DE2302671A1 - 5-ACYL PYRROLE, THE METHOD OF MANUFACTURING IT AND ITS USE IN MEDICINAL PRODUCTS - Google Patents

Description

Camp Hill Road, Port Washington, Pennsylvania, Y.St.A.

"5-Acylpyrroles, process for their preparation and their use in pharmaceuticals "

Priority: January 21, 1972, V.St.A., ITr. 219 861 and 219 864

The invention relates to new 5-acylpyrroles of the general formula I.

i I

-CH-R-

in the R ₁ . the benzyl, cyclopantyl or cyclohexy group and R denotes a hydrogen atom or a lower alkyl radical, R ^ and R ₂ ? which are identical or different, represent hydrogen atoms or meth: / l groups and R- denotes the group -COOH, -COO- ( _{lower alkyl)% -0OiIH 0} or -CN, with the proviso that R is a lower alkyl radical . when R _{2 represents} a methyl group

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ORIGINAL INSPECTED

means R, the group -COOH or -COO-C-lower-alkyl), if R is a methyl group, and R and R_ are hydrogen atoms and R represents the group -COOH, -COO-C-lower-alkyl) or -CIT means when R ^. the Benzy! group is.

In the preferred 5-acylpyrroles of the general formula I denotes R, the group -COOH and they have the general formula 3

I-a '■ -. ■ -

CH-COOH

in which η has the value 1 or 2 and R, R ^ and R _{2 have} the meaning given above. Among these compounds, the compounds of the general formula Ia in which η is 2, that is to say the 5-cyclohexanoylpyrroles, are particularly preferred.

The other pyrroles of the general formula I, namely the esters, amides and nitriles, have the general formula I-b

(CH ₂ W j} p-, f2

in which n, R, R ^, and Rp have the above meanings and Z represents the group -COO-C-lower-alkyl), -GOMH ₂ or -CE . These compounds are also new and they are valuable intermediates for the preparation of the compounds of the general formula Ia. Particularly preferred compounds are the 5-cyclchoxa noyl derivatives.

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The term lower alkyl means unbranched or branched Alkyl radicals with 1 to 5 carbon atoms, such as the methyl, Ethyl, propyl, isopropyl, butyl, sec-butyl and pentyl groups.

The compounds of the general formula I in which R _{2 is} the cyclopentyl or cyclohexyl group, R _{2 is} a hydrogen atom and R _{5 is} the group -COO-C-lower-alkyl) are generally obtained from the corresponding cycloalkanoy by Friedel-Crafts synthesis Halide of the general formula II given below, preferably the cyclohexanoyl chloride or cyclopentanoyl chloride, · and a pyrrole-2-acetic acid ester of the general formula III given below, in which R ¹ denotes the group -COO- (lower-alkyl), in the presence of a Lewis acid , preferably a metal halide such as aluminum chloride or tin tetrachloride.

The nitrile compounds of the general formula IV given below, that is to say the compounds in which R ¹ denotes the nitrile group, R. denotes the benzyl, cyclopentyl or cyclohexyl group and R. and R ₅ denote hydrogen atoms, are prepared in a similar manner from a corresponding pyrrole compound of the general formula III produced.

The Friedel-Crafts synthesis is preferably carried out in a solvent, such as methylene chloride, 1,2-dichloroethane, carbon fiber or ifitrobenzene.

The acid derivatives obtained of the general below

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ORiGfNAL INSPECTED

my formula IV or IV ¹ can be saponified to the corresponding free carboxylic acids in a manner known per se, for example by heating in aqueous methanol with an alkali metal hydroxide. The alkali metal salt of the acid is formed, from which the free acid is set free by acidification. If the radical R ^ is the benzyl group, the acids can be converted into the corresponding lower alkyl esters in a manner known per se by reaction with the corresponding lower aliphatic alcohol.

The reactions described above can be represented by the following reaction scheme:

C-Cl

(II)

J-CH-B!

Friedel Crafts ..

(III)

(CHo

Lj

GH — R '

(IV)

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NaOH

HCl χ L /

-CH-COOH 2

-CH ₂ -CO Cl

Friedel- _CH ₂ -CN Crafts>

(in)'

^σ 6 ^Η 5

-CH ₂ -CO ^ _Ν

(IV) ¹

HIGH

lower r.

C ₆ H ₅ -CH ₂ -CO- ^ pJ R

Alkyl)

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For the preparation of the nitriles and esters of the general formula IV, in which R is a lower alkyl radical and Rp is the methyl group, becomes a derivative of the unsubstituted in the ei general / formula V obtained by Friedel-Crafts synthesis according to the above Eeaktionsschema described are prepared can, in a manner known per se, C-methylated, for example with a methyl halide, preferably the jclide,

in the presence of a strong base such as sodium amide or sodium hydride. It becomes the corresponding oc-methylnitrile and esters obtained according to the following reaction scheme:

Pl

¹ - ^Y (n
(V)

N "

. _,,. Base I /

(lower-alkyl) (lower-alkyl)

The corresponding free acids can be obtained in a manner known per se by hydrolysis.

The acetonitriles of the general formula I, in which R ^ the cyclopentyl or cyclohexyl group, R ^ a hydrogen atom, R a lower alkyl radical and R denotes the methyl group, v / ground likewise in a manner known per se by N-alkylation of a corresponding N-unsubstituted 5-G37cloalkanoylpyrrole-2-acetonitrile of the general formula VI and subsequent C-methylation of the 5-cycloalkanoyl-N-lower-alkyl-pyrrole-2-acetonitrile obtained with the corresponding lower alkyl halide bsw. Methyhalide as an alkali metal compound according to the following reaction scheme produced v / earth:

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^(CH | ^ c ₍

JL

cH ₂ -CN ν-

(lower alkyl)

CO-

CH

^ »J JL-CK-CN (lower alkyl)

After the N-alkylation or C-alkylation, the corresponding free acids are produced in a manner known per se by hydrolysis.

The amides of the general formula I, in which R ^ denotes the cyclopentyl or cyclohexyl group and R denotes the group -COMi ₂ , can be prepared in a manner known per se by partial hydrolysis of the corresponding ITitriles (R, = CN). The conversion of the nitriles into the amides is carried out, for example, by refluxing with sodium hydroxide solution for a relatively short time in order to stop the hydrolysis at the amide stage and not to bring about complete hydrolysis to the carboxyl group. The amides of the general formula I, in which R ^ denotes the cyclopentyl or cyclohexyl group, can also be prepared in a manner known per se by ammonolysis of the corresponding lower alkyl esters (R 1 = -COO-lower-alkyl). The amides obtained can be saponified in a manner known per se to give the corresponding free carboxylic acids (R .. = COOH).

The free carboxylic acids of the general formula I (R, = COOH)

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have anti-inflammatory activity. This is shown in the rat. paw test for edema set with kaolin, which in doze of about 5 to about 250 "mg / kg body weight can be suppressed. For example, with 5-cyclohexanoyl-1-methylpyrrole-2-acetic acid, a preferred compound of the invention, a 67pi "percent suppression of the edema at a dose of 100 ■ mg / kg body weight. When using i-methyl-5-phenylacetylpyrrole-2-acetic acid, Another preferred compound, at a dose of 100 mg / kg body weight, is 4 percent Suppression of edema observed.

The invention accordingly also relates to medicaments which contain a compound of the general formula I in the IU the group is -COOH.

The compounds of the general formula I can occur in stereoisomers (enantiomers) if the. ^ - carbon _{atom is substituted by a methyl group (R 2} = CH,). The (-) or (+) form of the corresponding compounds can be obtained by ubli- • before cleavage. These pharmacologically active enantiomers of the acids are also claimed.

The examples illustrate the invention.

Example i

A) i ^ -Cyclohexylcarbonyl-i-methylpyrrole-S-acetonitrile

A solution of 14.6 ml (0.1 mol) of cyclohexylcarbonyl chloride uni 12 g (0.1 mol) of i-methylpyrrole-2-acetonitrile in 100 ml of methylene

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Chloride is cooled to -25 ° C. Then the mixture is within 30 minutes with a solution of 11.3 ml of tin tetrachloride added in 40 ml of methylene chloride. After the addition has ended, the orange-colored suspension is allowed to warm to room temperature and then poured into dilute hydrochloric acid. The organic solution is separated off and successively with Ν, Ν-dimethyl-1,3-propanediamine, 3 & hydrochloric acid and saturated saline solution and then dried over magnesium sulfate. On that the solvent is distilled off. The remaining oil is digested with methanol and crystallized. The white crystals of iJ-Cyclohexylcarbonyl-i-methylpyrrole-2-acetonitrile are filtered off and recrystallized from methanol. M.p. 112 to 114 ° C.

B) The procedure according to Example 1 (A) is repeated, as Acy * However, an equivalent amount of cyclopentyl carbonyl chloride is used as the lating agent used. 5-Cyclopentylcarbonylimethylpyrrole-2-acetonitrile is obtained.

Example 12

A) SMSyclohexylcarbonyl-i-methylpyrrole ^ -acetic acid ^;

A solution of 5 g (0.022 mol) of 5-cyclohexylcarbonyl-i-methyl-5SJ3? A? Ol-2-acetonitrile in 44 ml of 1N sodium hydroxide solution and 40 ml of aqueous ethanol is refluxed for 18 hours. After cooling, the mixture is poured onto ice which has been acidified with dilute hydrochloric acid. The suspension obtained is extracted by shaking between the acid and chloroform. The chloro-

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form solution is separated and evaporated. The remaining oil is shaken between diethyl ether and 3N hydrochloric acid. The ether solution is extracted three times with saturated sodium bicarbonate solution. The basic fractions are combined and acidified with dilute hydrochloric acid. 5-Cyclohexylcarbonyl-1-methylpyrrole-2-acetic acid separates in white crystals, which are filtered off. M.p. 112.5 to 115 ° C. To Recrystallization from a mixture of diethyl ether and methylcyclohexane has a melting point of 113 "to 115 ° C.

B) According to Example 2 (A), but using an equivalent Amount of 5-cyclopentanoyl compound obtained in Example 1 (B), the corresponding 5-cyclopentylcarbony1-1-methylpyrrole-2-acetic acid is obtained.

Example 3 5-Cyclohexy lcarbony 1-1 -methy lpy r rol-2-acetic acid ethers

A suspension of 5 »2 g of aluminum chloride in 20 ml of methylene chloride is cooled to 5 ° C and 5 »? g cyclohexane carboxylic acid chloride offset. The mixture is then at 5 ° C in a Solution of 6.5 g of 1-methylpyrrole-2-acetic acid ethyl ester in 60 ml Methylene chloride was added dropwise. After the addition has ended, the reaction mixture is stirred for 20 minutes and at the temperature of the lower limit let warm up. Thereafter, the reaction gel is diluted in Poured hydrochloric acid. The organic solution is separated off and successively with Ν, Ν-dimethylaminopropylamine, diluted Hydrochloric acid and saturated saline solution. After that, will

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2Τ02671

the organic solution dried over magnesium sulfate and under evaporated under reduced pressure. The product is placed on a silica gel column purified by chromatography. The column is filled with hexane and then with a mixture of hexane and increasing proportions Benzene eluted. The first fraction, which contains a material that absorbs UV light, is evaporated to dryness. The specified product is obtained.

Example 4 5-Cyclohexylcarbonyl-1-methylpyrrole-2-acetic acid

A mixture of 0.01 mol of 5-cyclohexylcarbonyl-i-methylpyrrole-2-acetic acid ethyl ester in 12 ml (0.012 mol) of 1N sodium hydroxide solution and 5 ml of 95 percent ethanol is refluxed for 30 minutes , then cooled and diluted with water. The ethanol is then distilled off under reduced pressure. The solution is filtered and the filtrate is acidified with dilute hydrochloric acid. The precipitated crystals are filtered off, dried and the aqueous methanol is recrystallized. You get that specified product in pure form.

Example5 - ^:

The procedure of Example 3 is repeated, but an equivalent one Amount of 1,4-D3met% 1-pyrrole-2-acetic acid ethyl ester used. The product obtained is 5-cyclohexylcarbonyl-1,4-dimethylpyrrole-2-acetic acid ethyl ester. Subsequent hydrolysis according to Example 4- gives the Jp-Cyclohexylcarbonyl-I, 4- dimethylpyrrole-2-acetic acid.

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_ ₁₂ _- - ■ - ■ 2302S71

Examples

A) 5-Cyclohexylcarbonyl-1, oc-dimethylpyrrole-2-acetonitrile

2.24 g of 5-cycloliexylcarbonyl-1-methylpyrrole-2-acetoiiitrile become added to a suspension of 0.42 g of 57 percent sodium hydride in 30 ml of anhydrous dimethyl sulfoxide. After 30 minutes Stirring, the mixture is cooled in an ice bath, and 1.56 g of Me thy Ij οdid are added while stirring. The mixture is 30 minutes stirred, then poured into water and extracted with diethyl ether. The ether extract is saturated with saline washed, dried over magnesium sulfate and evaporated under reduced pressure. The specified product is obtained.

B) According to Example 6 (A '), but using an equivalent Amount of 5-cyclohexylcarbonyl-1,4-dimethylpyrrole-2-acetic acid ethyl ester, 5-cyclohexylcarbonyl-1,4, cC-trimethylpyrrole-2-acetic acid ethyl ester is obtained.

Example 7 5-Cyclohexylcarbonyl-1- * methylpyrrole-2-acetamide

A mixture of 2.24 g of 5-cyclohexylcarbonyl-1-methylpyrrole-2-acetonitrile and a solution of 0.4 g of sodium hydroxide in 20 ml of 95 percent ethanol is refluxed for 20 minutes. The solvent is then distilled off under reduced pressure and the residue is digested with water for crystallization. "The stated product is obtained. '-'.

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Example 8 5-Cyclohexylcarbonyl-1-methylpyrrole-2-acetic acid

A mixture of 0.015 mol of 5-cyclohexylcarbonyl-i-methylpyrrole-2-acetamide, 30 ml of a 1N sodium hydroxide solution and 30 ml of 95 percent Ethanol is refluxed and stirred for 6 hours. The ethanol is then distilled off under reduced pressure. The remaining solid is dissolved in water and the solution is filtered off from insoluble substances. The filtrate is with acidified with dilute hydrochloric acid. Crystalline 5-cyclohexylcarbonyl-i-methylpyrrole-2-acetic acid precipitates from that through. Recrystallization from a mixture of equal parts of acetone and Water is purified.

Example 9 A) 5-Cyclohexanoyl-pyrrole-2-acetonitrile

A suspension, cooled to -5 ° C., of 0.2 mol of aluminum trichloride in 110 ml of methylene chloride is treated dropwise with 0.2 mol of cyclohexyl chloride. The mixture is then added dropwise to a solution, cooled with a freezing mixture, of 0.2 mol of pyrrole-2-acetonitrile in 125 ml of methylene chloride. After the addition has ended, the reaction mixture is ^{stirred for a further 10 minutes at 0 °} C. and then poured into ice acidified with dilute hydrochloric acid. The precipitated 5-cyclo- > hexanoyl-pyrrole-2-acetonitrile is filtered off, washed with methanol and dried.

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B) 5-Cyclohexanoyl-pyrrole-2-acetic acid

The nitrile obtained in Example 9 C-A-) is according to Example 2 (A) saponified to nitrile. The specified product is obtained.

Example 10 -A-)! P-Cyclohexanoyl-i-ethylpyrrole ^ -acetonitrile

A mixture of 0.1 mol of 5-cyclohexanoyl-pyrrole-2-acetonitrile, 0.5 mole (4-1.7 S) potassium carbonate and 0.105 mole (16.1 g) ethyl iodide in 300 ml methyl ethyl ketone is refluxed for 12 hours cooked. The reaction mixture is then poured into water and extracted several times with chloroform. The chloroform extract is dried over magnesium sulfate and under reduced Evaporated pressure. The crystalline residue is recrystallized from isopropanol. The specified product is obtained,

B) 5-Cyclohexanoyl-1-ethylpyrrole-2-acetic acid

The compound is made by hydrolysis of the nitrile of Example (A) prepared according to Example 2 (A). ": ■

Example 111 A) 5-Cyclohexylearbony1-1, oc-dimethylpyrrole-2-acetic acid «. -

According to Example 2 (A), but using an equivalent amount of 5-cyclohexylcarbonyl-1, OC-dimethylpyrrole-2-acetonitrile _t one obtains the specified product. *

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_ 73Ό2671

B) ip-Cyclohexylcarbonyl-i, ^ -, ^ -trimethylpyrrole-2-acetic acid

According to Example 4-, however, using an equivalent Amount of ^ -Cyclohexylcarbonyl-I, ^ -, oC'-trimethylpyrrole-2-acetic acid ethyl ester, you get the specified product.

Example 12 1-Methyl-5-phenylacetylpyrrole-2-acetic acid

40.2 g (0.26 mol) of phenylacetyl chloride are added to a cooled suspension of 34.5 g (0.26 mol) of aluminum trichloride in 650 ml 1,2-dichloroethane given. The mixture is then within 20 minutes to a solution of 31.8 g (0.26 mol) of N-methylpyrr ^ l-2-acetonitrile added dropwise to 130 ml of 1,2-dichloroethane. The received Mixture is stirred for a further 4-0 minutes and finally Heated under reflux for 3 minutes. Each cooling, the mixture is poured onto ice acidified with hydrochloric acid. The organic solution is separated off and the aqueous solution with 1,2-dichloroethane extracted. The combined Dichlorathanlosungen are washed with water and with aqueous Ν, ΪΤ-Dimethylaminopropylaminiösung shaken. The organic solution will

separated and successively with dilute hydrochloric acid and saturated Washed brine, dried over magnesium sulphate and evaporated under reduced pressure. The leftover Oil (about 38 g) is chromatographed on 100 g of acid-washed aluminum oxide. The column is successively with staged Gradient mixtures of hexane, benzene and benzene diethyl ether eluted. The product is in the first eluate fractions, which absorb UV light, and it is optimal with a mixture of equal parts by volume of benzene and diethyl ether as Eluent received. The combined product fractions are evaporated. This leaves 11 g of a yellow oil which crystallizes on standing. After recrystallization from isopropanol as well a mixture of ethyl acetate and cyclohexane are 3.5 g of 1-methyl-5-phenylacetylpyrrole-2-acetonitrile with a melting point of 72 to 74 ° C obtain. ;

309830/1198 original inspected

3/4 g (0.143 mol) of the nitrile obtained are mixed with 28.6 ml of In Sodium hydroxide solution and 30 ml of ethanol refluxed for about 15 hours. Thereafter, the solvent is under reduced pressure distilled off and the residue dissolved in water and filtered. The filtrate is acidified with dilute hydrochloric acid. The precipitated one 1-Methyl-5-phenylacetylpyrrole-2-acetic acid is filtered off and air-dried.

Yield 3.6 g (94% of theory) of yellowish crystals. Mp 131-134 ° C (methanol).

Example 13

5-phenylacetyl-pyrrole-2-acetic acid

The compound mentioned is prepared according to Example 12, but using an equivalent amount of pyrrole-2-acetonitrile. Solvent mixtures are used for purifying chromatography eluted containing hexane, benzene, ether, chloroform and ethyl acetate. The 5-phenylacetyl-pyrrole-2-acetonitrile intermediate "is in the first eluate fractions, which absorb in UV light.

Example 14 1-methyl-5-phenylacetylpyrrole-2-acetic acid ethyl ester

5 g of 1-methyl-5-phenylacetylpyrrole-2-acetic acid in 100 ml of anhydrous ethanol containing 0.5 g of hydrogen chloride are refluxed for 1 hour. Thereafter, the solvent wlxä under reduced pressure distilled off. The ester remains behind.

Example 15 ■

Propyl 5-phenylacetylpyrrole-2-acetic acid

According to Example 14, but using 100 ml of n-propanol

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230267Ί

the corresponding propyl ester is obtained.

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Claims (1)

Claims 5-acylpyrroles of the general formula I ^R l-, ■ "■ - ^R 3 (I) in which IL benzyl, cyclopentyl or cyclohexyl group and R a hydrogen atom od * mean a lower alkyl radical, R and R _2, ^ie ^ are the same or different, represent hydrogen atoms or methyl groups, and R is the group -GOOH, -COO-C-lower-alkyl), -COKH ₂ or -CN, with the proviso that R is a lower alkyl radical when R. denotes a methyl group, R denotes the group -COOH or -COO- (lower-alkyl) when R denotes a methyl group, and S ,. ' and R _{2 represent} hydrogen atoms and R 1 represents the group -COOH, -COO- (lower-alkyl) or -CN when R 1 is the benzy group. 2. 5-Cyclohexanoylpyrrole-2-acetic acids of the general formula 2 CPt-COOH in which R denotes a hydrogen atom or a lower alkyl radical and R. and R ₂ , which are identical or different, represent hydrogen or methyl groups, where Rp is a methyl group when R represents a lower alkyl radical, 3 0 9 8 3 0/1198 3 · 5-Cyclohexanoylpyrroles of the general formula ^R l in which R is a hydrogen atom or a lower alkyl radical ", E. and Rp, which are identical or different, are hydrogen or methyl groups and R ^{1 is} the group -COO- (lower-alkyl), -COEH ₂ or -CN , with the proviso that R represents a lower alkyl radical when Rg is a methyl group and when R. is a methyl group, R ^{1 represents} the group -COO- (lower-alkyl). 5-Cyclohexanoyl-1-methylpyrrole-2-acetic acids of the general formula -4 μJ ^C0 -4 µ JL 4 "H-COOH CH, 5 in the R ^ and Rp, which are the same or different, Wasserst off mean atoms or methyl groups. 5 x 5-cyclohexanoyl-1-methylpyrrole-2-acetic acid. 6. 5-Cyclohexanoy1-1, c * -dimethylpyrrole-2-acetic acid. 7 · 5-Cyclohexanoy1-1,4-dimethylpyrrole-2-acetic acid. 309830/1198 2302871 8. 5-Cyclohexanoyl-1,4-, (? C; -trimethylpyrrole-2-acetic acid. 9 · 5-Cyclohexanoyl-1-methylpyrrole-2-acetonitrile. 10. 5-Cyclohexanoyl-1-methylpyrrole-2-acetic acid-lower-alkyl ester 11. ^ -Cyclohexanoyl-i-methylpyrrole - ^ - ethyl acetate. 12. i-Methyl - ^ - phenylacetylpyrrole ^ -acetic acid. 13. i-Methyl - ^ - phenylacetylpyrrole ^ -acetic acid-lower-alkyl ester. 14.; i ~ Methyl-5-phenylacetylpyrrole-2-ethyl acetate. 15. Propyl 5-i'lienylacetylpyrrole-2-acetic acid. 16. 5-Rienylacetylpyrrole-2-acetonitrile of the general formula JTT // - ° ^Η 2-00- ^ ρ - ^ - CH ₂ -CN in which R is a hydrogen atom or a methyl group, 17. i-methyl - ^ - phenylacetylpyrrole - ^ - acetonitrile. 18. Process for the preparation of 5-acylpyrroles of the general Formula I ^ l Ii-R ₃ (i) 309830/1198 in which R ^ denotes the benzyl, cyclopentyl or cyclohexyl group and R denotes a hydrogen atom or a lower alkyl radical, R and R ₂ , which are identical or different, denote hydrogen atoms or methyl groups and R denotes the group -COOH, -COO-C-lower- Alkyl), -CONH or -CN, with the proviso that R is a lower alkyl radical when R is a methyl group, R is the group -COOH or -COO-C-lower-alkyl) when R ^ is a methyl group, and R and R represent hydrogen atoms and R denotes the group -COOH, -COO- (lower-alkyl) or -CN, when R ^ is the benzyl group, characterized in that one (a) an acyl halide of the general formula , .0 R ^ -C-hal in which hai represents a halogen atom, with a compound of the general formula III (III) in which R ^{1 represents} the group -COO-C-lower-alkyl) or -CIi- . that,
represents, with the proviso, / if R ^{1 is} the group -CN, R denotes a hydrogen atom, and with the further ^η that,
Provided that R. is the benzyl group, R ^{1 is} the group -CN, in the presence of a Lewis acid and in a solvent to give a compound of the general formula IV 309830/1198 _Often) G, NAt "B. implements or Cb-) a compound prepared according to (a) of the general
Formula V Λί Ji- \ lower-alkyl) CH ₂ -E ' (J) in which η has the value 1 or 2, C-methylated in a manner known per se to give a compound of the general formula GH. CH-R ¹ lower alkyl) or (c) a compound of the general formula (CH ₂ ! I. -CH ₂ -CN in which η has the value 1 or 2, 1-alkylated in a manner known per se to give a compound of the general formula (lower alkyl) 309830/1198 OBlGtHM- IHSPECTED or (d) The compound produced according to (c) is known per se Way C-methylated to a compound of general formula ( ^cH ?> A „π Ρ ³ Λ-CH — CN (lower-alkyl) or (E) one of the compounds obtained according to (a) and (b) with the radical R ¹ saponified in a manner known per se to give a compound of the general formula 3 ^] JUh-COO or
(f) a compound of the general formula CH-CN in a manner known per se to the acid amide of the general formula (CH ₂ ) TT μ -U-CH-. CONH ₂ 309830/1 198 saponified or (g) a compound of the general formula (CH ₂ W _CH—- COO- (lower-alkyl) in a manner known per se with ammonia into the acid amide of the general formula . . \ ~ CGU ^ ~ ^ R CH-CONHg converted or (h) a compound of the general formula ■ Cjl > - COOH in a manner known per se, with a lower aliphatic Alcohol to the ester of the general formula J-C H _o -C00 (lower-alkyl) implements. Process for the preparation of 5-cyclohexanoyl-i-methylpyrrole-2-acetic acid, characterized in that the corresponding 2-acetonitrile is saponified to give the free carboxylic acid. 309830/1198 20. Process for the preparation of 5-cyclohexanoyl-1, c * .- dimeth; ylpyrrole-2-acetic acid, characterized in that the corresponding 2-acetonitrile is saponified to give the free carboxylic acid. 21. Process for the preparation of 5-Cyclohexanoy1-1,4-dimethy1-pyrrole-2-acetic acid, characterized in that the corresponding 2-acetic acid-lower-alkyl ester is converted into the free carboxylic acid saponified. 22. Process for the production of 5-cyclohexanoyl ~ 1,4, <* - trimethylpyrrole-2-acetic acid, characterized in that the corresponding 2-acetic acid-lower-alkyl ester to the free Saponified carboxylic acid. 23. Process for the preparation of 5-cyelohexanoyl-i-methylpyrrole-2-acetonitrile, characterized in that one uses cyclohexylcarbonyl chloride with i-methylpyrrole-2-acetonitrile after Friedel-Crafts implements. 24. Process for the preparation of ^ -Cyclohexanoyl-i-methylpyrrole-2-acetic acid ethyl ester, characterized in that one cyclohexanecarbonyl chloride with i-methylpyrrole-2-acetic acid ethyl ester implemented according to Iriedel-Crafts. 25. Process for the preparation of 1-Methy1-5-phenylacety! Pyrrole- ■ \ 2-acetic acid, characterized in that the corresponding 2-acetonitrile is saponified. 309830/1198 26. Process for the preparation of i-methyl-5-phenylacetylpyrrole-2-acetic acid ethyl ester, characterized in that the corresponding 2-acetic acid is esterified with ethanol. 27. Process for the preparation of 5-phenylacetylpyrrole-2-acetic acid propyl ester, characterized in that the corresponding 2-acetic acid is esterified with n-propanol. 28. Process for the preparation of i-methyl-5-phenylacetylpyrrole-2-acetonitrile, characterized in that phenylacetyl chloride with H-methylpyrrole-2-acetonitrile according to Friedel-Crafts implements. 29. Medicines containing a compound of the general. Formula I according to claim 1, in which R is the group -COOH, and customary carriers and / or diluents and / or auxiliaries. 309 8 30/1198