HU190390B - Process for producing octahydro-pyrazolo-square bracket-3,4-g-square bracket closed-quinolines - Google Patents

Abstract

The title compds. of formula (XIII) were prepd. by reacting compds. of formula (XII) with pyridine hydrochloric acid salts and chromium trioxides. In the formulas, R is C1-3 alkyl, alkyl, or benzyl, and Z' is C1-2 alkyl or phenyl-substd. C1-2 alkyl. C1-3 alkyl includes n- propyl and iso-propyl, and C1-2 alkyl includes methyl and ethyl.

Description

(57) EXTRAS

The present invention relates to a process for the preparation of compounds of the formulas Ic and Id and their salts.

In the formulas

R is hydrogen, cyano or C1-3 alkyl, R 'is hydrogen, -COO- (Cl-C2) alkyl or -CH ₂ OH, with the proviso that when R is C 1-3 alkyl , R * is other than hydrogen.

-1190 390

This invention relates to octahydropyrazolo [3,4-g] quinolines of formula Ic and Id and their pharmaceutically acceptable salts.

The compounds Ic and Id can be used as intermediates in the preparation of octahydropyrazolo [3,4-g] quinolines of the formulas Ia and Ib having dopamine agonist activity.

The octahydropyrazolo [3,4-g] quinolines of the formulas Ia and Ib are compounds wherein

R is C 1-3 alkyl or allyl and R 'is hydrogen or -CH ₂ SCH ₃ .

The process comprises the preparation of a compound of formula VIIIa wherein

R 1 is hydrogen, cyano, C 1 -C 3 alkyl or allyl, and R ^{1 is} hydrogen or -C-O- (C 1-2).

is reacted with a hydrazine hydrate and then, when cyano R is reacted with zinc and acetic acid, and the resulting compound wherein R is hydrogen is reacted with an alkyl or allyl halide or reductive alkylation with a corresponding aldehyde and metal hydride ¹ is other than hydrogen, reacted with a metal hydride, the resulting intermediate in which R ¹ is -CH 2 OH is reacted with a nucleophilic reagent, and the resulting intermediate in which R ¹ is -COO- (C 1-2) - alkyl or -CH 2 OH is reacted with the sodium salt of methylmercaptan, and thus a Ia or Ib produced compounds of formula I wherein is a group of formula R ¹ -CH ₂ SCH _third

The novel intermediates of formulas Ic and Id which can be prepared by the process of the present invention are compounds of the formula wherein

R is hydrogen, cyano or C1-3 alkyl, and R ¹ is hydrogen, -COO (I-2 szénatomso) alkyl or -CH ₂ OH, with the proviso that when R is C 1-3 alkyl R ¹ is other than hydrogen.

According to the invention, the process is carried out by:

a) for the preparation of compounds of formulas Ic and Id wherein R is as defined above and R ^{1 is} hydrogen or - COO - (C 1 -C 2) -alkyl, a compound of formula VIII - wherein R is hydrogen and R ^{4 is} hydrogen; -COO- (C 1 -C 2) -alkyl, reacted with hydrazine hydrate, or

Compounds where R ¹ is -CH ₂ OH, Ic and Id representing COO- (Cl-C2) alkyl group, the compound is treated with a metal hydride is in R ^1, or b) a compound of formula Ic and Id

c) for the preparation of compounds of formulas Ic and Id wherein R ^{1 is} as defined above and R is hydrogen, the compounds Ic and Id of the cyano group in R are reacted with zinc and acetic acid and optionally converted to a free compound.

All salts of these intermediates may be used for purification or synthetic processes.

In the above formulas, the term "C 1 -C 2 alkyl" includes methyl and ethyl, and the term "C 1 -C 3 alkyl" even includes n-propyl and isopropyl.

Pharmaceutically acceptable acid addition salts of compounds of formula Ic-Id include inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, nitric, phosphoric and the like, as well as non-toxic salts derived from phenyl (substituted) alkanoic, hydroxyalkanoic and alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically acceptable salts include sulfate, pyrosulfate, hydrogen sulfate, sulfite, hydrogen sulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, -, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, capronate, heptanoate, propiolate, oxalate, malonate, succinate, subborate, sebacate, fumarate, maleate, , mandelate, butin-1,4-dioate, hexin-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate -, chlorobenzenesulfonate, xylene sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, maleinate, tartrate, methanesulfonate, propanesulfonate, naphthalene , naphthalene 2-sulfonate and the like.

The compounds of formula Ic are systematically named 4,4a, 5,6,7,8,8a, 9-octahydro-1H-pyrazolo [3,4-g] quinolines, and the compounds of formula Id are 4,4a, 5,6 , 7,8,8a, 9-octahydro-2H-pyrazolo [3,4-g] quinolines. These two structures represent a tautomeric pair and the tautomers represented by the structures are in dynamic equilibrium. In addition, the compounds of formulas Ic and Id wherein R ^{1 is} hydrogen have two chiral centers, at the ring attachment, at carbon 8a and 4a. Thus, the compounds may exist in the form of two racemates, commonly referred to as trans-d1-racemate and cis-d1-racemate.

The following examples illustrate the process of the invention.

Example A Preparation of trans-dl-5-cyano-4,4a, 5,6,7,8,8a, 9-octahydrolH (and 2H) -pyrazolo [3,4-g] clnoline g of 4-benzoyloxycyclohexanone, 38 ml of pyrrolidine, some crystals of p-toluenesulfonic acid monohydrate and 1000 ml of benzene are mixed. The reaction mixture was refluxed for one hour under nitrogen atmosphere in a Dean-Stark water separator. The reaction mixture was then cooled and the .190,390 volatile components were removed in a vacuum evaporator. The residue from the pyrrolidine-enamine formed by the reaction of 4-benzoyloxycyclohexanone was dissolved in 1000 ml of dioxane without further purification and 64 g of acrylamide were added. The reaction mixture was then refluxed under nitrogen for two days, then cooled and the volatiles removed by evaporation in vacuo. The reaction mixture was diluted with ethyl acetate, and the ethyl acetate layer was separated, washed with water, then with saturated aqueous sodium chloride. The ethyl acetate phase was dried and the volatiles removed by vacuum evaporation. The residue is 2-oxo-6-benzoyloxy-3,4,5,6,7,8-hexahydroquinoline and 2-oxo-6-benzoyloxy-3,4,4a, 5,6,7- A mixture of hexahydroquinoline formed during the reaction is dissolved in chloroform and the chloroform solution is chromatographed on florisil. Chloroform containing increasing amounts (0-2%) of ethanol was used as eluent. Those fractions shown by TLC to contain 2-oxo-6-benzoyloxy-3,4,5,6,7,8-hexahydro-quinoline and its Δ ⁸ * ⁸ ** isomer were combined and the solvent removed therefrom in vacuo . The residue was crystallized by trituration with hexane to give 6-benzoyloxy-3,4,5,6,7,8-hexahydro-1H-quinolin-2-one and the corresponding 3,4,4a, 5,6,7-hexahydro- a crystalline mixture of a derivative. The mixture was recrystallized from ether / hexane to melt at 130-150 ° C.

Analysis results:

Calculated: C 70.83%, H 6.32%, N 5.16%; Found: C, 71.05; H, 6.19; N, 5.33.

The NMR spectrum of the product isolated as described above showed that the mixture was about 60%

Contains 6-benzoyloxy-3,4,5,6,7,8-hexahydro-1H-quinolin-2-one and 40% 3,4,4a, 5,6,7-hexahydroisomer.

2-oxo-6-benzoyloxy-3,4,5,6,7,8-hexahydro-quinoline and Δ ⁸ * ^{8 'one} isomer prepared above for 4-benzoyloxy g of cyclohexanone were dissolved without further purification In a mixture of 300 ml of tetrahydrofuran and 300 ml of dimethylformamide. Sodium hydride (14 g) was added to give the quinoline sodium salt. After stirring for 20 minutes at room temperature under nitrogen, 55 g of benzyl bromide in 75 ml of tetrahydrofuran are added slowly over 10 minutes. The reaction mixture was stirred for an additional hour at 32-45 ° C and then diluted with water. The aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was separated, washed with water and saturated brine, and dried. By evaporation of ethyl acetate, 1-benzyl-2-oxo-6-benzoyloxy-3,4,5,6,7,8-hexahydroquinoline and 1-benzyl-2-χο6-benzoyloxy-3,4-4a A mixture of 5,6,7-hexahydroquinoline is obtained;

Yield: 106 g.

106 g of the above mixture are dissolved in 1 L of tetrahydrofuran and the solution is cooled in an ice water bath and 40 g of lithium aluminum hydride are added in portions. After the addition was complete, the reaction mixture was refluxed under nitrogen for about 4 hours. The mixture was cooled and the excess lithium aluminum hydride decomposed with ethyl acetate. Addition of 10% aqueous sodium hydroxide decomposes the organometallic compounds present in the mixture. The reaction mixture was then diluted with water. The resulting aqueous mixture was extracted several times with chloroform. The chloroform extracts were separated and combined. The combined extracts were washed with a saturated aqueous sodium chloride solution and dried. The residue obtained by evaporation of chloroform gave 1-benzyl-6-hydroxy-1,2,3,4,5,6,7,8-octahydroquinoline and 1-benzyl-o-hydroxy-1,2,3,4,4a, 5 , A mixture of 6,7-octahydroquinoline. (Both the 2-oxo and 6-benzoyloxy groups react with lithium aluminum hydride to form octahydroquinoline, which has a free alcohol group at C 6.) The resulting compound mixture is dissolved in ether and the ether solution is cooled and introducing gaseous anhydrous hydrochloric acid to prepare the hydrochloride of the quinoline isomers. The quinoline hydrochlorides are insoluble and are separated by decanting the ether. The residual salts were dissolved in a mixture of methanol (100 mL) and tetrahydrofuran (400 mL). The solution is cooled and 30 g of sodium cyanoborohydride are added in portions. After the addition was complete, the cooling bath was removed and the reaction mixture was stirred at room temperature for 1.25 hours and then poured into a mixture of aqueous hydrochloric acid and ice. The acidic solution is extracted with ether and the ether extract is discarded. The acidic solution was made alkaline with 10% aqueous sodium hydroxide solution and the basic mixture was extracted several times with chloroform-isopropanol. The organic extracts were combined, and the combined extracts were washed with saturated aqueous sodium chloride solution and dried. Evaporation of the solvent gave trans-dl-1-benzyl-6-hydroxydecahydroquinoline; yield 53.6 g. The overall yield of the six steps was 73% based on the recovered 4-benzoyloxycyclohexanone starting material.

Trans-dl-1-benzyl-6-hydroxydecahydroquinoline (g) was dissolved in dichloromethane (1.5 L) and cooled in an ice-water bath. Bromcian (50 g) was added and the reaction mixture was stirred for 15 hours at room temperature. The mixture was successively washed with n aqueous hydrochloric acid and water and dried. Evaporation of the solvent gave a residue containing trans-dl-1-cyano-6-hydroxydecahydroquinoline. This residue was dissolved in chloroform and the chloroform solution was chromatographed on 300 g of florisil, eluting with chloroform containing increasing amounts of methanol (0-2%). TLC indicated that the fractions containing the desired cyano compound were combined and the solvent removed by vacuum evaporation from the combined fractions. 22.5 g of trans-dl-1-cyano-6-hydroxydecahydroquinoline are obtained.

Trans-dl-1-cyano-6-hydroxy-decahydroquinoline (22.5 g) was dissolved in dichloromethane (1200 mL). Pyridine hydrochloride: chromium trioxide (Sarett's) (33 g) was added and the reaction mixture was stirred at room temperature under nitrogen for about 6 hours and then filtered. The filtrate was concentrated in vacuo and the concentrate was 300 g of flori3

-3190 390 silica chromatographed. Chloroform containing 1% methanol was used as eluent. The fractions which were found to contain trans-dl-1-cyano-6-oxo-decahydroquinoline by TLC were combined and the combined fractions evaporated to dryness in vacuo. The residue was recrystallized from ether / chloroform to give trans-dl-1-cyano-6-oxo-decahydroquinoline, m.p. 86-88 ° C; yield:

18.9 g.

Analysis results:

Found: C, 67.39%; H 7.92%, N 15.72%; Found: C, 67.15; H, 7.75; N, 15.46.

Trans-dl-1-cyano-6-oxo-decahydroquinoline (17.6 g) was dissolved in benzene (200 ml) to which dimethylformamide dimethylacetal (100 g) was added. The reaction mixture was refluxed under nitrogen for about 20 hours and then cooled. The solvent was evaporated in vacuo to give a residue containing trans-dl-1-cyano-6-oxo-7- (dimethylaminomethylene) decahydroquinoline. The compound was purified by chromatography on 300 g of florisil, eluting with chloroform containing increasing amounts of methanol (0-2%). There was thus obtained 10.2 g of transdl-1-cyano-6-oxo-7-dimethylaminomethylene-decahydroquinoline, m.p. 159-163 ° C. The product was recrystallized from toluene to give crystals, m.p. 162-164 ° C. Analysis results:

Calculated: C, 66.92; H, 8.21; N, 18.01; Found: C, 67.14; H, 8.16; N, 18.04.

Trans-dl-1-cyano-6-oxo-7-dimethylaminomethylene-decahydroquinoline (10.2 g) was dissolved in methanol (400 ml). 2.8 g of 85% hydrazine were added and the reaction mixture was stirred under nitrogen for about one day. The volatile ingredients are then removed by vacuum evaporation. The residue was dissolved in chloroform and the chloroform solution was chromatographed on 150 g of florisil. Chloroform containing increasing amounts of methanol (2-5%) was used as eluent. The fractions containing the desired octahydropyrazoloquinoline by TLC were combined and evaporated to dryness by evaporation of the solvent. Yield: 6.3 g. The residue was recrystallized from ethanol to give a mixture of trans-dl-5-cyano-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazolo [3,4-g] quinoline and 1H tautomer, m.p. 193-195 ° C.

Analysis results:

Calculated: C 65.32%, H 6.98%, N 27.70%; Found: C, 65.48; H, 6.80; N, 27.64.

Example B Preparation of trans-dl-4,4a, 5,6,7,8,8a, 9-octahydro-1H (and 2H) -pyrazolo [3,4-g] quinoline

860 mg of trans-dl-5-cyano-4,4a, 5,6,7,8,8a, 9-octahydro-1H and -2H-pyrazolo [3,4-g] quinoline (obtained in Example A), 5 g of zinc powder Water (10 ml) and acetic acid (50 ml). The mixture was refluxed for 18.5 hours under nitrogen, then filtered and the filtrate was poured onto ice. The resulting aqueous mixture was basified with 14N ammonium hydroxide solution and the resulting alkaline-aqueous phase was extracted several times with chloroform-isopropanol. The organic extracts were combined, and the combined extracts were washed with saturated brine and dried. The residue obtained by evaporation of the solvent contains trans-dl-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazolo [3,4-g] quinoline and the 1H tautomer. The residue was dissolved in ethanol and 0.70 ml of 12N aqueous hydrochloric acid was added. Dihydrochlorides of transdl-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazolo [3,4g] quinoline and 1 H tautomer

Mp 284-287 ° C; Yield: 780 mg. Analysis results:

Calculated: C, 48.04; H, 6.85; N, 16.80; Found: C, 48.07; H, 7.05; N, 16.83.

Example C trans-dl-5-n-Propyl-7-ethoxycarbonyl-4,4a-5,6,7 8,8a, 9-octahydro-1H (and

Preparation of 2H) -pyrazolo [3,4-g] quinoline A mixture of n-propylamine (ml) and toluene (400 ml) was cooled in an ice-water bath. Add dropwise

A solution of 16.5 g of ethyl α-bromomethyl acrylate in 50 ml of toluene was added and the mixture was stirred under cooling for about 25 minutes. A solution of 11 g of 4-benzoyloxycyclohexanone in 75 ml of toluene is then added dropwise. The resulting mixture was refluxed under nitrogen for about 23 hours. The reflux condenser is equipped with a Soxhlet 5A sieve to remove water. The reaction mixture was cooled and filtered. The filtrate was evaporated to give the residue n-propyl-3-ethoxycarbonyl-6-benzoyloxy-1,2,3,4,5,6,7,8-octahydroquinoline and 1-n-propyl-3-ethoxycarbonyl. A mixture of -6-benzoyloxyl, 2,3,4,4a, 5,6,7-octahydroquinoline. The residue was dissolved in a mixture of ether and chloroform and the resulting solution was saturated with hydrogen chloride gas while maintaining the temperature at 0-5 ° C. The solvent was then decanted from the crystalline hydrochloride salts formed and the salts dissolved in 100 mL of methanol. Tetrahydrofuran (300 mL) was added and the resulting solution was cooled in an ice water bath. 15 g of sodium cyanoborohydride are then added portionwise with stirring and cooling. After the addition was complete, the reaction mixture was stirred for an additional 1.25 hours and then diluted with aqueous sodium bicarbonate. The aqueous basic mixture was extracted several times with ethyl acetate. The ethyl acetate extracts were combined, and the combined extracts were washed with saturated aqueous sodium chloride solution and dried. Evaporation of the solvent affords trans-dll-n-propyl-3-ethoxycarbonyl-6-benzoyloxy-decahydroquinoline. This was dissolved in a mixture of 400 ml of methanol and 100 ml of 2N aqueous sodium hydroxide solution. The solution was stirred for 64 hours at room temperature under nitrogen and the volatiles removed by evaporation in vacuo. The residue was suspended in a mixture of 800 ml of ethanol and 15 ml of 12 N aqueous hydrochloric acid. The esterification mixture was heated to reflux and distilled

190,390 approximately 300 ml of solvent were removed. An additional 300 mL of methanol was added to the reaction mixture and refluxed for 26 hours in an apparatus equipped with a Soxhlet 3A sieve. The reaction mixture was cooled, diluted with aqueous sodium bicarbonate solution, and the basic mixture was extracted several times with chloroform. The chloroform extracts were combined, and the combined extracts were washed with a saturated aqueous sodium chloride solution and dried. Evaporation of the chloroform and chromatography on 150 g of florisil gives 10.3 g of the residue which is formed from the trans-dl-1-n-propyl-3-ethoxycarbonyl-6-hydroxydecahydroquinoline formed by the above hydrolysis. Chromatography was performed using chloroform containing increasing amounts of methanol (2-10%) as eluent.

A solution of 8.8 g of trans-dl-1-n-propyl-3-ethoxycarbonyl-6-hydroxydecahydroquinoline and 400 ml of methylene chloride is prepared. To this solution was added 4.1 g of sodium acetate followed by 10.8 g of pyridine hydrochloride: chromium trioxide reagent and the mixture was stirred for about 22 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The resulting concentrate was dissolved in chloroform and the chloroform solution was chromatographed on 150 g of florisil. Chloroform containing increasing amounts of methanol (1-2%) was used as eluent. The fractions containing TLC containing trans-dl-1-n-propyl-3-ethoxycarbonyl-6-oxo-decahydroquinoline were combined and the solvent was removed from the combined fractions. 3.48 g of the 6-oxo derivative are obtained as a residue. The 6-oxo derivative was dissolved in 100 mL of toluene to which 25 mL of dimethylformamide dimethylacetal was added. The resulting mixture was refluxed for 44 hours under nitrogen and allowed to stand at room temperature for a further 4 days. The volatiles were removed by vacuum evaporation and the residue consisting of trans-dl-1-n-propyl-3-ethoxycarbonyl-6-oxo-7- (dimethylaminomethylene) decahydroquinoline formed during the reaction was purified by chromatography. For chromatography, it is dissolved in chloroform and chromatographed on florisil using chloroform containing increasing amounts of methanol (2-5%) as eluent. The fractions containing the desired 7-dimethylaminomethylene compound were identified by TLC and the solvent was evaporated in vacuo.

IR (CHCl?)

1720 cm ^-1 ester> C = O 1540 cirr> N-C = C-CO

Nuclear Magnetic Resonance Spectrum (CDCl 3) (60 MHz) cps, triplet, N-CH ₂ CH ₂ C ₃ Cps, triplet, -O-CH ₂ CH ₃

246 cps, quartet, —O — CH ₂ CH ₃

186 cps, singlet, -N (CH ₃ ) ₂

448 cps, b. singlet,> C = C-H

A solution of trans-dl-1-n-propyl-3-ethoxycarbonyl-6-oxo-7-dimethylaminomethylene-decahydroquinoline (2.24 g) and ethanol (150 ml) was prepared. added

Hydrazine hydrate (0.45 mL) was added and the mixture was stirred at room temperature for about 17 hours. The reaction mixture was then concentrated in vacuo.

Trans-dl-5-n-propyl-7-ethoxycarbonyl-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazolo (3,4-g] quinoline and trans-dl-5 The residue containing a mixture of n-propyl-7-ethoxycarbonyl-4,4a _J 5,6,7,8,8a, 9-octahydro-1H-pyrazolo [3,4-g] quinoline was dissolved in chloroform and the resulting solution 35 g The fractions containing the desired pyrazoloquinoline by TLC were combined and the solvent was evaporated in vacuo. ethoxycarbonyl4,4a 5,6,7,8,8a, 9-octahydro-2H-pyrazolo [3,4-g] quinoline and 1H-tautomer thereof, m.p. 125-127 DEG C., 75% yield. :

Calculated: C 65.95%, H 8.65%. N, 14.42%; Found: C 65.75%, H 8.42%, N 14.16%.

Example D Trans-dl-5-η-Propyl-7-hydroxymethyl-4,4a, 5,6,7,8,8a, 9-octahydro-1H (and-2H) -pyrazolo [3,4- g] Quinoline Preparation of trans-dl-5-n-Propyl-7-ethoxycarbonyl-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazolo [3,4-g] quinoline dihydrochloride; the 1H tautomer mixture (3.7 mmol), prepared as described in Example C, was dissolved in 200 mL of tetrahydrofuran. Lithium aluminum hydride (1 g) was added portionwise. The reaction mixture was stirred at room temperature under nitrogen for about 16 hours and then cooled. Ethyl acetate and 10% aqueous sodium hydroxide solution were added to react with excess lithium aluminum hydride and decompose the organometallic compound present. The reaction mixture was then diluted with water and the aqueous mixture was extracted several times with a mixture of chloroform and isopropanol. The organic phases are separated and combined. The combined phases were washed with saturated aqueous sodium chloride solution and dried. By evaporation of the solvent, trans-dl-5-n-propyl-7-hydroxymethyl-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazolo [3,4-g] quinoline and 1H a mixture of its tautomer. The residue was dissolved in ethanol to which was added 0.2 ml of 12N aqueous hydrochloric acid. The residue obtained by evaporation of the volatile constituent is trans-dl-5-n-propyl-7-hydroxymethyl-4,4a, 5,6,7,8,8a, 9-octahydro-2H- and ΙΗ-pyrazolo [3, It consists of 4-glucinoline dihydrochlorides. The residue is dissolved in a mixture of methanol and acetone to give crystals which decompose 270-275 'Con. Yield: 350 mg.

The above reaction was repeated with 1.55 g of trans-dl-5-n-propyl-7-ethoxycarbonyl-4,4a, 5,6,7,8,8a, 9-octahydro-2H-pyrazole [3, 4-g] quinoline is reduced with excess lithium aluminum hydride in tetrahydrofuran. The reaction product, trans-dl-5-n-propyl-7-hydroxymethyl-4,4a, 5,6,7,8,8a, 9-octahydro-1 H- and 2 H -pyrazolo [3,4-g] quinoline from a mixture of chloroform and ethanol

-5190 390 crystallized. Melting point of crystalline product

Claims (5)

167-169 'C. Found: C, 67.43; H, 9.30; N, 16.85; Found: C, 67.21; H, 9.13; N, 16.62. c) for the preparation of compounds of formulas le and Id wherein R1 is hydrogen and R are hydrogen, reacting compounds Ic and Id of the cyano group in R with zinc and acetic acid and optionally converting the resulting free compound to a salt. 1 page drawing -6190 390 NGO ₄ : C 07 D 471/04 H R1 N2 A process for the preparation of compounds of the formulas Ic and Id and their salts, wherein: R is hydrogen, cyano or C1-3 alkyl, R 'is hydrogen, -COO- (TOMOS 1-2C) alkyl or -CH ₂ OH, with the proviso that when R 1-3 szénato- 5 represents ^one mos alkyl, R ¹ is other than hydrogen -, wherein a) Ic and Id compounds of formula wherein R is as defined above and ^R1 is hydrogen or COO (1-2C) alkyl, ²⁰ a compound of formula VIII - wherein R is as defined above and R ^{4 is} hydrogen or -COO- (C 1 -C 2) alkyl- hydrazine hydrate, or preparing b) a compound of formula Ic and Id, Ic and Id where representative -COO- (C1-2) -alkyl represents R ¹ CH ₂ OH, R * report compound is treated with a metal hydride, or Process a) according to claim 1, trans-dl-5n-propyl-7-ethoxycarbonyl-4,4a, 5,6,7,8,8a, 9-octahide ¹⁰ ro-1H (and -2H) for the preparation of pyrazolo [3,4-g] quinoline tautomers, wherein the starting material is trans-dl-1-n-propyl-3-ethoxycarbonyl-6-oxo-7-dimethylaminomethylene-decahydroquinoline. Process a) according to claim 1, which is trans-dl-5n-propyl-7-hydroxymethyl-4,4a, 5,6,7,8,8a, 9-octahydro-1 H - (and -2 H) - for the preparation of pyrazolo [3,4-g] quinoline tautomers, characterized in that trans-dl-5-n-propyl-7-ethoxycarbonyl-4,4a, 5,6,7,8,8a, 9-octahydro- A mixture of 2H-pyrazolo [3,4g] quinoline dihydrochloride and the 1H tautomer of the dihydrochloride salt is reacted. Process a) according to claim 1, which is trans-dl-5-cyano-4,4a, 5,6,7,8,8a, 9-octahydro-1 H - (and -2 H) pyrazolo [3,4-g]. quinoline tautomers, wherein the starting material is trans-dll-cyano-6-oxo-7-dimethylaminomethylene-decahydroquinoline. Claims 5 6 | R1 ^ So ^ -ía'N '(la) ζ ^Ν Γ H-N2 ¹ » R (Ib) R1 R1 HN VKi • Ν '