DE1670634A1 - Process for the preparation of 2-aminoalkyl- (pyrrol-3-yl) -ketones - Google Patents

Description

P 1 ^ -70 634.6 '16. JUL11Ü70

Endo Laboratories Inc.

Garden City, NY, V.St. Am.

Process for the preparation of 2-aminoalkyl- (pyrrol-3-yl) -ketones

The primary aim of the invention is to provide Improvements in the synthesis of 2-aminoalkyl- (pyrrol-3-yl) '- ketones of formula A

0R _X

Il I ⁵ /

C GH-CHp Nv

γ Α.

in the R-, a hydrogen atom, lower alkyl with at most β carbon atoms, phenyl, phenylalkyX with up to 3 carbon atoms im Alkyl radical, substituted phenyl or phenylalkyl with substituents on the phenyl ring in the form of halogen, ■ alkyl with at most 4 carbon atoms, alkoxy with a maximum of 4 carbon atoms or halogenated alkyl with a maximum of 4 carbon atoms or 2-, 3- or 4-pyridyl,

R _? , IU and R ₂ , alkyl, alkenyl or cycloalkyl with a maximum of 8 carbon atoms, phenyl, halophenyl, lower alkoxyphenyl, thienyl, furyl or benzyl and

- ² υηίθί läQ6n lAru / «ι nue. J. ιίγ. i build 3 ciae AndeKungas «* · v · 4.9.

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Rp- a hydrogen atom, alkyl, alkenyl or cycloalkyl with mean a maximum of 8 carbon atoms, phenyl or benzyl, where

R and R ^ form an alicyclic ring with the highest 8 carbon atoms can be connected

R ₂ and R can be connected to form an alicyclic ring with a maximum of 8 carbon atoms, in the case of the formation of an S-aminomethyl - ^^ jöjY-tetrahydro - ^ - oxoindole this by a 6- or 7-carbon atom of the Lower alkyl radical hanging in the indole nucleus,

R, and Rj- form an alicyclic ring with a maximum of 8 carbon atoms can be connected, and

X and Y as being identical or different from one another are a hydrogen atom, Lower alkyl, lower alkynyl, lower alkynyl, cycloalkyl, Hydroxy-lower alkyl, alkoxy-lower alkyl, dialkoxy-lower- ^ alkyl, dialkylamino, (dialkylamino) alkyl, lower acyloxyalkyl, carbamyloxy lower alkyl, phenyl lower alkyl, iieterocyclo or Heterocyclo-lower alkyl or can be linked to form a heterocyclic ring of at most 8 members.

Such heterocyclic rings formed from X and Y can for example aziridinyl, lower alkyl azidinyl, piperidino, lower alkyl piperidino, di (lower alkyl) piperidino, lower alkoxypiperidino, Hydroxypiperidino, lower alkyl carbonyl .; pheny! piperidino, hydro: spnenyl-piperidino, low acyloxypiperidino, Pyrrolidinyl, lower alkyl pyrrolidinyl, lower alkoxypyrrolidinyl, Hydroxypyrrolidinyl, morpholino * lower alkyl Imorpholino, di (lower alkyl) morpholino, thiomorpholine, Lower alkyl thiomorpholino, di (lower alkyl) thiomorpholino ,. Lower alkoxy thiomorpholino, piperazinyl, lower alkyl

20981 kl 15 90

piperazinyl, di (lower alkyl) piperazinyl, lower alkoxyplperazinyl, Phenylpiperazinyl, dilorphenylpiperazinyl, Tolylpiperazinyl, methoxyphenylpiperazinyl, hydroxyalkylpiperazinyl, Lower acyloxy-lower-alkyl-piperazinyl, carbamyloxy-lower-alkyl-piperazinyl, Hexamethylimino, tetrahydroisoquinolyl, azafjiraalkyl or azabicycloalkyl, with below "Lower alkyl" and "lower alkoxy" are understood to mean both straight-chain and branched radicals having a maximum of 5 carbon atoms will.

These formal Α-compounds have pharmacodynamic effectiveness, i.e. act on the central nervous system and are particularly suitable as sedatives and antidepressants.

Some of the simpler 5- (secondary amino) methyl compounds Formula A has already been obtained with the help of the Mannieh reaction of a pyrrol-3-yl-ketone with formaldehyde or a formaldehyde-yielding one Compound, e.g., paraformaldehyde, and an X-NH-Y base according to Reaction Scheme I given below. These can be quaternized and treated with Base as starting materials for the process according to the invention be used.

As a result of resonance between the electron-rich pyrrole ring and the ketone carbonyl in the pyrrole ketones, these molecules are less reactive than structurally related aromatic ones Ketones, e.g. pheny! Ketones or naphthy! Ketones. One episode This inertia consists in the fact that the Mannich reaction with many important X-NH-Y bases or their corresponding Salting is going on very slowly. Experience has shown that the long reflux times required for the complete Conversion is required, side reactions occur, and often dark-colored, difficult-to-clean products are formed.

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Of the various Mannich reactions carried out, those with dimethylamine hydrochloride are the fastest and give better yields and purer products. ^

According to the invention, it has now been found that pure formula Α products can be used as starting material in high yield advantageously formula B compounds according to the structural representation below which are easily prepared from quaternized salts of the dimethylamine Mannich bases of the formula A. can by splitting off the tertiary amine residue from them under alkaline conditions.

Characteristic of the process according to the invention is that Follow the aforementioned steps as shown in Reaction Scheme II below.

The dimethylamine Mannich base is made with an alkyl halide or sulfate quaternized and the resulting quaternary salt treated with aqueous alkali, the stable methylene derivative forms, which upon further reaction with a new base provides a high-quality end product in high yield.

The success of the inventive method is based on unusual stability of the methylene compounds of the formula B (in which, by the way, the symbols R to R ^ have the same meaning as in formula A) by opposing polynier-forming Side reactions are much more stable than structurally comparable aryl derivatives, such as the Acrylopheiione.

Many primary and secondary amines are stored at room temperature in solvents such as lower alcohols, lower ketones or lower esters, voluntarily and with evolution of heat of Formula B compounds. But you can instead

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which the addition reactions perform well at temperatures between 50 ° and 150 ° C in boiling under reflux solvents, wheref up to 150 ⁰ C, the heating preferably takes place in pressure vessels ^ IRRI case 'of low boiling solvents and temperatures.

Occasionally, it is convenient to use excess base as a solvent.

Depending on the nature of the reactants, the reaction time varies between 1 minute and 24 hours. Most of the reactions but are completely expired in less than 8 hours.

Even if prostitute thylamine-Manniohbas en the cheapest starting material represent, one can instead use other lower alkylamino Mannich bases and monocyclic saturated ones heterocyclic bases, e.g. the piperidino-Mannich base, ver. turn around.

Although it is advantageous to remove the methylene compounds by means of aqueous, inorganic alkali, e.g. dilute caustic soda, to develop; but you can also use aqueous ammonia for this or use strong organic bases, e.g. triethylamine.

The synthesis can also be carried out with one step less, using the same starting materials but not actually isolating the methylene compound and the new organic base at the same time as alkali source and conversion partner used. This modified embodiment is also explained in the later reaction scheme II, where is worked with 2 moles of organic base.

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If you work with longer conversion times, an equilibrium is established so that you only get a single mole of must use new organic base per mole of quaternized Mannich base, as by driving off the volatile amine, so -according to the scheme- of the trimethylamine, complete implementation 'is achieved.

Because they are generally easy to manufacture, ~ it is true that the trimethylammonium salts are best for carrying out the invention; but experience has shown that s for the production of the formula B-methylene compound also use other quarry salts of the formula C given below. In this Formula C mean

, R ,, R ₁ ^ and R are the same radicals as in formula A, RT, R ₇ and Ro lower alkyl with a maximum of 4 carbon atoms, where Rg and R _{7 are connected} to form a ring with a maximum of 7 carbon atoms! can be, and ' ν

Z an inorganic ion such as halide or methosulfate.

The reaction is suitable for the preparation of a number of substituted β- (amino, mono- and disubstituted-amino) alkyl (pyrrol-5-yl) ketones according to formula A. Such compounds are, for example, pyrrole compounds according to formula A, 4,5,6 , Y-tetrahydro - ^ - oxo-indoles according to formula D and 4,5 »6» 7-tetrahydro-4-oxoisoindoles according to formula E. The important common structural grouping is highlighted in formulas A, D and E by a dashed border. All compounds with this common structural grouping have similar, valuable, pharmacodynamic activity. They act on the central nervous system and are suitable as sedatives, analgesics and antidepressants.

For me. 1 A

j 8 h / ^x :

Formula B.

2 1

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Formula C

C - CH-CH Ν—

B.

Rea] Ktion5echenia_I C-CH ₂ + CH ₂ O + NH ^. HCl

R ₄

ίί ρ, χ

C-CH-CHjrfC .HCl

Reaction ^ scheme II '

It

C-CH- CH ₀ - N. ^J + CH, Br 2 Nn ₁₃ . 3

Ri

Il

CH ₃

.-C-CH-CH «N-S-CH V · Br

1-R ₂ R5

NaOH formula B

(one or two moles) ^N Y

Form »l A

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Formula D

Formula E.

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- ία -

The following examples are intended to further the invention explain. All temperature data contained in them mean Centigradeβ

example 1

2 _J ⁱ t- _J 5-trimethylpyrrol-3-yl-2- (4-phenylpiperazinyl) ethyl ketone

A suspension of 16.2 g (0.1 mole) 2,4,5-trimethylpyrrol-3-yl vinyl ketone in 30 ml of ethyl acetate was mixed with 16.2 g of N-phenylpiperazine mixed. The mixture warmed up, became clear and then crystals of the product deposited, which after recrystallization melted from toluene at 122 to 133 °.

The 2,4,5-trimethylpyrr-ol-3-yl-vinyl ketone used here as starting material was made in the following way:

A mixture of 15.1 g (0.10 mol) of methyl 2,4,5-trimethylpyrrol-3-yl-ketone was boiled, 12.3 g (0.15 mol) dimethylamine hydrochloride and 4.5 g (0.15 mol) dimethylamine hydrochloride and 4.5 g (0.15 mol) of paraformaldehyde in 250 ml of anhydrous ethanol under reflux conditions, gave more after 24 hours 1.5 g of paraformaldehyde added, the reflux continued for a further 24 hours, then the solution was evaporated in the Vacuum on a steam bath to dryness and the solid residue crystallized with the addition of charcoal a total of three times from ethanol. The 2- (dimethylamino) ethyl-2,4,5-trimethylpyrrol-3-yl-ketone hydrochloride obtained in this way melted at up to 198.5 °. One freed from it through treatment with unmarried people aqueous ammonia the base, took it up in acetone and treated it with methyl bromide, whereby the quaternary salt quickly parted and after recrystallization from methanol melted at 188-190 °. -

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The methobromide was dissolved in water and made with excess Treated 2N sodium hydroxide solution, the yellow vinyl compound deposited in crystals and precipitated after unicrystallization Ethanol melted at 147 to 148.5 °.

By treating the 2,4,5-trimethylpyrrol-: 5-yl-vinyl ketone with suitable bases the following compounds were obtained?

2,4, ^ -trimethylpyrrole - ^ - yl-piperidinoethyl-ketone hydrochloride, P. 184 to 185 °;

2,4,5-trimethylpyrrol-3-yl-morpholinoethyl-ketone, F, 103 bis 105 ° and 2- (4-ethoxycarbonyl-4-phenylpiperidino) ethyl-2,4,5-trimethylpyrrol-3-yl-ketone, 104 to 106 ° F.

Example 2

4-butyl-2,5-dimethylpyrrol-; 5-yol-pyrrolidinoethyl-ketone

When adding 10 g of 4-butyl-2,5-dimethylpyrrol-3-ylvinyl-ketone, 15 ml of pyrrolidine and 15 ml of ethanol occurred self-heating to 50 °, and a clear solution formed, which was briefly on the steam bath to complete the reaction heated and then evaporated to leave a solidifying residue. He delivered after recrystallization the desired product from cyclohexane, mp 96 ° to 97 °.

The 4-butyl-2,5-dimethylpyrrol-3-yl vinyl ketone used here as starting material was made in the following way:

2-Qximino-3-heptanone and 2,4-pentanedione were synthesized by Knorr to 4-butyl-2,5-dimethylpyrrol-3-yl-methyl ketone, M.p. 124 to 125 °, condensed. A mixture of 0.1 mol of this ketone, 0.15 mol of diethylamine hydrochloride and 0.15 ×

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$ 2 0 9 U / 1 690

Moles of paraformaldehyde in 250 ml of ethanol under reflux conditions, added another 1.5 g of paraformaldehyde after 24 hours, continued refluxing for an additional 24 hours and The solution then evaporated to dryness, whereby 4-butyl-2,5-dimethylpyrroleK ^ -yl ^ -dimethyl.aminoethyl-ketone hydrochloride, P. 157 to 160 °. This salt became like in Example 1, the base is released, which by treatment with methyl bromide 4-butyl-2,5-dimethylpyrrol-3-yl-1- (dimethylamino) ethyl ketone methobromide, P. 166 to 168.5 °. This methobromide was dissolved in water and treated with aqueous sodium hydroxide solution as in Example 1, the vinyl ketone precipitated, which after recrystallization from isopropanol at lo6 ° melted.

By treating the 4-butyl-2,5-dimethylpyrrol-j5-yl-vinyl ~ ketones with suitable bases gave the following compounds:

4-butyl-2,5-dimethylpyrrol-j5-yl-2,6-dimethylmorpholinoäthy 1-ketone, P. 94 to 95 °;

4-butyl-2,5-dimethylpyrrol-3-yl-hexamethyleneiminoethyl-ketone hydrochloride dihydrate, P. l4o to l4l ° j 4-butyl-2,5-dimethylpyrrol-3-yl-2- (4-pyridylmethylamino) ethyl ketone, F. I27 to 128 ° and

4-Butyl-2,5-dimethylpyrrol-3-yl-2- (5-pyridylmethylamino) ethyl ketone dihydroxy chloride, pp. ^{189 to I.9I 0.}

In a manner analogous to Examples 1 and 2, 4-fithy 1-2,5-dimethylpyrrol-3-yl-vinyl ketone, M.p. 148 to 149 °, prepared by treating with suitable bases as follows Connections provided:

2- (Benzylamino) ethyl-4-ethyl-2, S-diinethylpyrrole - ^ - yl-ketone, M.p. 112 °;

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2- (ethylamino) ethyl-4-ethyl-2, S-

F. 8ο to 84 °; . "'.. ·

4-ethyl-2, S-dimethylpyrrol - ^ - yl ^ (methylaraino) ethyl ketone, F, 83 to 84 ° and

2-aminoethyl-4-ethyl-2,5-dimethylpyrrol-: 5-yl-ketone.

In a similar way, 2,5-Dlmethyl-4-propylpyrrol-; 5-yl-vinyl ketone, F. "I06 to 107.5 °, and continued it with selected Bases to the following compounds around:

2,5-dimethyl-4-propylpyrrol ~ 3-ylHiiorpholinoäthyl-ketone, F. 107 to 108.5 ° j

2- (4-methylpiperazinyl) ethyl-2,5-dimethyl-4-propylpyrrol-3-yl ketone, F. 97 to 99.5 ° and

2- (l, 2,3,4-tetrahydro-2-isoGhinolinyl) ethyl-2,5-dimethyl-4-propylpyrrol-3-yl-ketone, F. II5 to 116 °.

Example ^

4,5,6,7-tetrahydro-2,3-dimethyl-5-methylene-4-oxoindole was heated, 10 ml of morpholine and 50 ml of anhydrous ethanol for 8 hours under reflux conditions, the solution evaporated in a vacuum to dryness, the residue was taken in. In hydrochloric acid on, filtered, made the solution as in Example 1 with aqueous Ammonia was alkaline, the resulting precipitate was filtered off, washed with water and the product crystallized from toluene to, F. I65. up to 168 °.

The 4,5,6,7-tetrahydro-2,5-dimethyl-5-methylene-4-oxoindole used here as starting material was made in two ways:

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1st way: I63 g (1 mol) of 4,5,6,7-tetrahydro-2,3-dimethyl-4-oxoindole, 81.5 g (1.0 mol) of dimethylamine hydrochloride and 45 g (1.5 Mol) paraformaldehyde in 2500 ml of ethanol for a total of 48 hours under reflux conditions, after 8 and after 24 hours a further 10 g of paraformaldehyde were added, then 1200 ml of ethanol evaporated and the remaining mixture cooled, 4,5,6 , 7-Tetrahydro-2,3-dimethyl-5 ~ (dimethylamine) methyl-4-oxoindole hydrochloride crystallized out, which after recrystallization from ethanol melted at 230 °.

fe From the salt, as in the earlier examples with aqueous Ammonia released the base, of which 51 g in 350 ml Isopropanol have been dissolved. Methyl bromide in gaseous form was introduced into the solution, with heating to about 45 ° entered and after a few minutes the methobromide crystallized out started. The methyl bromide addition was 40 minutes continued until the precipitation stopped increasing. After standing for several hours at room temperature, the crystals were filtered off, washed with isopropanol and dried (yield 70 g) and recrystallized from a mixture of anhydrous methanol and ethanol, whereupon they melted at 222 °.

10 g of this methobromide were in a mixture of 50 ml * Dissolve ethanol and 50 ml of water and add 20 ml of n-sodium hydroxide solution added, whereupon the methylene compound was deposited as a yellow pest substance, which after filtering off, washing with Water and recrystallization melted at I97 to I98,

2nd way: 16.3 g (0.10 mol) of 4,5,6,7-tetrahydro-2,3-dimethyl-4-oxoindole, 10.7 g (0.10 mol) of piperidine hydrochloride and 4, 5 g (0.15 mol) of paraformaldehyde in 250 ml of ethanol under reflux conditions, gave a further 1 g of para

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formaldehyde, continued the reflux for up to a total of 48 hours, then evaporated the solution in vacuo on a steam bath, took up the residue in 150 ml of water, to which 10 ml of 2N hydrochloric acid were added, freed the resulting solution from insoluble, residue consisting of unreacted starting material by filtration, made the filtrate alkaline with ammonia water, as in earlier examples, filtered off the precipitated white solid substance, washed it with water, dried it at 80 ° and crystallized it several times from benzene and then from benzene. Heptane around. This gave 4,5 * 6,7-tetrahydro-2, ^ - dimethyl ^ -oxo ^ -piperidinomethyl-indole, mp 179 °, which was converted into the methoiodide salt in acetone with excess methyl iodide, which crystallized on standing overnight , F. 219 to 220 °. As in the first way, this salt was converted into the methylene compound, mp 197-198 ⁰ , by treatment with alkali. By refluxing 4,5,6,7-tetrahydro-2,3-dimethyl-5-methylene-4-oxoindole and propargylamine in ethanol, 4,5,6,7-tetrahydro-2,3-d! Methyl- 4-oxo-5- ^ T2-propynylamino) methyl_ _< 7i ⁿ ^ ^o l as' hydrochloride, m.p. 220 °. ..

Similarly · was obtained by treating with the appropriate Bases the following compounds:

4.5 _J 6,7-tetrahydro-2,3-dimethyl-5- (2-methyl-1-aziridinyl) methyl-4-oxoindole, m.p. to 121 °;

4,5 * β, 7-tetrahydro-2,3-dimethyl-4-oxo-5-thiomorpholinomethy1-indole, F. 200 to 201.5 °)

2,3-dimethyl-4-oxolndole hydrochloride, mp 215 °; 4,5,6,7-tetrahydro-2,5-methyl-4-OXo-5- (4-phenyl-1-piperazinyl) methylindole, m.p. 215-216 ° j

5- ^ "(J-Azabicycloi ^ .2.2) non-5-yl) methy17-4,5,6,7-tetrahydro-2,3-dimethyl-4-oxoindole, M.p. 215 to 217 °;

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2 0 9 8 U / 1 5 9 0

^ t 5 ί 6,7-tetrahydro-2 ₃ 3-dimethyl-5- (2,6-dimethylmorpholino) methyl-4-oxoindole, m.p. 166 to 168 °.

Similarly, one obtained;

^{4,5,6i7-tetrahydro-2-methyl-5-di} methylaminomethyl-4-oxo-3-phenylindole, mp 182-183 °, is converted with methyl bromide in the quaternary salt, this finally by alkali treatment in the methylene compound and the latter by heating with morpholine in ethanol to give 4,5,6,7-tetrahydro-2-methyl-5-morpholinomethyl-4-oxo-3-phenylindole, and

Fe 2-butyl-4,5,6,7-tetrahydro-3-methyl-5- ( ⁽ 3.imet; hylamino) methyl-4-oxoindole, mp 138.5 to 139.5 °, converted it with methyl bromide into the quaternary salt, this by alkali treatment into the methylene compound and the latter finally by heating with thiemorpholine in ethanol to give 2-butyl-4 _s 5,6,7-tetrahydro-3-methyl-4-oxo-5-thiamorpholinomethyl-indole.

Example 4

j-Ethyl-4,5,6-7-tetrahydro-2-methyl-4-oxo-5-piperidinomethyl- indole hydrochloride

14.1 g (0.08 mol) of 3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole, 9.8 g (0.12 mol) of dimethylamine hydrochloride W and 3.6 were boiled g (0.12 mol) of B. arafprmaldehyde in 200 ml of ethanol for 40 hours under reflux conditions, the solution evaporated to dryness in vacuo, the residue digested with a mixture of 150 ml of water and 10 ml of 2N hydrochloric acid, filtered unreacted , insoluble starting material and, as above, added the acidic solution drop by drop with ammonia water while stirring. The amine which crystallized out was purified by dissolving it in 1N hydrochloric acid, reprecipitating it with ammonia water and recrystallizing it three times from benzene

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and thus obtained the base, P. 170 to 175 °.

From it, mannitol methyl bromide in acetone produced the methobromide salt, P. 215 to 21.8 °, and from this finally set the "3-ethyl- ^, 5 * 6,7-tetrahydro-2-methyl-5" by treatment with 2N sodium hydroxide solution -methylene-4-oxoindole, P. 217-218 ° freely. When cooked, these methylene compound with piperidine in ethanol for 8 hours under reflux conditions, formed a new Mannich base, namely the corresponding Piperidinomethylverbindung, P. I65 to I67 ⁰ whose Hydrochlorld salt melted at I90 to I92 ^{0. '}

The above 5-methylene compound gave when treated with appropriate Bases the following other compounds, some of which were produced pure as salt:

3-ethyl-4,5,6,7-tetrahydro-5- (2-methoxyethylamino) methyl-2-methyl-4-oxoindole, 108-109 °;

5- (2-sthoxyethylamino) methyl-3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole, 101-102 °;

3-Sthyl-5- (ethylamino) methyl-4,5,6,7-t6trahydro-2-methyl-4-oxoindole, P. 150 to 151 °; ■ '

5-Ethyl- ⁱ l-, 5,6,7-tetrahydro-2-methyl-5- (5-morpholino-propyl- K amino) methyl -. ^ - oxoindole-dihydrobromide, P. 15 ² I- ⁰ (Dec.);

3-Ethyl- ¹ l-, 5,6,7-tetrahydro-5- (2-hydroxy-1-methylethylamino) methyl-1-methyl-1-oxoindole, P. 172 ° i

5-ethyl-4,5,6,7-t.et r ahydro-5 - (2-hydroxy ethylamino) methy 1-2 methyl-4-oxoindole, F. 16I to I63 ⁰ j

3-A * ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxo-5 - ^ "(4-pyridylmethylamino) methyl | 7indole, F. 209 to 214 ° j

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methyl7indole, P.-IS5 to 187 ⁰ ;

3-rthyl - 4.5.6 _t 7-tet.rahydro-2-methyl-5- (2,2-dimethylhydrazine) methyl-4-oxoindole hydrobroniid, P. 202 to 203.5 °;

(rf <-methylphenäthylaniino) methyl7indol hydrochloride, F. I86 to I89 ^0;

3-Ethyl-4,5 _J 6,7-tetrahydro-2-raethyl-4-oxo-5- ^ ~ (3-piperidylmethylamino) methyl7indol, F. 142-144 °;

5- / ~ (3-diraetbylamino) propylarairio7methyl - 3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole hydrobromide, P. 165 to 166 °;

5- _< / "(2- (dimethylamino) ethyl) amino7methyl-3-ethyl-4,5,6,7-tetrahydro-2-raethyl-4-oxoindole hydrobromide, P. 168 to 169.5 °;

3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxo-5 - / "(di-2-propynylamino) raethyl7indole, M.p. 143 to 145 °;

3-ethyl-4,5,6,7-tetrahydro-5- (methallylamino) methyl-2-methyl-4-oxoindole, P. 113 °;

3-Sthyl-4,5,6,7-tetrahydro-5 - ^ "(2-tetrahydropyranyl-methyl) amino7rnethyl-.2-methyl-4-oxoindole, P. 135 to I36 ^0;

3-Sthyl-5 - ^ "(2,2-hexamethyleneimino) amino7methyl _4,5,6-f 7-tetrahydro-2-raethyl-4-oxoindole hydrobromide isopropoxide, F. 89 or 90 °;

3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxo-5- _< / "(1H-tetrazol-5-yamino) methyl7indole, mp 234 °;

5-allylaminomethyl-3-ethyl-4,5,6,7-tetrahydro-2-met l ^ l-4-οχο-indole, M.p. 130 to 131.5 °;

3-ethyl-4,5, β, 7-tetrahydro-2-raethy 1-4-OXO-5- / "(2-propynylamino) methyl O ^ indole hydrochloride, P. 204 to 204.5 °;

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4-oxoindole, mp 155-156 °;

5- _j / ~ (2,2-diethoxyethyl) amino7methyl-3-ethyl-4,5,6 _i 7-tetrahydro-2-methyl-4-oxoindole, P. 95 to 96 ° ;

3-fitIiyl-4,5,6,7-tetrahydro-2-methyl-5- (morpholinoamino) methyl-4-oxoindole, F. 157 to °

5- (Dlbutylaraino) methyl-3-ethyl-4 _i 5 _i 6,7-tetrahydro-2-methyl-4-oxoindole, m.p. 98 to 100 ° j

3-ethyl-4,5,6,7-tetrahydro-2-raethyl-5 - (4-met] iylpiperidino) methyl-4-oxoindole> F. 167 to I69 ^0; >

3-Sthyl _J-4 5,6,7-tetrahydro-2-raethyl-4-oxo-5 - / ^"(Jl -P ^r opylpiperid" - ino) methyl7indol, F. I6I to 162.5 ° ϊ

5- (4-Benzylpiperidino) raethyl-3-ethyl-4,5,6,7-tetrahydro-2-fflethyl-4-oxoindole'phydrochloride, F. 1δ2 ° ί

5- (4 "Carbamoylpiperidino) methyl-3-ethyl-4,5,6 _J, 7-tetrahydro-2-methyl-4-oxoindole, F. 210 to 212 °;

5- ^ ^'1' is benzyl (2-propynyl) amino7raethyl-3-ethyl-4 ₃ 5,6,7-tetrahydro] iydro-2-methyl-4-oxoindole-hydiOchlorid, F. 197-198 ⁰ J

3-Ethy1-4,5 * 6,7-tetrahydro-5- (p-methoxybenzylaraino) methyl-2-raethyl-4-oxoindole hydrochloride, 123 to 125 °;

3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxo-5- _< / ~ (2,2-diphenylethylamino) methyl7indole, mp 136-138 °;

5- (9-Acridinylaraino) methyl-3-ethyl-4,5,6,7-tetrahydro-2 ^ methyl-4-oxoindole, M.p. 223 to 226 °;

3-ethyl-4,5,6,7-tetrahydro-2-methyl-5- ^ ~ methyl (2-propynylamino7methyl-4-oxoindole _i F, 130 to 130.5 °;

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3-ethyl-4 ₎ 5> 6,7-tetrahydro-5- (hexamethyleneimino) methyl-2-methyl-4-oxoindole, mp 168 to 169.5 °; ■

5-Kthyl 4,5,6-7 _{J-tetrahydro-2-methyl-5-} (methylphenäthylamino) methyl-4-oxoiridol hydrochloride, F. I87 to I89 ^0;

3-ethyl-5- (furfurylmethylamino) methyl-4,5 ₃ 6,7-tetrahydro-2-methyl-4-oxoindole, mp 103-104 °;

3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxo-5-i _</ "4- (3-phenylpropyl) piperidino7raethyl} indole hydrochloride, mp 174 to I76 ^0;

3-ethyl-4,5,6,7-tetrahydro-2-methyl-5-morpholinomethyl-4-oxoindole hydrochloride, 192.5 to 193 °;

5- (Benzylmethylamino) methyl-3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole, F. I30 to 132 ° j

5-butylaminomethyl-3-ethyl-4,5 _J, 6,7-tetrahydro-2-methyl-4-oxoindole, F. 131 ° i

5- (4-ethoxycarbonyl-4-phenylpiperidino) methyl-3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole, 188-189.5 °;

5- (l-Adamantanaminomethyl) -3-ätnyl-4,5,6,7-tetrahydro-2-methyl-4-dxoindol, F. I7I ^0; J

5- (3-Azabicyclo ^ "'3,2,27non-3-yl) methyl-3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole, F. 221 to 223 ° i

3-Ä "ethyl-5- (2-ethyl-1-aziridinyl) methyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole citrate, M.p. 145 to 150 ° (dec.);

3-fithyl-4,5,6,7-tetrahydro-2-methyl-4-oxo-5-pyrrolidinylmethylindol, F. I70 to I72 ^0;

3-fitnyl-4 _^ 5 "6 * 7-tetrahydro-2-methyl-4-oxo-5-thiomorpholinomethylindol, F. 175 to I76 ^0;

- 21 -

2098U / 1590

3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-.oxo-5- ( ¹ ^ -phenyl-lpiperazinyl) methylindole hydrochloride, mp 190-192 ° j

5- ( ² l-Benzyl-l-piperazinyl) methyl-3-ethyl-4,5,6,7p-tetralihydro-2-methyl-4-oxoindole, mp 186-188 ° ;

3-ethyl-4,5, β, 7-tetrahydro-2-methyl-5- (4-methyl-l-plperazinyl) methyl-4-oxoindole, m.p. 148 to 149 °;

hydro-2-methyl-4-oxoindole, E..221 to 223 °;

^{3-Kthyl-4,5,6,7-tetr>} ahydro-2-methyl-5- (2,6-dimethylmorpholino) methyl-4-oxoindole, F. I6O ° j

Example 5

ⁱ <-j5y ^ j7 "'retrahydro-2-methyl-4-oxo-5- (4-phenylpiperazinyl) methyl l' ^ -propylindole

The procedure according to Example 3 was followed by reaction of 4,5,6,7-tetrahydro-2-methyl-4-oxo-3-propylindole with dimethylamine hydrochloride and paraformaldehyde and subsequent basic treatment 5- (dimethylamino) methyl-4,5,6,7-tetrahydro-2-methyl-4-oxor3-propylindole and converted with methyl bromide into its methobromide salt, mp 221 to 222 °. This Salt provided the appropriate solution when treated with 2N sodium hydroxide solution Methylene compound, m.p. 179 to 1810, and this finally the above by reaction with H-phenylhydrazine End product, mp 169-171 °.

Reacted with propargylamine, the same methylene compound gives 4,5,6,7-tetrahydro-2-methyl-4-oxo-3-propyl-5- _< / "(2-propynylamino) methyl / indole hydrochloride, F. 175 up to 179 °

- 22 -

2098U / 1590

Example 6

4,5 _J 6,7-tetrahydro-1,3-dimethyl-4-oxo-5- / ~ (4-phenylpiperazinyl) methyl-isoindole

6.0 g of 4,5,6,7-tetrahydro-1,3-dimethyl-5-methylene-4-oxo-isoindole were boiled, 6.0 g of N-phenylpiperazine and 50 ml of ethanol 20 The ethanol evaporated for hours under reflux conditions from and diluted with ether, whereupon the product crystallized out, which after recrystallization from methanol at 184 to 185.5 ° melted.

Serving as the starting material methyl compound set forth obtained as follows: was treated with 2,5-Dimethylpyrröl succinic anhydride and boron trifluoride etherate in benzene, reduced the resulting 2,5-dimethyl-y-oxopyrryl-3-butyric acid, mp 154 to I56 ^0, wherein I90 ⁰ with hydrazine and alcoholic potassium hydroxide solution to give 2,5-dimethyl-3-pyrrole-3-butyric acid, this reduced acid cyclized directly with polyphosphoric acid to 4,5,6,7-tetrahydro-1,3-dimethyl-4-oxoisoindole without intermediate purification , M.p. 150.5 to 151.5 °, this compound boiled with dimethylamine hydrochloride and paraformaldehyde in ethanol under reflux conditions, dissolved the resulting 4,5,6,7-tetrahydrol, 3-dimethyl-5- (dimethylamine) methyl-4- oxoisoindole hydrochloride, mp 188 to 189.5 °, in water and put on from it by treatment with aqueous sodium hydroxide solution, the base, F. I69 to I7O ⁰ freely. It was dissolved in acetone and to 2j58 ° converted with methyl bromide in the Methobromidsalz, F. 236, which gave, after addition of aqueous sodium hydroxide solution to its aqueous solution- a yellow methylene compound which melted after recrystallization from alcohol at I50 to I5I ^0th

4,5,6,7-tetrahydro-1,3-dimethyl-5-methylene-4-oxoisoindole settles in a similar manner with morpholine to 4,5,6,7-tetrahydrol, 3-dimethyl-5-morpholinomethylr4-oxoisoindole, F. 148 to 149 °

- 23 2098U / 1590

- 23- 1 ^ 70634

(as hydrochloride F. 172 to ΐγ4 °) and with cyclohexylamine 5-Cyclohexylaminomethyl-4 * 5,6,7-t-ethrahydro-1,3-dimethyl-4-oxoisoindole, P. 127 to 128 ° to.

Example 7 "-

oxoisoindole hydrochloride

A mixture of 5 * 5 g of 4,5 * 6,7-tetrahydro-1,2,3-trimethyl-5-methylene-4-oxoisoindole was boiled and 25 ml of morpholine for 24 hours under reflux conditions, the excess evaporated Morpholine and diluted the residue with water, which solidified and, after recrystallization from cyclohexane-benzene, melted at 97 to 98.5 °. The product was converted to its hydrochloride salt, mp 213-214 °.

The methylene compound used as the starting material was prepared as follows: 1,2,5-Trimethylpyrrole was treated with succinic anhydride and boron trifluoride etherate in benzene, the resulting 4- (1,2,5-trimethylr-3-pyrryl) -4-oxobutyric acid, F. 162.5 to 163.5 °, at 190 ⁰ with hydrazine hydrate and potassium hydroxide to form 4- (1,2,5-trimethyl-3-pyrryl) butyric acid, this reduced acid cyclized directly with polyphosphoric acid to 4,5,6 without intermediate purification, 7-Tetrahydro-1,2,3-trimethyl-4-oxoisoindole, m.p. 82 to 83 °, boiling this compound with dimethylamine hydrochloride and paraformaldehyde in ethanol under reflux conditions, dissolved the resulting ¹ ^ * 5 »6,7-tetrahydro-1 , 2,3-trimethyl-5-dimethyl laminomethyl 1-4-oxoisoindole hydrochloride, mp 195 to 196 ⁰ , in water and released the oily base from it by treatment with aqueous sodium hydroxide solution. It was dissolved in acetone and converted with methyl bromide into the methobromide salt, melting point 197 to 200 °, which after treatment with aqueous sodium hydroxide solution gave the yellow methylene compound, melting point 103 to 1θ4 °.

- 24 -

209 814/1 S90

Example 8

4.5 _< 6.7 »tetrahydro-2,?, 6 ~ trimethyl« 5 »morpholinomethyl-4-oxoindole hydrochloride

Following the procedure according to Example .4 4,5,6,7-tetrahydro-2,3 _i 6-trimethyl-5-methylene-4-oxoindole, P. 205 ° after recrystallization from isopropanol, was prepared in such a way that starting from 4,5,6,7-tetrahydro-2, j5,6-trimethyl-4-oxoindole, mp 205.5 °, this compound in 5- (dimethylamine) methyl-4,5,6,7-tetrahydro -2,3,6-trimethyl-4-oxoindole, m.p. 152 to 155 ° and therefrom the methylene compound 'via the corresponding methobromide, P. 237 to 239 °, produced. Reacting this methylene compound with morpholine, piperidine or cyclopropylamine gave

4,5,6,7-tetrahydro-2,3,6-trimethyl-5-morpholinomethyl-4-oxoindole hydrochloride -1 / 2C ₂ Hf-OH, m.p. 18l to 182 ° after recrystallization from ethanol-acetone,

¹ ^ » 5 * β, 7-tetrahydro-2, 3,6-trimethy l-4-oxo-5-piperidinomethy 1-indole, mp 165 to 166 ° after recrystallization from toluene,

5- (Cyclopropylamino) methyl-4,5,6,7-tetrahydro-2,3,6-trimethyl-4-oxoindole hydrochloride. 1/2 GgH ₅ OH, F. 198 ⁰ (decomp.) After recrystallization from Ä 'ethanol-acetone.

Example 9

2,4,5-trimethylpyrrol-3-yl-2- (phenylplperazinyl) ethyl ketone

17.5 g (0.05 mol) of 2- (dimethylamino) ethyl-2,4,5-trimethylpyrrol-3-yl-ketone methoiodide were boiled, M.p. 206-207 °, and 8.1 g (0.05 mol) of N-phenylpiperazine in 400 ml of anhydrous Ethanol under reflux conditions, with the methoiodide dissolved and trimethylamine escaped in Qasform. After 1 hour the solution was poured onto a mixture of 300 g of ice and 50 ml

- 25 -

2098U / 1590.

Ammonia water, the product separating out with solidification. After recrystallizing from toluene, it melted at 132 to 133 ° and was found to be compatible with the product of Example 1 identical.

Example 10

4,5,6,7-tetrahydro-2,3-dimethyl-4-oxo-5- / ~ (4-phenylpiperazinyl) methyl / indole - ~ "~ -"

A mixture of 6.9 g obtained according to Example 3 was heated

rnethojodid, 2.85 g of N-phenylpiperazine and 300 ml of ethanol as long under reflux conditions until a clear solution resulted was. After concentration to 40 ml and storage in the refrigerator, this gave the product in crystal form, which, after recrystallization from ethanol, melted at 215 to 216 °.

Example 11

3-ethyl-4,5,6,7-tetrahydro-5- (4-hydroxy-4-pheny! Piperidino) -methyl-1-methyl-4- oxoindole

16.45 g (0.05 mol) of 5- (dimethylamine) methyl-3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole methobromide were boiled, 8.9 g (0.05 mol) of 4-phenyl-4-piperidinol and 150 ml of ethanol for 2 hours on a steam bath under reflux conditions, with methobromide dissolving over 10 minutes, and trimethylamine was released, the solution evaporated to 50 ml and poured it into excess ammonia water, the precipitating solid amine was filtered off, washed with water, dried and recrystallized twice from dioxane and then from benzene, F, I85 to 186 °.

- 26 -

209814/1590

Example 12

According to Example 3, 1,2,3,4,5,6,7,8-Octahyd.ro-4-oxocarbazole were prepared with dimethylamine hydrochloride and paraformaldehyde 1,2,3,4,5,6,7,8-C) ctahydro-3- (dimethylamine) methyl-4-oxocarbazole, F. 172 to 173.5 ° ago, this base dissolved in acetone and soon converted into it with methyl bromide methobromide salt crystallizing out of the solution, P. 217 bis 219 ° (decomp.), Um. This salt was in 30% aqueous Dissolved methanol and poured it into the pale yellow with ln sodium hydroxide solution l * 2j3,4,5,6,7 »8-octahydro-3-methylene-4-oxocarbazole converted, which said goodbye and after recrystallization from ethanol melted at 219 to 220 °,

Example 13

2- (dimethylamino) ethyl-4 _{<5.6 J} 7-tetrahydro-2-methylindole-3-yl ketone isopropoxide-hydroohlorid

10.5 g 4,5,6,7-tetrahydro-2-methylindol-3-yl-methyl ketone (prepared according to the instructions of Treibs & Dinelli, Ann. Chem. 517 (1935), 152-59), 7.5 g of dimethylamine hydrochloride and 3 g. Paraformaldehyde for 20 hours under a nitrogen blanket "reflux boiled in 150 ml of ethanol. The resulting solution was evaporated in vacuo, the residue was taken up in dilute hydrochloric acid, the solution was filtered, made alkaline with ammonia, kept in the refrigerator overnight and ■ m from a semi-solid amine decanted. The latter was redissolved in dilute hydrochloric acid, filtered and precipitated again with ammonia. The semi-solid mass obtained in this way showed the fuzzy P. 105 to 109 ° after drying. It was dissolved in isopropanol and then added to the Hydrochlorld converted, which after recrystallization from 2 s 1-isopropanol ether formed a solid which crystallized with 1 mol of isopropanol, P, 73 to 75 °.

- 27 -

2098U / 159Q

Example 14

5- (Cyclopropylamino) methyl "5» 6,7 / 8-tetrahydro-2 _> 3 ~ dimethyl- ' cyclohepta (b) pyrrole «-4 (1H) -one hydrochloride

In a similar way to the example. 8 was 5,6,7,8-5! Etrahydro 2,3-dimethyl-5-raethylene cyclohepta (b) pyrrol-4 (1H) -one, P. 162 to 163.5 ° after recrystallization from 50 $ aqueous alcohol; synthesized in such a way that one of 5,6,7,8-tetrahydro-2,3-dimethylcycloheptä (b) pyrrole-4 (lH) -one, mp 177 to I78 ⁰ ran out, in this connection 5- (dimethylamino ) rnethyl-5,6,7 »8-tetrahydro-2,3-dimethylcyclohepta (b) pyrrole-4 (lH) -one, F. II7 to II8 ⁰ * after recrystallization from benzene-cyclohexane, and converted from the methylene compound via produced the corresponding methobremide (indefinite F). Reacting this methylene compound with cyclopropylamine or morpholine gave

5- (Cyclopropylamino) methyl-5 _J 6,7,8-tetrahydro-2,3-dimethylcyclohepta (b) pyrrole-4 (1H) -one hydrochloride, melting point 18I to 182 ° after recrystallization from anhydrous isopropanol, and

5,6,7,8-tetrahydro-2,37methy1-5-morpholinomethylcyclohepta (b) pyrrol-4 (1H) -one, m.p. 147 to 1 ^ 7.5 °.

Example I5 *

4 (2H) -one

Following the procedure according to Example 4, 5,6-dihydro-1,3-dimethylcyclopenta (c) pyrrol-4 (2H) -one, melting point 244 to 2.k6 ° +. after recrystallization from toluene, prepared and converted into the Mannich base 5p- (dimethylamino) methyl-5 * 6-dihydro-1,3-dimethylcyclopenta (o) pyrrole-4 (2H) -onj | r, in the form of its I ^ rdrochloridsal- · Zes isolates this from excess after recrystallization

- 28 20-98 U / 1 69 0

Much anhydrous ethanol melted at 230 to 231 ° (decomp.). This salt was converted into the corresponding methobromide. delt, that in raw form according to the working method according to the example 11 was reacted with piperidine or morpholine. One received

.so

5,6-Dihydro-3., 3-dimethy 1-5-piperidinomethylcy clopenta (c) pyrrol-4 (2H) -one _J F. 151 to 152 ° after recrystallization from benzene-hexane, and. .

5,6-dihydro-1,3-dimethyl-5-morpholinomethylcyclopenta (c) fe pyrrol-4 (2H) -one, melting point 145 to 148 ° after recrystallization Benzene hexane.

Example 16

5- (dimethylamino) methyl-5,6 _J 7,8-tetrahydro-l, 3 ~ -one ditnethylcyclohepta (c) pyrrole-4 (2H)

Following the procedure of Example 4 was 5,6,7,8-tetrahydro-l, 3-dimethylcyclohepta (c) pyrrole-4 (2H) -one _i F. 136-137 ° after recrystallization from benzene-hexane, in 5- (Dimethylamino) methyl-5,6,7,8-tetrahydro-1-, 3-dimethylcyclohepta (c) pyrrol-4 (2H) -one, F, 128 to I3I ⁰ after recrystallization from benzene-hexane.

209 8 H /. 1590

Claims (1)

P a t e η t a ns ρ r ü c h e 1. Process for the preparation of 2-aminoalkyl- (pyrrol-3-yl) ketones of the formula A 0 R ₅ "* ■■ - ■ χ Il J / • C - CH CH NL ft ■ κ ¹ in which R ^ is a hydrogen atom, lower alkyl with a maximum of β carbon atoms, phenyl, phenyl-alkyl with up to 3 carbon atoms in the alkyl radical, substituted phenyl or phenyl-alkyl with substituents on the phenyl ring in the form of halogen, alkyl with a maximum of K. carbon atoms, alkoxy having at most k carbon atoms or halogenated alkyl having at most k carbon atoms or 2-, J5 ¹ or 4-pyridyl, Rp, R, and R ^ alkyl, alkenyl or cycloalkyl with at most 8 ^ carbon atoms, phenyl, halophenyl, lower alkoxyphenyl, Thienyl, furyl or benzyl and .v «.» AT " ⁵ °" Unterlaeen 1ΑΛ7 | 1 AU2 Nr.l 8att3d-Ä «l« UB ^ ^fl ·· «· ⁴ ·« ' ¹ «" 2098U / 1B90 Rp. A hydrogen atom, alkyl, alkenyl or cycloalkyl with a maximum of 8 carbon atoms, phenyl or benzyl, where R, and EL an alicyclic ring with a maximum of 8 carbon atoms can be connected R ₂ and R, - can be connected to an alicyclic ring with at most Ö carbon atoms, in the case of the formation of ι a 5-aminomethyl-4,5,6,7-tetrahydro-4-oxoindole this by a 6- or 7 carbon atoms of the lower alkyl pendant hanging from the indole nucleus may be substituted, R., and Rf. To an alicyclic ring with a maximum of 8 carbon atoms can be connected, and X and Y each, identically or differently, are each a hydrogen atom,. Lower alkyl, lower alkenyl, lower alkynyl, Cycloalkyl, hydroxy-lower alkyl, alkoxy-lower alkyl, Dialkoxy-lower alkyl, dialkylamino, dialkylamino-low alkyl, lower acyloxyalkyl, carbamyloxy lower alkyl, Phenyl-lower alkyl, heterocyclo or heterocyclo-lower denote alkyl or can be linked to form a heterocyclic ring of at most 8 members, characterized in that an optionally in Alkenyl-pyrrol-3-yol-ketone produced in situ Formula B. 0 " ^: ■ ■ .. Λ ^R ■ . 2 5 ^R l - 31 - 209814/1590 - 3- · in which R ,, R _p , R ₇ ,, H ₁ . and R ₁ - have the same meaning as in formula A, with a base of the formula X-NH-Y converts, in which X and Y also have the same meaning as in formula A. 2. The method according to claim 1, characterized in that the heterocyclic ring of aziridinyl, lower alkylaziridinyl, piperi- dino, lower alkylpiperidino, di (lower alkyl) piperidino, ™ lower alkoxypiperidino, hydroxypiperidino, (lower alkoxy) carbonyl-phenylpiperidino, hydroxy-phenyl-piperidino, lower acyloxypiperidino, pyrrolidinyl, lower alkylpyrrolidino, lower alkylpyrrolidino, lower alkylpyrrolidino, lower alkylpyrrolidino-alkyl, lower-alkylmorphol (lower-alkylpyrrolidino), lower-alkoxypyrrolidino-alkyl, lower-alkoxypyrrolidino-alkyl, lower-alkoxypyrrolidino-alkyl, lower-alkoxypyrrolidino-alkyl, lower-alkylpyrrolidino-alkyl, lower-alkoxypyrrolidino-oil, lower-alkoxy-pyrrolidino-alkyl, lower-alkoxypiperidino, hydroxypiperidino, hydroxypiperidino, lower-alkoxy) Niedrigalky! thiomorpholines, di (nieörigalkyl) thiomorpholino, Niedrigalkoxythiomorpholino, piperazinyl, Niedrigalkylpiperazinyl, Dt (lower alkyl) piperazinyl, Niedrigalkoxypiperazinyl, phenylpiperazinyl, Chlorphenyli ^ -perazinyl, Tolylpiperazinyl, Methoxyphenylpiperazinyl, hydroxyalkylpiperazinyl, Niedrigaeyloxy-niedrigalkylpiperazinyl, Garbamyloxy-niedrigalkylpiperazinyl, etc. hexamethyleneimino; Tetrahydroisoehinolinyl, Azaspiroalkyl or Azabicycloalkyl, where "lower alkyl" and "lower alkoxy" have not more than 5 carbon atoms. 3. The method according to claim 1, characterized in that R ^, Rn, and R _{c are} not connected to one another. 4. The method according to claim l _ä, characterized in that and Rc are connected to each other. - 32 - 2098H / 169Ö 52 - 5. The method according to claim 1, characterized in that R, and Rr. Are connected to each other, 3 5 6. The method according to claim 1, characterized in that IU and .R ₂ are connected to one another. 7 «Method according to claim 1, characterized in that R ₀ and R _c as well as R and R ,, are connected to one another. 2 5 3 4 8. The method according to claim 1, characterized in that the formula Α compound is formed in situ- by reacting the base with a compound of formula C reacted, in which R ₁ , R ₂ , R ,, R ^ and R_ have the same meaning as in claim 1 and Rg, R and Rg lower alkyl with not more than 4, C atoms, where Rg and R, ^ to one Ring of not more than 7 carbon atoms can be linked, and Z is an inorganic anion. 9β Method according to one of the preceding claims 1 to 8, characterized in that the formed formula A compound from ^ -Butyl - ^^ - dimethylpyrpoX - ^ - yl-pyrrolidinoethylketone, j5-, ethyl- »4,5,6,7-tetrahydro-2-methyl-4- - 33 20 9 8 U / 159 0 - οχο-5-piperidinomethylindole, 3-ethyl-4,5 * 6,7-tetrahydro-2-raethyl-5-niorpholinoraethyl-4-oxoindole _j , 4,5,6,7-tetrahydrol, 3-dimethyl- 5-morpholinomethyl-4-oxoindole, 4,5,6,7-tetrahydro- _{1,2 J} 3-triraethyl-5-worpholinometbyl- ⁱ l - oxoisoindole or 1,2,3 * 4,5,6,7, 8-Octaltydro: ~ 4-oxo-3-piperidinomethylcarbazole consists. 10. Compounds of the general formula ^Η ι in the ' R ₁ , R 1 and R ₂ , a hydrogen atom, alkyl with a maximum of β carbon atoms, phenyl, phenylalkyl with up to 3 carbon atoms in the alkyl radical, substituted on the ring by halogen, alkyl, haloalkyl or alkoxy with a maximum of 4 carbon atoms each Phenyl or phenylalkyl η 1,2 or 3, as an integer or zero. X and Y are identical or different from each other and are each a hydrogen atom, lower alkyl, lower alkenyl, lower alkynyl, Cycloalkyl, hydroxy-lower alkyl, alkoxy-lower - 34 -209814 / IBtO _ 34 - 1 r / 0634 alkyl, dialkoxy-lower alkyl, dialkylamino, dialkylanino-lower alkyl, Lower acyloxyalkyl, carbamyloxy lower alkyl, Phenyl-lower alkyl, heterocyclo or heterocyclo-lower alkyl mean or can be connected to form a heterocyclic ring of at most 8 members, as well as their pharmaceutically acceptable salts. 11. The compound of claim 10, wherein the heterocyclic moiety from aziridinyl, (lower alkyl) aziridinyl, piperidino, Lower alkylpiperidino, di (lower alkyl) piperidino, (lower alkoxy) piperidino, hydroxypiperidino, (lower igaoyloxy) piperidino, Pyrrolidinyl, - (lower alkyl) pyrrolidinyl, (Lower alkoxy) pyrrolidinyl, hydroxypyrrolidinyl, Morpholino ,, (lower alkyl) morpholino, thiomorpholines (Lower alkyl) thiomorpholino, di (lower alkyl) thiomorpholino, (Lower alkoxy) thiomorpholino, piperazinyl, (lower alkyl) piperazinyl, Di (lower alkyl) piperazinyl, (lower rigalkoxy) piperazinyl, phenylpiperazinyl, chlorophenyl perazinyl, Tolylpiperazinyl, methoxyphenylpiperazinyl, Iftrdroxyalkylpiperazinyl, lower acyloxy-lower alkylpiperazinyl, Carbamyloxy-lower alkylpiperazinyl, azabi <^ cycloalkyl, azaspiroalkyl, hexamethyleneimino or tetrahydroisoquinolyl, the terms "lower igaoyl", "Lower alkyl" and "lower alkoxy" are straight or mean branched chain groups with a maximum of 6 carbon atoms. - 35 - 209814/1590 12. 5- (Diinethylamino) methyl-4,5 »6,7-tetrahydro _-1J) 3-dimethyl-4-oxo-olndol. ■ 13. 5- (D
trimethyl-4-oxoisoindole. 14. 4,5,6,7-Tetr'ahydro-1 _i 3-dlmethyl-4-oxo-5- (piperidinomethyl) isoindole. 15 x 4 _i 5,6,7-tetrahydro-1,3-dimethyl-5-tnor-pholinomethyl-4- oxoindole. 16. 4.5 s 6 < _{.7 = tetrahydro-1 S} 2 _s 3-tr imethyl-5-morpho-thiolinomethyl-4-oxoindole. · 17. 5- (dimethylamino) methy1-5,6-dihydro-1,3-dimethylcyclopenta / "c7pyrrole-4 (2H) -pn. - 18. 5,6-Dihydro-1,3-aimethyl-5 "(morpfeualinomethyl) cyclopenta / c7pyrrol-4 (2H) -one. 19. 5- (Dimethylamino) methyl ~ 5 _{i i} 6,7 8-tetrahydro-.lj, 3-dimethylcyclohepta ^ "c7pyrrol ° 4 (2H) -one. 20. 5- (Cyclopropylamino) raethyl ~ 3 »= ethyl-4.5 _s .6,7-tetrahydro-2-methylene 1-4-QXoindole. 21. 5- (Cyclopropylamino) methyl-4,5,6,7- »tetr ^> ahydro-2,3 ₅ 6-trimetny1-4-oxoindole» 22. 3-] Ithyl-4-, 5,6 _i 7-tetrahydro »2-methyl-4-oxo-5- · ^" (2-propynylamino) methyl7indole. 23. 3-Ethyl-4,5,6,7-tetrahydro-2-methyl-5 - ^ "methyl (2-propynyl) arnino7Riethyl-4-oxoindole. 09814/1590 24. 5- (Ethoxycarbonyl-4-phenylpiperidino) methyl-3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindolo 25. 5- (Dimethylamino) methyl-5,6,7 * 8-tetrahydro-2,3-dimethylcyclohepta ^ "b7pyrTol-4- (2H) -one. 26. 2- (Sthylamino) ethyl-4-ethyl ~ 2,5-diraethylpyrrol-3-yl ketone. 27. 4-Butyl-2,5-diraethylpyrrol-3-yl-2- (4-pyridylmethylamino) ethyl ketone. . 28. 4-Butyl-2,5-dimethyl-pyrrol-3-yl-hexalnethyleniminoethylketone. 209814/1590