DE2757503A1 - 5.6-DIHYDROBENZO SQUARE CLAMP ON 5.6 SQUARE BRACKET FOR CYCLOHEPTA SQUARE BRACKET ON 1.2-ANGLE BRACKET FOR PYRAZOLO SQUARE BRACKET ON 4.3-SQUARE BRACKET FOR -PYRIDINE-11 (1H) -ONE AND -IMINE AND THEIR SALTS AND THE USE OF THESE COMPOUNDS AS PSYCHOTROPIC AND ANTI-INFLAMMATORY DRUGS - Google Patents

Description

The invention relates to 5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -ones and -imines of the general formula I and their salts.

The invention also relates to 1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridines of the general formulas II and III and and their salts.

In the above formulas, the individual symbols have the following meanings:

R [deep] 1 denotes hydrogen, lower-alkyl, phenyl or phenyl-lower-alkyl.

R [deep] 2 denotes hydrogen, lower-alkyl or phenyl.

R [deep] 3 denotes hydroxy, halogen, lower-alkoxy or an amine group.

The amine group is either an acyclic group of the formula where R [deep] 5 and R [deep] 6 are each hydrogen, lower-alkyl or phenyl or R [deep] 5 and R [deep] 6 together with the nitrogen atom form a monocyclic, nitrogen-containing, 5- or 6-membered heterocyclic ring with optionally a further nitrogen, oxygen or sulfur atom.

R [deep] 4 is oxygen (= O) or substituted imine (= NR), where R is lower-alkyl or phenyl.

R [deep] 7 means hydrogen, halogen or lower-alkoxy.

R [deep] 8 means hydrogen, or

R [deep] 9 means hydrogen or lower-alkoxy.

R [deep] 10 means hydrogen, or n is an integer with a value from 2 to 6.

R [deep] 11 and R [deep] 12 are identical or different and each mean lower-alkyl or R [deep] 11 and R [deep] 12 form a heterocyclic ring of the formulas with the nitrogen atom to which they are bonded or

, where R [deep] 13 is hydrogen or lower-alkyl.

R [deep] 14 and R [deep] 15 independently of one another denote hydrogen or lower-alkyl or, together with the nitrogen atom to which they are bonded, form a heterocyclic ring of the formulas

or

, where R [deep] 13 has the above meaning.

Compounds of the general formula II and their pharmacologically acceptable salts are preferred, the individual symbols having the following meanings:

R [deep] 1 means lower-alkyl and especially ethyl.

R [deep] 2 means hydrogen.

R [deep] 7 denotes hydrogen, chlorine, bromine or lower-alkoxy and in particular hydrogen, chlorine or methoxy.

R [deep] 8 means hydrogen, or

, where n is an integer with a value from 2 to 4 and in particular has the value 3.

R [deep] 11 and R [deep] 12 are identical and each mean methyl or ethyl and in particular methyl.

Furthermore, compounds of the general formula III and their pharmacologically acceptable salts, in which the individual symbols have the following meanings, are preferred:

R [deep] 1 means lower-alkyl and especially ethyl.

R [deep] 2 means hydrogen.

R [deep] 9 denotes hydrogen or methoxy and especially hydrogen.

R [deep] 10 denotes a heterocyclic radical of the formulas or

, where R [deep] 13 represents hydrogen or methyl, and in particular radicals of the formulas and

Furthermore, R [deep] 10 can be a substituted amine of the formulas or mean, where R [deep] 16 is lower-alkyl, n is an integer with a value from 2 to 4 and in particular has the value 3 and R [deep] 11 and R [deep] 12 are the same and are each methyl or ethyl and in particular each represent methyl.

The compounds according to the invention, ie the substituted 5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridines and substituted 1,5,6,11-tetrahydrobenzo [5,6] Cyclohepta [1,2-b] pyrazolo [3,4-e] pyridines are valuable drugs with psychotropic and anti-inflammatory effects. After the ring system has been formed, successive or alternative treatments with various reagents, as explained in more detail below, give derivatives with the possible uses indicated.

The 5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -ones and 5,6-dihydrobenzo [5,6] cyclohepta [1, 2-b] pyrazolo [4,3-e] pyridine-11 (1H) -imines are substituted in the 1- and 4-positions and optionally in the 3-position. This class of compounds has the general formula I.

This class of compounds is characterized by two major substituents, i.e. R [deep] 4 is either oxo or a substituted imine group. These two groups of compounds can be represented by the general formulas Ia and Ib.

The substituted 1,5,6,11-tetrahydro [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridines can be prepared from compounds of the general formula Ia. These various derivatives are explained in more detail below in the description of the production processes and in the examples. All of these compounds are within the scope of the invention.

The meaning of the individual symbols is explained in more detail below:

R [deep] 1 denotes lower-alkyl, phenyl or phenyl-lower-alkyl. The expression lower-alkyl is to be understood as meaning straight-chain or branched hydrocarbon radicals with up to 7 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and pentyl. In a corresponding manner, the phenyl-lower-alkyl radicals have a phenyl substituent in the alkyl chain. In any case, alkyl radicals having 1 to 4 carbon atoms and, in particular, alkyl radicals having 1 to 2 carbon atoms are preferred.

R [deep] 2 denotes hydrogen, lower-alkyl or phenyl. The above explanations apply to lower-alkyl, radicals with 1 to 4 and in particular with 1 to 2 carbon atoms likewise being preferred.

R [deep] 3 denotes hydroxy, lower-alkoxy, halogen or an amine group of the formula

The lower alkoxy radicals correspond to the above lower alkyl radicals, the lower alkyl radicals being bonded to an oxygen atom. Examples are methoxy, ethoxy, propoxy, isopropoxy, butoxy and tert-butoxy. Correspondingly, alkoxy radicals with 1 to 4 and in particular with 1 to 2 carbon atoms are preferred. The four usual halogen atoms are suitable as halogen atoms, preferably chlorine or bromine and in particular chlorine.

With the amine residue it is an acyclic one

Amine radical in which R [deep] 5 is hydrogen, lower-alkyl or phenyl and R [deep] 6 is lower-alkyl or phenyl. R [deep] 5 and R [deep] 6 can form a monocyclic, 5- or 6-membered hetero-cyclic ring with the nitrogen atom, in which an additional hetero atom such as nitrogen, oxygen or sulfur can be present. The heterocyclic ring can optionally be substituted by lower-alkyl or hydroxy-lower-alkyl.

Examples of acyclic amines of the formula are lower-alkylamino, such as methylamino, ethylamino, propylamino, isopropylamino, butylamino and tert-butylamino, phenylamino, di- (lower-alkyl) -amino, such as dimethylamino, diethylamino, methylethylamino, dipropylamino and dibutylamino and anilino. In the case of the alkyl radicals, those with 1 to 4 and in particular with 1 to 2 carbon atoms are also preferred. Of the radicals R [deep] 5 and R [deep] 6, preferably only one is phenyl.

Examples of heterocyclic substituents of the formula are piperidino, morpholines, thiamorpholino and piperazino, which can each be substituted by lower-alkyl or hydroxy-lower-alkyl, ie these heterocyclic substituents can be represented by the formulas R [deep] 7-hetero, where "hetero" is one of the above said heterocyclic rings and in the case of unsubstituted rings R [deep] 7 is hydrogen and in the case of substituted rings R [deep] 7 is lower-alkyl or hydroxy-lower-alkyl. Preferred examples of corresponding substituted radicals are 4-methylpiperidino, 4-methylpiperazino and 4-hydroxyethylpiperazino.

R [deep] 4 means oxo (= O) or substituted imino (= NR). R denotes lower-alkyl of the type mentioned above or phenyl.

Particularly preferred are compounds of the general formula Ia in which R [deep] 1 is lower-alkyl and in particular ethyl, R [deep] 2 is hydrogen and R [deep] 3 is hydroxy, lower-alkoxy and in particular methoxy or ethoxy or lower-alkylamino and in particular means methylamino or butylamino. Also particularly preferred are compounds of the general formula Ib in which R [deep] 1 is lower-alkyl and in particular ethyl, R [deep] 2 is hydrogen, R [deep] 3 is lower-alkylamino and in particular methylamino or butylamino and R is lower-alkyl and in particular denotes methyl or butyl.

The compounds of the invention can be prepared according to the following reaction sequences.

A 5-aminopyrazole of the general formula IV

(prepared according to Zf Chemie, Vol. 10 (1970), pp. 386 to 388) is with a 2- (2-phenylethyl) -acetoacetic acid ester of the general formula V

(prepared according to Annalen der Chemie, Vol. 395 (1913), p. 95) with heating to a temperature of about 140 ° C. in the presence of polyphosphoric acid to form a compound of the general formula VI implemented.

The intermediate of the general formula VI is oxidized with an oxidizing agent such as selenium dioxide in a solvent such as diethylene glycol dimethyl ether or pyridine at about 140 ° C to a compound of the general formula VII, which in most cases, in addition to unreacted starting compound of the general formula VI, also contains an aldehyde of the general formula VIII

contains as impurities. Both compounds can be separated off by customary methods. The methyl compound of the general formula VI can be reused in the oxidation stage, while the aldehyde of the general formula VIII is converted by H [deep] 2O [deep] 2 in acetic acid to the acid of the general formula VII.

The compound of the general formula VII is then reacted with heating to about 210 ° C. using polyphosphoric acid as a ring-closing agent, whereby a compound of the general formula IX receives.

The tetracyclic heterocycle of the general formula IX becomes a compound of the general formula X with an inorganic acid chloride or bromide, such as phosphorus oxychloride or thionyl chloride in which X is chlorine or bromine, reacted.

By treating the compound of the general formula X with a primary amine of the general formula XI an amino derivative of the general formula XII is obtained that with aqueous acid, such as sulfuric acid, to form a compound of the general formula XIII

can be hydrolyzed.

If a compound of the general formula X is combined with a secondary amine of the general formula XIV implemented, a product of the general formula XV is obtained

Compounds in which R [deep] 3 is lower-alkoxy, corresponding to the general formula XVI

in which R [deep] 7 denotes lower-alkyl, are prepared by alkylating the hydroxy derivatives of the general formula IX with a lower alkyl halide in the presence of a base such as potassium carbonate. The chloride or bromide is preferably used as the halide. Another possibility is to treat a compound of the general formula X with a corresponding alcoholate, for example a metal alcoholate such as sodium ethylate or potassium methylate. In this way you get the same product.

Compounds of the general formula II in which R [deep] 7 is halogen or lower-alkoxy and R [deep] 8 or means are by reacting a ketone of the general formula Ia

in which R [deep] 1 and R [deep] 2 have the above meaning and R [deep] 3 is halogen or lower-alkoxy, with a Grignard reagent of the general formulas XVII or XVIII in an inert solvent such as diethyl ether or tetrahydrofuran. The reaction is preferably carried out by heating to a temperature of about the reflux temperature for about 3 to about 8 hours.

Compounds of the general formula II in which R [deep] 7 is hydrogen and R [deep] 8 or means, can be prepared by catalytic hydrogenation of the corresponding compound of the general formula II, in which R [deep] 7 is halogen and preferably chlorine, with palladium-on-activated carbon with removal of the 4-halogen substituent.

Compounds of the general formula II in which R [deep] 7 is halogen or lower-alkoxy and R [deep] 8 is hydrogen, are prepared by reducing a ketone of the general formula Ia, for example by reaction with an aluminum alcoholate and the corresponding alcohol, such as aluminum isopropylate and

Isopropanol, or by catalytic hydrogenation of the ketone of the general formula Ia, for example with treatment for several hours with palladium-on-charcoal at around room temperature.

Compounds of the general formula II, in which both R [deep] 7 and R [deep] 8 are hydrogen, are obtained by catalytic hydrogenation of a ketone of the general formula Ia, in which R [deep] 3 is halogen and preferably chlorine, for several hours Treatment with palladium-on-activated carbon at elevated temperatures, for example from about 50 to about 55 ° C.

Compounds of the general formula II in which R [deep] 7 is lower alkoxy and R [deep] 8 is hydrogen, can also be prepared by a ketone of the general formula Ia in which R [deep] 3 is halogen, in reduced in a single stage and reacted with an alcohol, for example by treating the ketone with sodium and an alcohol such as butanol.

By treating a compound of the general formula II, in which R [deep] 7 is hydrogen or lower-alkoxy and R [deep] 8 is hydrogen, with gaseous hydrogen chloride in the presence of calcium chloride, an intermediate of the general formula XIX is obtained

By treating the 11-chloro intermediate of the general formula XIX with an amine of the general formula XX or XXI compounds of the general formula III are obtained in which R [deep] 10 or means.

Compounds of the general formula III, in which R [deep] 9 is lower-alkoxy and R [deep] 10 is hydrogen, or means, through several hours of catalytic hydrogenation of a compound of the general formula II in which R [deep] 7 is lower-alkoxy and R [deep] 8 is hydrogen, or

means made with palladium-on-charcoal at room temperature.

Compounds of the general formula III, in which R [deep] 9 is hydrogen and R [deep] 10 is hydrogen, or means, by catalytic hydrogenation of a corresponding compound of the general formula II, in which R [deep] 7 is hydrogen or halogen and R [deep] 8 is hydrogen, or means manufactured.

The compounds of the general formulas I, II and III form salts, which are also the subject of the invention. These salts include salts with acids and, in particular, non-toxic, physiologically acceptable salts. These salts are prepared by reaction with one or more equivalents of any inorganic or organic acid which will give acid addition salts. Examples are hydrohalides, especially hydrochlorides and hydrobromides, sulfates, nitrates, borates, phosphates, oxalates, tartrates, maleates, citrates, acetates, ascorbates, succinates and aryl or alkanesulfonates, such as benzenesulfonates, methanesulfonates, cyclohexanesulfamates or toluenesulfonates. The formation of salts with acids is often a convenient way of isolating the products, for example by forming and precipitating a salt, which does not necessarily have to be non-toxic, in an appropriate medium in which the salt is insoluble. After the salt has been separated off and neutralized with a base such as barium hydroxide or sodium hydroxide, a free base of the general formula I is obtained. Other salts can then are formed from the free base by reaction with one or more equivalents of an acid which contains the desired anion.

Certain compounds of the general formula I, in which R [deep] 3 is hydroxy, form salts with metals, for example with alkali metals such as sodium and potassium, or with alkaline earth metals such as calcium and magnesium. R [deep] 3 in this case means -O-Met-, Met being a metal ion. The alkali metals, especially sodium and potassium, are preferred. These salts can be used to form soluble derivatives or as intermediates.

Further experimental details emerge from the examples.

The compounds of the invention are valuable drugs with anti-inflammatory properties. The anti-inflammatory effect can be determined by the carageenin edema test in rats.

The compounds of the invention can also be used in the treatment of anxiety and tension states.

The compounds of the invention can be processed into the manufacture of medicinal preparations such as tablets, capsules or elixirs for oral administration or sterile solutions or suspensions for parenteral administration.

The compounds of the general formulas I, II or III or their physiologically compatible salts are processed into unit doses together with physiologically compatible carriers, binders, preservatives, stabilizers, flavorings and the like according to standard pharmacological practice. The amount of active ingredient in these medicinal preparations is chosen so that the above-mentioned dosage range results.

The examples illustrate the invention. These examples also serve as models for the preparation of other compounds of the invention which can be obtained using appropriate starting materials.

example 1

1-Ethyl-5,6-dihydro-4-hydroxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

a) 1-Ethyl-6-methyl-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridin-4-ol

33 g (0.3 mol) of 5-amino-1-ethylpyrazole in 310 g of polyphosphoric acid are heated to 80 ° C. (bath temperature). This mixture is mixed with 70.5 g (0.3 mol) of 2- (2-phenylethyl) -acetoacetic acid ethyl ester with stirring. The bath temperature is increased to 100 ° C and the temperature of the solution increases to about 130 ° C. As soon as the reaction temperature begins to drop, the bath temperature is increased to 140 ° C. and maintained for 45 minutes. After the mixture has cooled to room temperature, 650 ml of water are added in portions. Stirring continues until the polyphosphoric acid has dissolved. The aqueous phosphoric acid solution is then decanted. The undissolved residue is treated with 400 ml of 5 percent aqueous ammonia to neutralize the mixture. The mixture is then extracted with chloroform. The chloroform extract is washed with water and dried over Na [deep] 2SO [deep] 4. After the addition of diethyl ether, 37 g (44 percent of theory) of 1-ethyl-6-methyl-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridin-4-ol with a melting point of 251 fall up to 256 ° C. After recrystallization from ethanol, the temperature rises to 258 to 260 ° C.

b) 1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxylic acid and 1-ethyl-4-hydroxy-5- (2-phenylethyl) - 1H-pyrazolo [3,4-b] pyridine-6-carboxaldehyde hydrochloride (1: 1)

A suspension of 45 g (0.16 mol) of 1-ethyl-6-methyl-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridin-4-ol in 300 ml of anhydrous pyridine is under Stir with 44 g thoroughly powder added selenium dioxide. The mixture is then heated to 130 to 140 ° C. (bath temperature) for 15 hours. After cooling, the precipitated selenium is filtered off and the filtrate is evaporated under reduced pressure. The remaining oil is stirred with 400 ml of water and 400 ml of diethyl ether, 16 g of the starting material being precipitated. The aqueous solution is then separated from the diethyl ether, treated with activated charcoal and acidified with half-concentrated aqueous hydrochloric acid. The precipitated 1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxylic acid is filtered off and over P [deep] 2O [deep] 5 in a desiccator and then dried at 100 ° C in a drying cabinet. 11.7 g (23.5 percent of theory) of product with a melting point of 250 to 251 ° C. (ethanol) are obtained.

The separated ether solution is treated with activated charcoal and dried over Na [deep] 2SO [deep] 4. After adding a solution of hydrogen chloride in diethyl ether, the hydrochloride of 1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxaldehyde precipitates in a yield of 9.2 g (17 percent of theory). M.p. 255-257 ° C (dec.) (Acetonitrile).

After recrystallization of the carboxaldehyde from ethanol, the acetal 6- (diethoxymethyl) -1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine hydrochloride (1: 1) is obtained from 160 to 162 ° C (acetic acid ethyl ester / anhydrous ethanol).

c) 1-Ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxylic acid from carboxaldehyde

16.5 g (0.05 mol) of 1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxaldehyde hydrochloride (1: 1) are added to Dissolve 150 ml of boiling glacial acetic acid. The filtered

The solution is cooled to about 30 ° C. and 10 g (0.1 mol) of H [deep] 2O [deep] 2 (35 percent) are added in 2 portions. The mixture is left to stand at room temperature for 20 hours. The crystallized 1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxylic acid is filtered off and washed with acetic acid and diethyl ether. 10.1 g (65 percent of theory) of product with a melting point of 250 to 251 ° C. (ethanol) are obtained.

d) 1-Ethyl-5,6-dihydro-4-hydroxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

12.4 g (0.04 mol) of 1-ethyl-4-hydroxy-5- (2-phenylethyl) -1H-pyrazolo [3,4-b] pyridine-6-carboxylic acid and 150 g of polyphosphoric acid are stirred for 30 minutes heated to 200 to 210 ° C (bath temperature). After the mixture has cooled to room temperature, 300 ml of water are slowly added with stirring until the polyphosphoric acid has completely dissolved. The remaining 1-ethyl-5,6-dihydro-4-hydroxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one is dissolved in chloroform. The extract is washed twice with water, dried over Na [deep] 2SO [deep] 4 and then evaporated under reduced pressure. 9 g (77 percent of theory) of product with a melting point of 190 to 192 ° C. are obtained. Recrystallization from ethanol increases the melting point to 195 to 197 ° C.

Example 2

4-Chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

41 g (0.14 moles) of 1-ethyl-5,6-dihydro-4-hydroxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one from Example 1 and 350 ml of phosphorus oxychloride are refluxed for 4½ hours. After cooling, the solution becomes filtered off and the excess phosphorus oxychloride removed under reduced pressure. The residue is treated with water and extracted with chloroform. The chloroform extract is washed twice with water, dried over Na [deep] 2SO [deep] 4 and treated with activated charcoal. After evaporation under reduced pressure, 38 g (87 percent of theory) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3- e] pyridin-11 (1H) -one with a melting point of 156 to 159 ° C (recrystallized from ethanol).

Example 3

4-Ethoxy-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

6.2 g (0.02 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11 (1H) -on are added to a solution of 0.5 g (0.022 mol) of sodium in 150 ml of anhydrous ethanol. The mixture is heated to 120 ° C. (bath temperature) in an autoclave for 4 hours. After cooling, the crystallized 4-ethoxy-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one is filtered off and washed with water. The yield is 3.5 g. A further 2.1 g of product are obtained by working up the mother liquor. The total yield is 5.6 g (87.5 percent of theory). The product has a temperature of 150 to 152 ° C (recrystallized from ethanol).

Example 4

1-Ethyl-5,6-dihydro-4-methoxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

If sodium methylate is used instead of sodium ethylate in the process of Example 3, 1-ethyl-5,6-dihydro-4-methoxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine 11 (1H) -one with a temperature of 197 to 200 ° C (anhydrous ethanol) in one

Yield of 73 percent of theory

Example 5

1-Ethyl-1,5,6,11-tetrahydro-N-methyl-11- (methylimino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-4- amine

7.7 g (0.025 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one and 100 ml of an alcoholic methylamine solution (127 g / liter) are heated to 150 ° C. (bath temperature) in an autoclave for 5.5 hours. After cooling, the solution is filtered off. The residue obtained after evaporation under reduced pressure is treated with water and collected. The product is then agitated in diethyl ether to dissolve the starting material. The purified 1-ethyl-1,5,6,11-tetrahydro-N-methyl-11- (methylimino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine- 4-amine is washed with water and then with diethyl ether and then dried over P [deep] 2O [deep] 5 in a desiccator. 6.2 g (78 percent of theory) of product with a melting point of 233 ° to 235 ° C. (acetone) are obtained.

Example 6

1-Ethyl-5,6-dihydro-4- (methylamino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

6.4 g (0.02 mol) of 1-ethyl-1,5,6,11-tetrahydro-N-methyl-11- (methylimino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [ 4,3-e] pyridin-4-amine in 60 ml of aqueous sulfuric acid (30 percent) are heated to 80 ° C. (bath temperature) with stirring for 8 hours. 40 ml of water are then added to the solution. The mixture is treated with activated charcoal, filtered off and neutralized by the dropwise addition of concentrated aqueous ammonia with external cooling. The precipitated 1-ethyl-5,6-dihydro-4- (methylamino) -benzo [5,6] cyclohepta [1,2-b] - Pyrazolo [4,3-e] pyridin-11 (1H) -one is stirred until the compound becomes crystalline. 5.5 g (90 percent of theory) of product with a melting point of 207 ° to 209 ° C. (anhydrous ethanol) are obtained.

The hydrochloride is prepared by dissolving the product in diethyl ether and adding a solution of hydrogen chloride in diethyl ether with stirring.

Example 7

N-Butyl-11- (butylimino) -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-4-amine

10.8 g (0.035 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one and 100 ml of butylamine are reacted according to Example 5 in an autoclave. 9.8 g (70 percent of theory) of product with a melting point of 124 to 125 ° C. (diethyl ether, refrigerator) are obtained.

Example 8

4- (Butylamino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

7.2 g (0.018 mol) of N-butyl-11- (butylimino) -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3- e] pyridin-4-amine and 100 ml of aqueous sulfuric acid (30 percent) are reacted according to Example 6. 4.7 g (75 percent of theory) of product with a melting point of 181 to 183 ° C. (ethyl acetate / diethyl ether) are obtained.

Example 9

4-Butoxy-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

When using sodium butoxide instead of sodium ethylate the procedure of Example 3 gives 4-butoxy-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 10

1-Benzyl-5,6-dihydro-4-hydroxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

When using 5-amino-1-benzylpyrazole instead of 5-amino-1-ethylpyrazole in the process of Example 1, 1-benzyl-5,6-dihydro-4-hydroxybenzo [5,6] cyclohepta [1,2- b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 11

1-Benzyl-4-bromo-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Treatment of the product of Example 10 according to the procedure of Example 2 using phosphorus oxybromide in place of phosphorus oxychloride gives 1-benzyl-4-bromo-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [ 4,3-e] pyridin-11 (1H) -one.

Example 12

1-Benzyl-4-propoxy-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Treatment of the product of Example 11 according to the procedure of Example 3 using sodium propylate in place of sodium ethylate gives 1-benzyl-4-propoxy-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [ 4,3-e] pyridin-11- (1H) -one.

Example 13

1-Methyl-3-phenyl-4-hydroxy-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

When using 5-amino-1-methyl-3-phenylpyrazole instead of 5-amino-1-ethylpyrazole in the process of Example 1, 1-methyl-3-phenyl-4-hydroxy-5,6-dihydrobenzo [5, 6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 14

4-methylamino-1-phenyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

If 5-amino-1-phenylpyrazole is used instead of 5-amino-1-ethylpyrazole in the process of Example 1, followed by the procedure of Examples 2, 3, 5 and 6, 4-chloro-1-phenyl-5,6 is obtained -dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one, 4-ethoxy-1-phenyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one, 1-phenyl-1,5,6,11-tetrahydro-N-methyl-11- (methylimino) benzo [ 5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-4-amine or 4-methylamino-1-phenyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2 -b] Pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 15

1-Benzyl-4- (phenylamino) -5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

When using 1-benzyl-4-bromo-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one of Example 11 in the procedure of Example 5 using aniline instead of methylamine and with further reaction according to Example 6, 1-benzyl-1,5,6,11-tetrahydro-

N-phenyl-11- (phenylimino) benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-4-amine and 1-benzyl-4- (phenylamino) -5, respectively , 6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 16

4- (Diethylamino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Using diethylamine instead of methylamine in the procedure of Example 5 gives 4- (diethylamino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 17

4-piperidino-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

If piperidine is used instead of methylamine in the process of Example 5, 4-piperidino-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine 11 (1H) -one.

Example 18

4- (4-Methylpiperazino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

If 1-methylpiperazine is used instead of methylamine in the process of Example 5, 4- (4-methylpiperazino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4, 3-e] pyridin-11 (1H) -one.

Example 19

1-Phenylethyl-5,6-dihydro-4- (methylamino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Using 5-amino-1-phenylethylpyrazole instead of 5-amino-1-ethylpyrazole in the procedure of Example 1 and further following the procedures of Examples 2, 3, 5 and 6 gives 4-hydroxy-1-phenylethyl-5 , 6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one, 4-chloro-1-phenylethyl-5,6-dihydrobenzo [5, 6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one, 4-ethoxy-1-phenylethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2 -b] pyrazolo [4,3-e] pyridin-11 (1H) -one, N-methyl-1-phenylethyl-1,5,6,11-tetrahydro-11- (methylimino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-4-amine or 1-phenylethyl-5,6-dihydro-4- (methylamino) benzo [5,6] cyclohepta [1,2 -b] Pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 20

1,3-Dimethyl-5,6-dihydro-4- (ethylamino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

When using 5-amino-1,3-dimethylpyrazole instead of 5-amino-1-ethylpyrazole in the procedure of Example 1 and then following the procedures of Examples 2, 5 and 6, using ethylamine instead of methylamine in the procedure of Example 5 is used, 1,3-dimethyl-4-hydroxy-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one is obtained, 4-chloro-1,3-dimethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one, 1,3-dimethyl -4-ethoxy-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one,

1,3-Dimethyl-N-ethyl-1,5,6,11-tetrahydro-11- (ethylimino) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin4- amine or 1,3-dimethyl-5,6-dihydro-4- (ethylamino) benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11 (1H) - on.

Example 21

1-Benzyl-4- (dimethylamino) -5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Using the product of Example 11 in the procedure of Example 5 and using dimethylamine in place of methylamine gives 1-benzyl-4- (dimethylamino) -5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 22

4- (4-Methylpiperidino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

If 4-methylpiperidine is used instead of methylamine in the process of Example 5, 4- (4-methylpiperidino) -1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4, 3-e] pyridin-11 (1H) -one.

Example 23

1-Benzyl-4- (morpholino) -5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Using the product of Example 11 in the procedure of Example 5 and using morpholine in place of methylamine gives 1-benzyl-4- (morpholino) -5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 24

1-Ethyl-4-thiamorpholino-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one

Using thiamorpholine instead of methylamine in the procedure of Example 5 gives 1-ethyl-4-thiamorpholino-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine 11 (1H) -one.

Example 25

1-Ethyl-4- [4- (2-hydroxyethyl) piperazino] 5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11 (1H) - on

If 4- (2-hydroxyethyl) piperazine is used instead of methylamine in the process of Example 5, 1-ethyl-4- [4- (2-hydroxyethyl) piperazino] 5,6-dihydrobenzo [5,6] cyclohepta is obtained [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one.

Example 26

4-chloro-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol

20.2 g (0.065 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one of Example 2 and 13 g (0.13 mol) of triethylamine are dissolved in 400 ml of ethyl acetate and 75 ml of anhydrous ethanol and hydrogenated catalytically at room temperature in the presence of 2 g of palladium-on-activated carbon (10 percent). The theoretical amount of hydrogen is absorbed in about 6 hours. The catalyst is then filtered off. The residue obtained after evaporation of the filtrate under reduced pressure is extracted with 200 ml of diethyl ether. The ether extract is washed with water and dried over Na [deep] 2SO [deep] 4. The product obtained after removing the ether is recrystallized from petroleum ether (60 to 70 ° C.).

12.7 g (62.5 percent of theory) of 4-chloro-1-ethyl-1,5,6,11-tetrahydro [5,6] cyclohepta [1,2-b] pyrazolo [4, 3-e] pyridin-11-ol, mp 128-130 ° C.

Example 27

1-Ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol

9.3 g (0.03 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11 (1H) One of Example 2 and 3.6 g (0.036 mol) of triethylamine are dissolved in 150 ml of anhydrous ethanol and 100 ml of ethyl acetate. Then 1 g of palladium on activated carbon (10 percent) is added. The mixture is hydrogenated at 50 to 55 ° C and a hydrogen pressure of 3 atmospheres. After the theoretical amount of hydrogen has been absorbed (about 8 hours), the catalyst is filtered off. The material obtained after evaporation of the filtrate under reduced pressure is treated with water, filtered off and dried over phosphorus pentoxide in a desiccator. 7.2 g (86 percent of theory) of 1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine 11-ol with a melting point of 130 to 132 ° C (hexane / cyclohexane = 8: 2, refrigerator).

Example 28

4-Ethoxy-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol

By hydrogenating 4-ethoxy-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -one from Example 3 according to Example 26 gives 4-ethoxy-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol.

Examples 29 to 38

According to Example 26, the products indicated in column II are obtained using the compounds indicated in column I which are substituted in the 4 position.

Example 39

4-Butoxy-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol

12.4 g (0.04 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11 (1H) -on from Example 2 are added to a solution of 2.5 g (0.11 mol) of sodium in 130 ml of butanol. The mixture is heated to 130 ° C. (bath temperature) in an autoclave for 6 hours. After cooling, the mixture is evaporated under reduced pressure. The residue is treated with diethyl ether. The undissolved material is filtered off, washed with water and recrystallized from ethanol. 7.1 g (51 percent of theory) of 4-butoxy-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3- e] pyridin-11-ol, mp 163-165 ° C.

Example 40

4-Chloro-11- [3- (dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol hydrochloride (1: 1)

12.3 g (0.1 mol) of freshly distilled and absolutely anhydrous 3- (dimethylamino) propyl chloride are slowly added to 2.4 g of magnesium turnings in 70 ml of anhydrous tetrahydrofuran with stirring and moderate heating. An iodine crystal and a few drops of ethyl iodide are used as the initiator. After all of the 3- (dimethylamino) propyl chloride has been added, the reaction mixture is refluxed for 2 to 3 hours. This Grignard reagent is treated with a solution of 10.8 g (0.035 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e ] pyridin-11 (1H) -one from Example 2 in 70 ml of anhydrous tetrahydrofuran offset. The mixture is refluxed for 5 hours and the solvent is evaporated. The residue obtained is mixed with 150 ml of water and 60 ml of a 20 percent ammonium chloride solution. The mixture is extracted with diethyl ether. The ether extract is washed with water and dried over Na [deep] 2SO [deep] 4. The ethereal solution is then left to stand in the refrigerator overnight, 2.6 g of unreacted starting product separating out in the form of an oil. The decanted solution is treated with activated charcoal, filtered and treated with 8 ml of a solution of hydrogen chloride in diethyl ether (195 g / liter). The mixture is then stirred for 40 minutes. The precipitated hydrochloride is filtered off, washed with diethyl ether and recrystallized from ethyl acetate / diethyl ether (1: 5). 8.3 g (55 percent of theory) of 4-chloro-11- [3- (dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydro [5,6] cyclohepta [ 1,2-b] Pyrazolo [4,3-e] pyridin-11-ol hydrochloride (1: 1), mp 172-176 ° C (dec.).

Example 41

11- [3- (Dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydro-4-methoxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol hydrochloride (1: 2)

A Grignard reagent is prepared from 5 g (0.21 mol) of magnesium turnings, 150 ml of anhydrous tetrahydrofuran and 25.8 g of 3- (dimethylamino) propyl chloride. This Grignard reagent is mixed with a solution of 21.5 g (0.07 mol) of 1-ethyl-5,6-dihydro-4-methoxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3 -e] pyridin-11 (1H) -one from Example 4 is added to 300 ml of anhydrous tetrahydrofuran. It is implemented and worked up according to Example 40. After recrystallization from hexane 15 g (54.5 percent of theory) of 11- [3- (dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydro-4-methoxybenzo [5,6] cyclohepta [ 1,2-b] Pyrazolo [4,3-e] pyridin-11-ol, mp 103-106 ° C.

This material is dissolved in anhydrous diethyl ether and treated with a solution of hydrogen chloride in diethyl ether. 11- [3- (Dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydro-4-methoxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3- e] pyridin-11-ol hydrochloride (1: 2), mp 106-108 ° C.

Example 42

4-chloro-1-ethyl-1,5,6,11-tetrahydro-11- (1-methyl-4-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3- e] pyridin-11-ol hydrochloride (1: 2)

A Grignard reagent is prepared from 7.2 g (0.3 mol) of magnesium turnings, 230 ml of anhydrous tetrahydrofuran and 40 g (0.3 mol) of 4-chloro-1-methylpiperidine. This Grignard solution is mixed with 31 g (0.1 mol) of 4-chloro-1-ethyl-5,6-dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine 11 (1H) -one from Example 2, dissolved in 230 ml of anhydrous tetrahydrofuran, is added. The reaction and work-up are carried out according to Example 40. 4-chloro-1-ethyl-1,5,6,11-tetrahydro-11- (1-methyl-4-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4, 3-e] pyridin-11-ol with a melting point of 130 to 132 ° C (hexane, refrigerator).

This material is dissolved in anhydrous diethyl ether and treated with a solution of hydrogen chloride in diethyl ether. 21 g of 4-chloro-1-ethyl-1,5,6,11-tetrahydro-

11- (1-methyl-4-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol hydrochloride (1: 2) of m.p. 210 up to 212 ° C (decomp.).

Example 43

1-Ethyl-1,5,6,11-tetrahydro-4-methoxy-11- (1-methyl-4-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3- e] pyridin-11-ol hydrochloride (1: 1)

The procedure is as in Example 42, but using 1-ethyl-5,6-dihydro-4-methoxybenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11 (1H) - on from Example 4 instead of the 4-chloro compound. 1-Ethyl-1,5,6,11-tetrahydro-4-methoxy-11- (1-methyl-4-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4, 3-e] pyridin-11-ol with a temperature of 90 to 93 ° C and its hydrochloride (1: 1) with a temperature of 217 to 220 ° C (decomp.) (Ethyl acetate).

Examples 44 to 67

According to Example 40, the end products of column III are obtained using the compounds listed in column I and the Grignard reagents listed in column II.

<Table> <Table>

Example 68

11- [3- (Dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11- ol hydrochloride (1: 2) hydrate (1: 1)

8 g of triethylamine and 1 g of palladium-on-activated carbon (10 percent) are added to a solution of 8.6 g (0.02 mol) of 4-chloro-11- [3- (dimethylamino) propyl] -1-ethyl 1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol hydrochloride (1: 1) from Example 40 in 200 ml of anhydrous ethanol given. The mixture is hydrogenated for 8 hours at a hydrogen pressure of 2.5 to 3 atmospheres at 45 to 50 ° C. After the catalyst has been filtered off, the alcohol is distilled off and the oil obtained is extracted with diethyl ether. The ether extract is washed with 100 ml of water, treated with activated charcoal and dried over Na [deep] 2SO [deep] 4. The residue a solution of 4.5 ml of a solution of hydrogen chloride in diethyl ether (195 g / liter) is added. The precipitate obtained is filtered off, washed with diethyl ether and dried. 7.1 g (78 percent of theory) 11- [3- (dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2- b] pyrazolo [4,3-e] pyridin-11-ol hydrochloride (1: 2) with a melting point of 102 to 104 ° C. (decomp.) (ethyl acetate / diethyl ether = 1: 4).

In a similar manner, the 4-halogen compounds listed in column III of Examples 44 to 67 can be hydrogenated according to the method described above, whereby the corresponding compounds are obtained in which R [deep] 7 is hydrogen.

Example 69

N-Butyl-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11-amine hydrochloride (1: 1)

a) 11-Chloro-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine

6 g of powdered CaCl [deep] 2 are stirred into a solution of 11 g (0.04 mol) of 1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-ol from Example 27 was added to 175 ml of anhydrous benzene. The suspension is saturated with anhydrous hydrogen chloride at room temperature for 15 hours. After standing overnight, the mixture is filtered off and the benzene evaporated under reduced pressure. The residue is extracted with diethyl ether, treated with activated charcoal and left to stand in the refrigerator. 8.3 g of 11-chloro-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine with a melting point of 107 bis crystallize 110 ° C (diethyl ether). b) N-Butyl-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11-amine hydrochloride (1: 1)

11.8 g (0.04 mol) of 11-chloro-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine of Section a) and 75 ml of butylamine are refluxed for 5 1/2 hours. After the excess butylamine has been evaporated, the residue is extracted by shaking with 100 ml of water and 100 ml of diethyl ether. The separated ether solution is washed twice with 50 ml of water, treated with activated charcoal, dried over Na [deep] 2SO [deep] 4 and then evaporated. 8.7 g of oil are obtained. This material is dissolved in 125 ml of ethyl acetate. The solution is mixed with 5 ml of a solution of hydrogen chloride in diethyl ether (195 g / liter). 8.4 g of N-butyl-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-amine hydrochloride (1: 1) with a temperature of 231 to 233 ° C (decomp.).

Example 70

N- [3- (Dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11- amine hydrochloride (1: 2) hydrate (1: 2)

11.8 g (0.04 mol) of 11-chloro-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine of Example 69 (a) and 75 ml of 3- (dimethylamino) propylamine are heated to 120 to 125 ° C. (bath temperature) for 5 1/2 hours. Following the procedure of Example 69 (b), 11 g (76 percent of theory) of oily N- [3- (dimethylamino) propyl] -1-ethyl-1,5,6,11-tetrahydrobenzo [5, 6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11-amine. After treatment with a solution of hydrogen chloride in diethyl ether, N- [3- (dimethylamino) - propyl] -1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine-11-amine hydrochloride (1: 2) - hydrate (1: 2) with a melting point of 125 ° C (decomp.).

Example 71

1-Ethyl-1,5,6,11-tetrahydro-11- (1-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine hydrochloride (1: 1)

The procedure is as in Example 70, but piperidine is used instead of 3- (dimethylamino) propylamine. Oily 1-ethyl-1,5,6,11-tetrahydro-11- (1-piperidinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine is obtained. After treatment with a solution of hydrogen chloride in diethyl ether, 1-ethyl-1,5,6,11-tetrahydro-11- (1-piperidinyl) benzo [5,6] cyclohepta [1,2-b] pyrazolo [4 , 3-e] pyridine hydrochloride (1: 1), mp 116 ° C (dec.).

Example 72

1-ethyl-1,5,6,11-tetrahydro-11- (4-methyl-1-piperazinyl) -benzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine- hydrochloride (1: 2)

7.4 g (0.025 mol) of 11-chloro-1-ethyl-1,5,6,11-tetrahydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridine from Example 69 (a) and 20 ml of N-methylpiperazine in 60 ml of benzene are refluxed for 5 1/2 hours. Following the procedure of Example 69 (b), 8.1 g of 1-ethyl-1,5,6,11-tetrahydro-11- (4-methyl-1-piperazinyl) benzo [5,6] cyclohepta [1 , 2-b] pyrazolo [4,3-e] pyridine hydrochloride (1: 2), mp 214 to 216 ° C (decomp.) (Ethyl acetate).

Examples 73 to 94

Following the procedure of Example 69, using the compounds listed in column I and column II, the products indicated in column III are obtained.

<Table>

Examples 95 to 116

The procedure is as in Example 70, but the compounds listed in column I and column II are used. The products indicated in column III are obtained.

<Table>

Examples 117 to 130

Obtained by halogenation of the compounds listed in column I with treatment with CaCl [deep] 2 according to Example 69 (a) and subsequent hydrogenation with treatment with palladium-on-activated carbon (10 percent) at 60 ° C. and a hydrogen pressure of about 3 atmospheres the products indicated in column II.

Claims (36)

1. 5,6-Dihydrobenzo [5,6] cyclohepta [1,2-b] pyrazolo [4,3-e] pyridin-11 (1H) -ones and -imines of the general formula I in the R [deep] 1 is lower-alkyl, phenyl or phenyl-lower-alkyl, R [deep] 2 is hydrogen, lower-alkyl or phenyl, R [deep] 3 hydroxyl, lower-alkoxy, halogen or the remainder denotes where R [deep] 5 is hydrogen, lower-alkyl or phenyl and R [deep] 6 is lower-alkyl or phenyl, or the remainder represents a piperidino, piperazino, morpholino or thiamorpholino group optionally substituted by a lower alkyl or hydroxyalkyl radical, and R [deep] 4 denotes oxo, lower-alkylimino or phenylimino, and their salts. 2. Compounds according to claim 1, characterized in that R [deep] 1 lower-alkyl, R [deep] 2 hydrogen, R [deep] 3 hydroxy, lower-alkoxy or lower-alkylamino and R [deep] 4 oxo or lower -Alkylimino means, as well as their salts with acids. 3. Compounds according to claim 1, characterized in that R [deep] 4 is oxo. 4. Compounds according to claim 1, characterized in that R [deep] 4 is lower-alkylimino. 5. Compounds according to claim 1, characterized in that R [deep] 3 denotes lower-alkylamino. 6. Compounds according to claim 1, characterized in that R [deep] 3 is lower-alkoxy. 7. Compounds according to claim 1, characterized in that R [deep] 3 is hydroxy. 8. Compounds according to claim 1, characterized in that R [deep] 1 is lower-alkyl and R [deep] 2 is hydrogen. 9. Compounds according to claim 1, characterized in that R [deep] 1 is ethyl and R [deep] 2 is hydrogen. 10. Compounds according to claim 9, characterized in that R [deep] 3 is hydroxy and R [deep] 4 is oxo. 11. Compounds according to claim 9, characterized in that R [deep] 3 is chlorine and R [deep] 4 is oxo. 12. Compounds according to claim 9, characterized in that R [deep] 3 is ethoxy and R [deep] 4 is oxo. 13. Compounds according to claim 9, characterized in that R [deep] 3 is butylamino and R [deep] 4 is oxo. 14. Compounds according to claim 9, characterized in that R [deep] 3 is methylamino and R [deep] 4 is oxo. 15. Compounds according to claim 9, characterized in that R [deep] 3 is methoxy and R [deep] 4 is oxo. 16. Compounds according to claim 9, characterized in that R [deep] 4 is methylimino and R [deep] 3 is methylamino. 17. Compounds according to claim 9, characterized in that R [deep] 4 is butylimino and R [deep] 3 is butylamino. 18. Compounds of the general formula II in the R [deep] 1 is lower-alkyl, phenyl or phenyl-lower-alkyl, R [deep] 2 is hydrogen, lower-alkyl or phenyl, R [deep] 7 is hydrogen, halogen or lower-alkoxy, R [deep] 8 hydrogen, or means, n is an integer with a value from 2 to 6 and R [deep] 11 and R [deep] 12 are identical or different and each represent a lower alkyl radical or, together with the nitrogen atom, a heterocyclic ring of the formulas or mean, where R [deep] 13 is hydrogen or lower-alkyl, and their salts with acids, in particular the pharmacologically acceptable salts. 19. Compounds according to claim 18, characterized in that R [deep] 1 alkyl with 1 to 4 carbon atoms, R [deep] 2 hydrogen, R [deep] 7 hydrogen, chlorine, bromine or alkoxy with 1 to 4 carbon atoms, R [ deep] 8 or means, n is an integer with a value from 2 to 4 and R [deep] 11 and R [deep] 12 are identical or different and represent methyl or ethyl. 20. Compounds according to claim 19, characterized in that R [deep] 1 ethyl, R [deep] 7 hydrogen, chlorine or methoxy and R [deep] 8 hydrogen, or means. 21. Compounds according to claim 20, characterized in that R [deep] 7 is chlorine and R [deep] 8 is hydrogen. 22. Compounds according to claim 20, characterized in that R [deep] 7 and R [deep] 8 are each hydrogen. 23. Compounds according to claim 20, characterized in that R [deep] 7 is chlorine and R [deep] 8 - (CH [deep] 2) [deep] 3-N (CH [deep] 3) [deep] 2 is. 24. Compounds according to claim 20, characterized in that R [deep] 7 is methoxy and R [deep] 8 - (CH [deep] 2) [deep] 3-N (CH [deep] 3) [deep] 2 is. 25. Compounds according to claim 20, characterized in that R [deep] 7 is hydrogen and R [deep] 8 - (CH [deep] 2) [deep] 3-N (CH [deep] 3) [deep] 2 is. 26. Compounds according to claim 20, characterized in that R [deep] 7 is chlorine and R [deep] 8 means. 27. Compounds according to claim 20, characterized in that R [deep] 7 is methoxy and R [deep] 8 means. 28. Compounds according to claim 19, characterized in that R [deep] 1 is ethyl, R [deep] 7 is n-butoxy and R [deep] 8 is hydrogen. 29. Compounds of the general formula III in the R [deep] 1 lower-alkyl, phenyl or phenyl-lower-alkyl, R [deep] 2 hydrogen, lower-alkyl or phenyl, R [deep] 9 hydrogen or lower alkoxy, R [deep] 10 hydrogen, or means, n is an integer with a value from 2 to 6, R [deep] 11 and R [deep] 12 are identical or different and each represent a lower alkyl radical or R [deep] 11 and R [deep] 12 together with the nitrogen atom form a heterocyclic ring of the formulas or mean, where R [deep] 13 is hydrogen or lower-alkyl, R [deep] 14 and R [deep] 15 are identical or different and each mean hydrogen or lower-alkyl, or R [deep] 14 and R [deep] 15 together with the nitrogen atom form a heterocyclic ring of the formulas or mean, where R [deep] 13 has the above meaning, as well as their salts with acids and in particular the pharmacologically acceptable salts. 30. Compounds according to claim 29, characterized in that R [deep] 1 alkyl with 1 to 4 carbon atoms, R [deep] 2 hydrogen, R [deep] 9 hydrogen or methoxy, R [deep] 10 or R [deep] 13 is hydrogen or methyl, n is an integer with a value from 2 to 4, R [deep] 16 is alkyl with 1 to 4 carbon atoms and R [deep] 11 and R [deep] 12 are identical or different are and are each methyl or ethyl. 31. Compounds according to claim 30, characterized in that R [deep] 1 ethyl, R [deep] 9 hydrogen, R [deep] 10 or and R [deep] 16 denotes alkyl having 1 to 4 carbon atoms. 32. Compounds according to claim 31, characterized in that R [deep] 10 means. 33. Compounds according to claim 31, characterized in that R [deep] 10 means. 34. Compounds according to claim 31, characterized in that R [deep] 10 means. 35. Compounds according to claim 31, characterized in that R [deep] 10 means. 36. Use of the compounds according to claims 1 to 35 as psychotropic and anti-inflammatory drugs.