxo- -4H-pyrido- ^ L, 2§7pyrimidine hydrochloride used as starting material the 3- / ethoxycarbonyl-methyl7-8- -4aethyl ~ 4-oxo-4H-pyrido / I, 2a7pyrimidine with an 86 # iger Yield obtained / m.p .: 44-45 ° c7.

4 ^ 7 ° »25 g / Jtool7 3-Z5.thoxycarbonyl-methyl7-6-methyl--4-oxo-6,7,8,9-tetrahydro-4H-pyrido / i, 2a7pyrimidine are dissolved in 1 ml of anhydrous alcohol dissolved, then 0.1 ml / 2 Mmol7 ¹⁰ ° # igea hydrasin hydrate is added to the solution. After standing for one day at room temperature, the solution is evaporated to dryness and the remaining, slowly to a crystal

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«13 -

maase eraiarrende Pro dU nietert from a mixture of alcohol-ether umteilatallietert »Ka is & o 0.17 g / 72 J ^ of the ffeieaea, at 132-135 ° 0 eohmelssenden 6 ~ methyl-4-oxo-6,7,8,9- tetra ~ hydro-4-H-pyri do / ϊ, 2§7py rimiüia-3- / E ethyl-carbohydrazidj / obtained. After further recrystallization, the melting point remains unchanged.

Analysis: 0 55.91 $> H 6.83 $ N 23.72 £ gefi 0 55.20? Έ H 7.15 # N 23.69 i »

5J 25.0 g / 0.1 mol7 3 ~ / ethoxycarbonyl-methyl7-6- -methyl-4 ~ oxo-6,7,8,9-t-ethrahydro-4H-pyrido / i, 2a7pyrimidin are in 50 ml anhydrous Dissolved acetone and then 13.2 g / 5.105 Mol7 freshly distilled dimethyl sulfate is added to the solution. The solution is kept at 40 ° C. for 10 minutes, then distilled off at room temperature. During one day, the precipitated crystals are suctioned off and covered with a little anhydrous acetone. There are 21 g / 56 $ 7 of the white 3- / ethoxycarbonyl-methyl7 ~ -1,6-dimethyl-4-oxo-6,7,8,9-tetrahydro -4H-pyrido / l, melting at 150 ° 0 , 2a7pyri ~ midinium methosulfate obtained. With further recrystallization, the melting point remains unchanged. Analysis: calc: C 47.86 # H 3.75 # N 7.44 <f> S 8.52 # found: C 47.98 $> H 3.70 $> N 7.42 $ S 8.41 $ >

If the 3- / Athojtyearbonyl- ~ iiethyl7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / i, 2a7pyrimidin be used as starting material in the above Yerfahren, the 3- / Ethoxy-, carbonyl -methylZ-1-methyl ^ -oxo-e, 7,8,9-t etrahydro-4H- -pyrido / i, 2a7pyrimidinium ~ methosulfate / m.p. 141-142 ° g / obtained.

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6.7 111.1 g ^ 5.5
-oxo-6 _t 7 »8,9-tetrahydro-4H-pyriao ^ i, 2§7pyriaidiii are obtained at the oil bath until the ÖOg development has ceased. The Rttoketand is fractionated at 0.3-0.4 Hgmm. You will get 61 »5 β / §9 £ 7 of an oil which can be crystallized on cooling. The crystals obtained in this way are recrystallized from half a volume of acetone. The melting point of the white 3 »6-dimethyl-4-0x0-6,7,8,9-tetrahydro- -4H-pyriao / i, 2a7pyrimidine obtained is 73-74 ° 0. The melting point remains after further Recrystallization unchanged. Analysis about * C 67.39 $> H 7.92 i > Sf 15.72? I found 67.10 # H 8.20 $ N 15.91 # 7-7 22.2 g / 0.1 mol / 3- ^ Carboxy-methyi7-6-methyl-4-e ^ jejg-tetrahydro ^ H-pyrido / l ^ a / pyrimidine, 12.1 g, l hol / 2-phenyl-ethyl-amine and 100 ml of xylene Heated in an apparatus equipped with a water separator for 3 hours under cold flow, meanwhile 1.8 ml of water are collected in the attachment. The solution is then evaporated to dryness under reduced pressure. Bs become 32.3 g / 99 $> / of 3- / S-2-phenyl-ethyl-7-carboxamido-methyl-6-halethyl-4-oxo-6,7,8 _> 9-tetrahydro-4H-pyrido / l , 2a / pyrimidines obtained as a non-crystallizable oil. Should 3.25 g / 5.01 mol7 oil be dissolved in 3 ml alcohol and 1.5 ml 70 # perchloric acid added to the solution, 3.0 g / 71 * ff of the light yellow, at 174- 176 ° G melting 3 - / & - 2-phenyl-ethyl / - -carboxamido-methyl-eHaethyl-4-0x0-6,7,8,9-tetrahydro-4H-pyrido / i, 2a / pyrimidinium perchlorate obtained . According to TJm-

11 crystallization from eight times the amount of ethanol is the

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M.p. 176-177 ° E.

Analysis »ben 0 53.59 tf H 5.66 * N 9.87 Tf 01 8.32 * gefi 0 53.6196 H 5.65 Ji Ii 9.94 Ji 01 8.95 3 * Should be with the above. Process 2- / 3 »4-Dimethoxy-pnenyl7 · -Hthyl-amine ale amine component is used, so that 3- (K-2- / 3 »4-Dimethoxyphenyl7-fithyl) -oarboxamido-methyl-6- -methyl-4-0x0-6,7,8,9-tetrahydro-4H-pyrido / 1,2a7pyrimidine with 99% yield as a light yellow, non-crystallizable one get oil.

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Claims (1)

PATENT CLAIMS or their acid addition salts or quaternary salts,
wherein R is hydrogen or alkyl; R is hydrogen, halogen, alkyl, aralkyl, amino, alkylamino, acylamino, hydroxy, alkoxy, carboxy or a
Means carboxylic acid derivative group;
Έ. Hydrogen, carboxy or a carboxylic acid derivative group means;
η β 1 or 2. 2. 3-Z-carboxymethyl7-6-methy 1-4-oxo-6,7,8,9-tetrahydro--4H-pyrido / 1,2,7-pyrimidine;
3- / Carboxymethyl7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / 1,2§7py- rimidin;
3- ^ ithoxycarbonyl-4ttethyl7-6-aiethyi-4-oxo-6,7 »8,9-tetrahydro--4H-pyrido ^ i, 2§ / pyrimidine; 3- / ethoxycarbonyl-methyl-7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / Ϊ12a7pyrimidine;
3- / lthoxyoarbonyl-methyl7-7-methyl-4-0X0-6,7,8,9-tetrahydro- -4H-pyrido / 1,2a7pyrimidine;
3-Zlthoxycarbonyl ^ aethyl7-8-methyl-4-oxo-4H-pyrido / i, 2§7py- rimidin; 409841/1016 24U751 - 17 - 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / i, 2a7pyrimidine- 3,6-dimethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / 1,2a7pyrlmidinj
3- / S-phenyl-ethyl-7-carpoxemido-me ^1- ethyl-6Haiethyl-4-oxo- -6,7,8,9-tetrahydro-4: H-pyrido / I, 2§7pyrimldine; 3- (N-2- / 3,4-Dimethoxyphenyl7-gthyl) -oarl) OxamidOHmethyl-6- -methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / 1,2a7pyrlmidine; and their salts and quaternary salts, especially Hethosulfate. 3. Process for the preparation of compounds of the general formula I. ■ ■ 0 ' and their acid addition salts and quaternary salts / in which E ¹ , R ² , R- * and η are as in claim 1, Z characterized in that a compound of the formula II H ¹ reduced,
/wherein R ¹ and η have the above meaning} R ^{4 has} the same meaning as R ² or represents a nitro group; 409841/1016 R * represents carboxy or a carboxylic acid derivative group / and, if necessary, in a compound of the formula III obtained ao 5 ^ " ⁵ p the R group is converted into an R group or an R group is converted into another R group and, if desired, a compound of the formula I obtained in this way is converted into an acid addition salt or quaternary salt or released from a salt * 4. The method according to claim 3 »characterized in that the starting material used is a compound of the formula II in which R is hydrogen or C _1-4 alkyl. 5. The method according to any one of claims 3-4> thereby gek e η η ζ ei chnet that the starting material used is a compound of the formula II in which R is hydrogen, C _1- . Alkyl, C ₇ -g aralkyl, halogen, nitro, amino, C _1-6 alkyl-. amino, C _1-4 alkanoylamino, benzoylamino, hydroxy-C _1-4 alkoxy, carboxy, or a carboxylic acid derivative group. 6. The method according to any one of claims 3-5, characterized gekennz ei chnet that a compound of formula II is used as starting material, wherein R ^{5 is} a carboxy ', carbamoyl, N-alkyl-carbamoyl, N-phenylalkyl-earbamoyl, acid hydrazido or Cig means alkoxycarbonyl group. 409841/1016 24U751 7. Method according to claim 3. » dadur ο hg e- It shows that the reduction is carried out by catalytic hydrogenation. 8. The method according to claim 7, characterized in that the catalyst used is palladium, Raney-Mkkel, platinum * or platinum oxide are used. 9. The method according to any one of claims 3-8, characterized in that the reaction is carried out in water, an alcohol, ketone, ester in an organic acid, advantageously acetic acid or mixtures thereof . 10. The method according to claim 7 »characterized ge ζ ei chnet that the hydrogenation under atmospheric pressure or a pressure of 1-50 atm. performs. 11. A method according to claim 7, characterized e- g kennzei seframe that one carries out the hydrogenation at 0-100 °. 12. The method according to any one of claims 3-H » characterized in that the starting materials of the formula II are used in the form of the free acid or its SBureaddi tion salts. 13 · The method na "h to any of claims 3-12, characterized EKENN g ζ ei chn t e, that a bond of the formula III obtained Ver one or more of the following reactions subjecting ;. Conversion of the carboxy group into an alkoxycarbonyl group by esterification; Conversion of the carboxy group into an optionally substituted orbamoyl group by reaction with the corresponding amine; Overpass 409841/1016 the oarboxy group by reaction with a halogenating agent, advantageously thionyl chloride, into an acid halide and treatment of the acid halide obtained with ammonia into the carbamoyl group, conversion of an alkoxycarbonyl group, the carboxyl group by hydrolysis, conversion of an alkoxycarbonyl group into the acid hydrazido group by treatment with hydrazine; Conversion of an alkoxycarbonyl group into the hydroxamic acid group by treatment with hydroxylamine. 14 ·. Method according to one of Claims 3-13 »thereby gekennzei chnet that a compound of formula I with a non-toxic organic or inorganic Acid, e.g. formic acid, acetic acid, salicylic acid, mandelic acid, citric acid, hydrochloric acid, hydrobromic acid, Hydroiodic acid, perchloric acid, sulfuric acid or Phosphoric acid converts. 15. The method according to any one of claims 3-13, characterized characterized in that a compound of the formula I with alkyl halides, advantageously methyl iodide, or Ethyl chloride, or dialkyl sulfates, advantageously dimethyl sulfate or diethyl sulfate, or p-toluenesulfenic acid ester, e.g. Methyl or ethyl esters or benzenesulfonic acid esters, advantageously Il used methyl or ethyl esters. 16. Pharmaceutical preparations, characterized in that that they are a compound of formula I or their acid addition salts or as active ingredient contain quaternary salts and inert carriers. 409841 / 1U1 6 24U751 17 »Pharmaceutical preparations according to claim 16, characterized in that they contain a prepared according to claim 2. A compound of formula I as Wirkatoff. 18. Pharmaceutical preparations according to one of claims 16 and 17 in the form of tablets, coated tablets, capsules, suppositories, solutions, suspensions or emulsions. 19. Process for the production of pharmaceutical preparations, characterized in that a compound of the formula I or its acid addition salts or quaternary salts are mixed with suitable inert solid or liquid carriers. 409841/1016