NO139386B - ANALOGICAL PROCEDURE FOR THE PREPARATION OF PHARMACOLOGICALLY ACTIVE IMIDAZOPYRIDINES - Google Patents

Description

The present invention relates to the preparation of new imidazo[4,5-b]pyridines with the general formula I

where

means an alkylamino-, dialkylamino-, hydroxy-, allyloxy-, benzyloxy-, alkylthio-, alkylsulfinyl-, alkylsulfonyl-,

morpholino, N-phenylpiperazino or N-alkylpiperazino group,

or an alkoxy group- which may be "substituted with a halogen-

atom, a hydroxy-, alkoxy-, alkylthio-, alkylsulfinyl-, alkylsulfonyl-, alkylamino-,.dialkylamino-, piperidino-,

morpholino-, thiomorpholino-, N-alkylpiperazino-, N-phenylpiperazino-, N-methoxy-phenylpiperazino-, N-phenylethyl1-piperazino-, phenylethyl-

amino-, N-methyl-phenylethylamino- or N-methyl-dimethoxyphenyl-ethylamino group,

R2 means a hydrogen or halogen atom, a methyl, hydroxy,

alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl group,

R 3 means a hydrogen atom or an alkoxy group,

or two of the radicals R-^ to R^ together mean a methylenedioxy group,

R^ means a hydrogen atom, one optionally with a hydroxy-, dialkyl-

amino, phenyl, dimethoxyphenyl, piperidino, morpholino, 4-methylpiperazicho or 4-phenylpiperazino group substituted. alkyl residue, or a phenyl residue optionally substituted with halogen atoms or methoxy groups, and

R 5 means a hydrogen or halogen atom or an alkyl residue, the indicated alkyl, alkylthio, alkoxy, alkylsulfinyl and alkylsulfonyl residues containing 1-4 carbon atoms,

' and physiologically compatible acid addition salts thereof with inorganic or organic acids.

The compounds of the general formula I have valuable pharmacological properties, in particular an effect on blood pressure, cardiac strength, a positive inotropic effect, an antiulcer effect, an inhibitory effect on platelet agglomeration and increase the bleeding time, and are prepared by:

Reacts a pyridine of the general formula II

where

Rg is as stated above, and

Y means a halogen atom or an R4~NH group, where R4 is as indicated above, with a compound of the general formula III

where

R^ to R^ are as indicated above, and

X means a carboxyl group or a functional derivative thereof.

Examples of functional acid derivatives are a nitrile, acid halide, ester, amide, imidic acid ester, imidic acid thioester, imidic acid halide, amidine, thiocarbonic acid, dithiocarbonic acid, N-carbonic acid anhydride or orthoester derivative.

The reaction is suitably carried out in a suitable solvent such as benzene, pyridine, glycol, toluene, acetone, diethylene glycol or triethylamine, optionally in the presence of an acid binding agent such as pyridine or triethylamine, optionally in the presence of a catalytic amount of an acid, such as p -toluenesulfonic acid or possibly in the presence of .

of a water-attracting agent such as phosphorus oxychloride or thionyl chloride and is carried out according to the reactivity of the residue X

at temperatures between -20 and 250°C. However, the reaction can be carried out without a solvent.

If X e.g. is a carboxyl group or an amide derivative, the reaction is conveniently carried out in the presence of phosphorus oxychloride or thionyl chloride, and. optionally in the presence of a tertiary organic base, such as pyridine or triethylamine, preferably at temperatures between -20° and the boiling point of the solvents used, e.g. at 120°S.

If X e.g. means a nitrile group, . then the reaction is conveniently carried out in the presence of a catalytic amount of an acid, such as p-toluenesulfonic acid, preferably at temperatures between 120 and 180°C, e.g. at 160°C, possibly in a solvent.

If X e.g. means a thioamide derivative, then the reaction is conveniently carried out in a solvent such as glycol and preferably at temperatures between 100 and 150°C, e.g. at 130°C.

If Y in a compound according to the general formula II means a halogen atom, e.g. a chlorine atom, then the reaction proceeds over the corresponding amidine, which does not need to be isolated and which cyclizes at elevated temperatures, e.g. at temperatures between 100 and 200°C.

The compounds of the general formula I which are obtained according to

present invention, and which has a reactive halogen atom,

can then, if desired, be transferred with an amine to the corresponding amino compound, and/or obtained compounds of the form I which contain reactive hydrogen atoms, can then be alkylated with the aid of a base and a common alkylating agent, and/or obtained compounds with the general formula I can be transferred to the corresponding N-oxide, S-oxide or S,S-dioxide compounds by means of common oxidizing agents, and/or transferred to physiologically compatible acid addition salts with inorganic or organic acids. Examples of suitable acids are hydrochloric acid, hydrogen bromide, sulfuric acid, lactic acid, citric acid, tartaric acid, maleic acid or fumaric acid.

The starting materials used according to the present invention are known from the literature or can be produced according to known methods (see the examples).

As indicated above, the new compounds of the general formula I have valuable pharmacological properties, in particular an effect on blood drawn, a positive inotropic effect., a. anti-ulcer effect, an inhibitory effect on platelet agglomeration and prolongs bleeding time.

The following compounds were examined with regard to biological effects: A = 2-(2,4-dimethoxyphenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride,

B = 2-[2-(2-methylsulfinyl-ethoxy)-4-methoxyphenyl]-1H-imidazo[4,5-b]-pyridine hydrogen chloride,

C = 2-(2-methoxy-4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride,

D = 2-(2-methoxy-4-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride,

E = 2-(2-methoxy-5-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride,

F = 2-(2-methoxy-4-methyl-phenyl)-1H-imidazo4,5-b]pyridine hydrogen chloride,

G = 2-(2-ethoxy-4-methoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride,

H = 2-(2-ethoxy-4-methyl-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride,

1=2-(2-methoxy-4-chloro-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride and

J = 2-[2-(2-methylsulfinyl-ethoxy)-4-methylmercapto-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride.

N = 2-(2,4-dimethoxyphenyl)-7-methyl-1H-imidazo[4,5-b]pyridine hydrochloride,

0=2-(4-methylmercapto-phenyl)-3-(3-morpholino-propyl)-3H-imidazo-[4,5-b]pyridine

Comparative compounds (J. org. Chem. 29^, 3403-3405 (1964)):

K = 2-phenyl-1H-imidazo[4,5-b]pyridine hydrochloride,

L = 2-(4-methylphenyl)-1H-imidazo[4,5-b]pyridine,

M = 2-(4-Chlorophenyl)-1H-imidazo[4,5-b]pyridine hydrochloride.

1. Positive inotropic effect on isolated guinea pig atria:

Isolated guinea pig atria were placed in a 100 ml organ bath. The bath was filled with Tyrod solution, and had a temperature of 30 C. The Tyrod solution was bubbled through with carbogen (95% O2 and 5% C02). The spontaneous contraction of the atria was recorded isometrically with a Stathem force transducer on a Grass polygraph. The antechambers were loaded with 1 g. After sufficient equilibration time, the compounds to be investigated were added to the organ bath. -5 The concentration of the compounds in the organ bath was 1 x 10 g/ml. For each compound, 5 prechambers were used.

The test results appear in the following table:

2. Circuit experiments on anesthetized cats:

Cats were anesthetized intravenously with 30 mg/kg pentobarital sodium. A plastic catheter was inserted into the femoral artery and a steel catheter was inserted into the left ventricle from the carotid artery. With a Statham pressure recording device of the type P2 3AA and P2 3Dc, the arterial blood pressure and the pressure in the left ventricle were recorded continuously. From the ventricular pressure curve, the contractility parameter ^p/dt^^g and VCE were continuously calculated

using an analog computer. The heart rate was examined with a tachograph based on the ventricular pressure curve. In addition, the ECG was recorded in "II. Ableitung".

All recordings were performed using a brush direct recorder• The compounds were injected using a "vena cannula in the vena femoralis. Compounds A-J and L were examined on

3 cats, and N, 0, K and M of 2 cats.

The values found appear in the following table:

Finally, it should be noted that all compounds show no toxic side effects in the doses used.

The new compounds with the general formulas I and Ia can be processed for pharmaceutical applications, possibly in combination with other active compounds, into the usual preparation forms such as tablets, dragees, suppositories, ampoules or drops. The single doses are 35 to 200 mg, preferably 50 to 100 mg.

The following examples illustrate the invention:

Example 1

2-(2,4-Dimethoxyphenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

54.5 g of 2,3-diaminopyridine and 91.1 g of 2,4-dimethoxybenzoic acid were pulverized to a fine powder and added portionwise with stirring to 1500 ml of phosphorus oxychloride. After the addition was finished, it was heated for 2 hours under reflux, and then phosphorus oxychloride was distilled off in vacuum. The residue was triturated with 2000 ml of 2N hydrochloric acid, the solid product that precipitated was filtered off and recrystallized from water. Yield: 121 g (85% of theoretical), m.p. 238°C

Example 2

2-(2,4-Dimethoxyphenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

260 mg of 2,4-dimethoxybenzoic acid was dissolved in 2 ml of pyridine and a solution of 220 mg of 2,3-diaminopyridine in 2 ml of pyridine was added, whereby the corresponding salt precipitated. While stirring and ice-cooling, 0.38 ml of phosphorus oxychloride was added dropwise and stirred for a further 1 hour at 0°C and 1 hour at room temperature. Excess pyridine is then removed in a vacuum, the residue is taken up with dilute hydrochloric acid, neutralized with caustic soda and extracted with acetic acid. The acetic ester phase is evaporated, the residue is treated with a little 2N hydrochloric acid, the precipitate is filtered off and recrystallized from water.

Melting point: 2 38-2 39°C.

Example 3

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4>5-b] pyridine- hydrogen chloride

Was prepared analogously to example 2 from 2,3-diaminopyridine, 2,4-dimethoxybenzoic acid and thionyl chloride.

Melting point: 238-239°C.

Example 4

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

900 mg of 2,4-dimethoxy-benzoic acid was transferred to acid-

the chloride by heating in a mixture of 3 ml of benzene and 2 ml of thionyl chloride. It was then concentrated in vacuo and the residue was taken up in 5 ml of benzene. This solution was added dropwise with stirring to a solution of 550 mg of 2,3-diaminopyridine in 5 ml of pyridine. After the addition has been completed, it is heated briefly at 60°C, then cooled to room temperature, 0.9 ml of phosphorus oxychloride is added dropwise and stirring is continued for a further 3 hours at room temperature. 2 N hydrochloric acid is then added, neutralized and extracted with vinegar. The acetic ester phase is evaporated and a little 2N hydrochloric acid is added to the residue, the crystals that precipitate are sucked off and recrystallized from water.

Melting point: 237-238°C.

Example 5

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

a) 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrogen chloride 530 mg of 2,4-dimethoxybenzoic acid is transferred into the acid chloride analogously to example 4 and this is dissolved in 1 ml of benzene. This solution is added dropwise to a mixture of 440 mg of 2,3-diaminopyridine, 3 ml of pyridine and 2 ml of triethylamine and the whole is stirred for another 2 hours at room temperature. The mixture is then added to water, neutralized with concentrated hydrochloric acid and extracted with acetic acid. The acetic ester is evaporated, the residue is treated with dilute hydrochloric acid,

the crystals that fall out are sucked off and recrystallized from ethanol.

Melting point: 172-174°C.

b) 2-(2,4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride 155 mg of 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrogen chloride was dissolved in 2 ml of pyridine. 0.2 ml of phosphorus oxychloride was added dropwise to the mixture while stirring at room temperature. After 2 hours, pour the mixture into water and proceed analogously to example 4.

Melting point: 237-238°C

Example 6

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

155 mg of 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrogen chloride was heated for 5 minutes at 200-210°C. It was then treated with a little 2N hydrochloric acid, filtered and recrystallized from water.

Melting point: 237-238°C.

Example 7

2-(2,4-dimethoxy-phenvl)-1H-imldazo[4,5-blpyridine-hydrogen chloride

155 mg of 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrogen chloride was heated in 2 ml of glycol for 30 minutes under reflux. It was then diluted with water, neutralized, extracted with vinegar and worked up analogously to example 4. Melting point: 238-239°C.

Example 8

2-( 2 , 4- dimethoxy- phenyl) ^ lH- lmidazo[ 4, 5-" b] pyridine- hydrogen chloride

To 150 ml of phosphorus oxychloride, 5.45 g of 2,3-diaminopyridine was simultaneously added in small portions while stirring, and 9.81 g of 2,4-dimethoxybenzoic acid methyl ester was added dropwise. After the addition was finished, it was heated to 120°C. After 2 hours, the phosphorus oxychloride was evaporated in vacuo; the residue was digested with 2N hydrochloric acid and the solid final product was filtered off and recrystallized from water.

Melting point: 238-239°C.

Example 9

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

To 470 mg of 2,4-dimethoxybenzoyl chloride in 6 ml of toluene

0.5 ml of morpholine was added while stirring. After 20 minutes the toluene was evaporated, the residue was treated with dilute hydrochloric acid and this mixture was extracted with acetic acid. After washing the acetate phase with bicarbonate solution and concentration, crude 2,4-dimethoxybenzoylmorpholine is obtained as an oil. This was taken up in 5 ml of pyridine, 250 mg of 2,3-diaminopyridine was added and finally, with stirring and ice-cooling, 1 ml of phosphorus oxychloride was added dropwise. After stirring for 5 hours at 0°C, ice water was added, made alkaline with concentrated ammonia, heated for a short time on a steam bath and extracted with acetic acid. The acetic ester was evaporated, the residue obtained was treated with 2N hydrochloric acid, sucked off and recrystallized from water.

Melting point: 238°C.

Example 10 2-(2,4-dimethoxyphenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

300 mg of 2,4-dimethoxybenzoic acid (4-chloroanilide) and 110 mg of 2,3-diaminopyridine were mixed together and, with stirring, added in portions to 3 ml of phosphorus oxychloride. It was then heated for 8 hours under reflux, then phosphorus oxychloride was sucked off in vacuo,

the residue was triturated with 2N hydrochloric acid, the solid product obtained was filtered off and recrystallized from water.

Melting point: 237-238°C.

Example 11

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

600 mg of 2,4-dimethoxybenzoic acid (4-chloroanilide) was heated for 3 hours in a mixture of 5 ml of benzene and 2 ml of thionyl chloride under reflux. After evaporation, impure 2,4-dimethoxy-N-(4-chlorophenyl)-benzimidic acid chloride is obtained as an oil. This is taken up in 9 ml of toluene and added to a solution of 200 mg of 2,3-diaminopyridine in 10 ml of isopropanol and the mixture is heated for 10 minutes at 70°C. The obtained 2,4-dimethoxy-benzoic acid-N-(4-chlorophenyl)-N'-(2-amino-3-pyridyl)-amidine hydrogen chloride is not isolated, but taken up after evaporation of isopropanol in vacuum with 20 ml of glycol and heated under reflux for 10 minutes. Water is then added, made alkaline with concentrated ammonia, extracted with vinegar and worked up analogously to example 4.

Melting point: 237-238°C.

Example 12

2-( 2, 4- dimethoxy- phenyl)- 1H- imidazo[ 4, 5- bIpyridine- hydrogen chloride

100 mg of 2,3-diaminopyridine, 200 mg of 2,4-dimethoxybenzonitrile and 400 mg of p-toluenesulfonic acid monohydrate are mixed and heated for 3 hours at 160°C. The product is then shredded with dilute ammonia and vinegar until everything is dissolved. The aqueous phase is extracted once more with vinegar. The combined acetic ester fractions are extracted. with a little 2N hydrochloric acid, and the product crystallizes out after a while. Melting point: 237-238°C.

Example 13

2-(3,4,5-trimethoxyphenyl)-1H-imidazo[4,5-b]pyridine

3.4 g of p-toluenesulfonic acid monohydrate and 15 ml of benzene are heated at 120°C until all the benzene has evaporated. Then 1.1 g of 2,3-diaminopyridine and 2 g of 3,4,5-trimethoxybenzoic acid nitrile are added and the mixture is heated for 2 hours at 150°C. After cooling, water is added, extracted with ethyl acetate, the ethyl acetate phase is washed with dilute caustic soda, concentrated and the residue recrystallized from isopropanol/petroleum ether.

Melting point: 226°C.

Example 14

2-(3,4,5-trimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine

A mixture of 4.2 g of 3,4,5-trimethoxybenzoic acid and 2.2 g of 2,3-diaminopyridine is boiled for 2 hours in 40 ml of phosphorus oxychloride under reflux. Phosphorous oxychloride is then separated off, ice water is added to the residue and the solid product that precipitates is filtered off. The product is dissolved in hot water, made alkaline with concentrated ammonia, the precipitate is filtered off and recrystallized from a little isopropanol.

Melting point: 225-226°C.

Example 15

2-(2,5-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine

a) 2, 5-dimethoxy-thiobenzoic acid morpholide

A mixture of 10 g of 2,5-dimethoxybenzaldehyde, 10 g of morpholine

and 4 g of sulfur are heated at 130°C for 3^ hours and then dissolved in 300 ml of hot etaphthol. The product which precipitates on cooling is recrystallized from ethanol.

Melting point: 127°C.

b) S- methyl- 2, 5- dimethoxy- thiobenzoic acid- morpholide- iodide

6 g of 2,5-dimethoxythiobenzoic acid morpholide, 6.5 g of methyl iodide and 30 ml of acetone are heated under reflux for 8 hours. The solid product that has precipitated is then filtered and washed with ether and used directly for further conversion.

c) 2-(2,5-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine

2 g of S-methyl-2,5-dimethoxy-thiobenzoic acid morpholide iodide and

1.1 g of 2,3-diaminopyridine is heated at 130°C in 30 ml of glycol for 40 minutes. It is then poured into ice water, filtered off and recrystallized from ethanol/water.

Melting point: 235°C.

Example 16

2-(4-hydroxy-phenyl)-1H-imidazo[4,5-b]pyridine

a) 4-hydroxy-thiobenzoic acid morpholide

Prepared analogously to Example 15a from 12.2 g of 4-hydroxybenzaldehyde, 16 g of morpholine and 3.2 g of sulfur.

Melting point: 205°C.

b) S- methyl- 4- hydroxy- thiobenzoic acid^ morpholide- iodide

Prepared analogously to example 15 b from 14.4 g of 4-hydroxythiobenzoic acid morpholide and 2.1 g of methyl iodide in 100 ml of acetone. Melting point: 181°C.

c) 2-(4-hydroxy-phenyl)-1H-imidazo[4,5-b]pyridine

1.84 g of S-methyl-4-hydroxy-thiobenzoic acid morpholide iodide were

heated with 1.1 g of 2,3-diaminopyridine in 30 ml of glycol for 20 minutes at 130°C. The product which precipitates on cooling was poured into caustic soda and precipitated with acid.

Analysis: Calculated: 65.87% C 5.13% H 16.46% N

Found: 65.90% C 5.16% H 16.47% N.

Example 17

2-[ 4- methoxy- 2-( 3- chloropropoxy)- phenyl]- 1H- imidazo[ 4, 5- b pyridine hydrogen chloride

a) 4- methoxy- 2-( 3- chloro- propoxy)- benzoic acid morpholide

21.9 g of 2-hydroxy-4-methoxy-benzoic acid morpholide was dissolved

1,200 ml/dimethylformamide and added 11.2 g of potassium tertiary butylate. After everything was dissolved, 50 g of 1-chloro-3-bromopropane was added and then heated at 130°C for 2 hours. It was then evaporated in vacuo, the residue was taken up in ethyl acetate, washed with caustic soda and water and evaporated and used without further purification. b) 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrochloride 20 g 4-methoxy-2-(3-chloro-propoxy)-benzoic acid -morpholide, 7 g of 2,3-diamino-pyridine and 170 ml of phosphorus oxychloride are heated for 2 hours under reflux. After evaporation of phosphorus oxychloride, the residue was added to water, neutralized with caustic soda, extracted with acetic acid and the hydrogen chloride was precipitated with ether/hydrochloric acid. Melting point: 198°C (decomposition).

Example 18

2-[ 4- methoxy- 2-( 2- chloroethoxy)- phenyl]- 1H- imidazo[ 4, 5-b] pyridine hydrochloride

a) 4- methoxy- 2-( 2- hydroxy- ethoxy)- benzoic acid morpholide

23.7 g 2-hydroxy-4-methoxy-benzoic acid morpholide, 33.6 g

potassium tertiary butylate and 37.4 g of ethylene bromohydrin were heated in 100 ml of dimethylformamide for 6 hours at 120°C. After concentration in vacuum was taken up in chloroform, washed with caustic soda and water and concentrated.

b) 2-[ 4- methoxy- 2-( 2- chloroethoxy)- phenyl3- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

2.8 g of 4-methoxy-2-(2^hydroxy-ethoxy)-benzoic acid morpholide, 1.1 g of 2,3-diaminopyridine and 20 ml of phosphorus oxychloride are boiled for 2 hours

during reflux. After evaporation, water was added, neutralized, extracted with ethyl acetate and the hydrogen chloride was precipitated with ether/hydrochloric acid.

Melting point: 110°C (decomposition).

Example 19 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrochloride

a) 4- methoxy- 2-( 3- chloropropoxy)- benzoic acid anilide

2.5 g of 2-hydroxy-4-methoxy-benzoic acid anilide, 5 ml of 1-chloro-3-bromopropane, 1.12 g of potassium tertiary butylate and 20 ml of dimethylformamide were heated for 2 hours at 130°C. It was then evaporated in vacuo, water was added and filtered off.

Melting point: 87-90°C

b) 2-[ 4- methoxy- 2-( 3- chloropropoxy)- phenyl]- 1H- imidazo[ 4, 5- bjpyridine hydrogen chloride

Prepared analogous example 17b from 4-methoxy-2-(3-chloro-propoxy)-benzoic acid anilide and 2,3-diamino-pyridine. Melting point: 198°C...

Example 20 2-[4-methoxy-2-(3-morpholino-propoxy)-phenyl3-1H-imidazo[4,5-b]-pyridine

0.5 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenyl3-1H-imidazo-[4,5-b]pyridine hydrogen chloride was heated under reflux with 5 ml of morpholine for 4.5 hours. Water was then added, filtered and

recrystallized from water. W; Melting point: 108-110°C.

Example 21 2-[4-Methoxy-2-(2-(4-phenyl-1-piperazinyl)-ethoxy)-phenyl]-1H-imidazo[4,5-bIpyridine

Prepared from 1.7 g of 2-[4-methoxy-2-(2-chloroethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and 3.2 g of 1-phenylpiperazine by 8 hours boiling in ethanol. Melting point: 164-165°C (from isopropanol).

Example 22 2-[4-methoxy-2-(3-dimethylamino-propoxy)-phenyl]-1H-imidazo[4,5-b]-pyridine hydrogen chloride

1.8 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]-pyridine hydrogen chloride and 20 ml of saturated dimethylamino solution in ethanol were heated for 8 hours in a bomb at 100°C... It was then evaporated

to vacuum and recrystallized from isopropanol.

Melting point: 209-210°c.

Example 23

2-1 4-Methoxy-2-(3-dimethylamino-propoxy)-phenyl3-1H-imidazo! 4, 5-b]-pyridinedihy. drug chloride

1.64 g of 4-methoxy-2-(3-dimethylamino-propoxy)-thiobenzoic acid morpholide was dissolved in a mixture of 17 ral of glacial acetic acid and 3 ml of acetic anhydride, 1 ml of dimethyl sulphate was added and heated for 1 hour on a steam bath. It was then evaporated in vacuo. The crude S-methyl-4-methoxy-2-(3-dimethylamino-propoxy)-thiobenzoic acid morpholide methyl sulfate obtained was taken up in 13 ml of glycol, 0.7 g of 2,3-diaminopyridine was added and heated for 2 hours at 160° C. The whole was poured into 50 ml of water, 5 ml of concentrated ammonia was added and extracted with acetic acid. The acetate phase was evaporated, the residue was taken up in ethanol, ether/hydrochloric acid was added and evaporated again. The residue was triturated with toluene and some ethanol. It is suctioned off and recrystallized from isopropanol.

Melting point of the dihydrochloride hydrate: 228-235°C (decomposition).

Example 24

2-(2,4-dimethoxy-phenyl)-3-methyl-3H-imidazo[4,5-b]pyridine

800 mg of 2,4-dimethoxybenzoic acid methylamide was heated with 500 mg of 2-chloro-3-aminopyridine in 10 ml of phosphorus oxychloride for 3 hours under reflux. The whole was poured into water, neutralized with ammonia and extracted with vinegar. After evaporation, impure N-methyl-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine is obtained, which is taken up in 10 ml of 10% glycol/sodium lye and heated for 4 hours at 180-190 °C. The mixture is poured onto water, extracted with acetic acid and purified over a column (sieve gel, eluent CHC13 : MeOH = 19 : 1). Melting point for the hydrogen chloride: 196-197°C.

Example 25 2-(2,4-dimethoxy-phenyl)-3-(4-chlorophenyl)-1H-imidazo[4,5-b]pyridine

.3 g of 2,4-dimethoxy-benzoic acid-(4-chloroanilide) and 1.3 g of 2-chloro-3-aminopyridine were heated in 16 ml of phosphorus oxychloride for 2 hours under reflux. The mixture was poured onto water, neutralized with concentrated ammonia and extracted with acetic acid. The acetate phase was extracted with 3N hydrochloric acid. After neutralization of the aqueous phase, it was again extracted with vinegar. The remaining solid product after evaporation was recrystallized from methanol. Melting point: 176-178°C.

Example 26 2-(2,4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride "2.2 g of 2,3-diaminopyridine, 6.8 g of imide chloride of 2,4-dimethoxy- Benzoic acid morpholide and 12 ml of triethylamine were heated in 10 ml of diethylene glycol dimethyl ether for 1 hour at 120° C. After cooling, the reaction mixture was added to water, extracted with chloroform and the chloroform phase was shaken. with ammonia and purified by means of column chromatography.. The hydrogen chloride is precipitated once again from acetone with ether/hydrochloric acid.Melting point: 237-238°C.

Example 27 2-(2,4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

From 1.1 g of 2,3-diaminopyridine and 3.5 g of 2,4-dimethoxybenzoic anhydride by heating for 5 hours at 180°C. Processing takes place analogously to example 26.

Melting point: 236-2 38°C.

Example 28

2-(2-Methoxyphenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

a) 2-Methoxy-"thiobenzoic acid morpholide 34 g 2-methoxybenzaldehyde, 16 g sulfur and 32.6 g morpholine

..was heated for 3 hours at 120°C. The resulting reaction mixture is taken up in ethanol, filtered, cooled and the yellow crystals that

falling out is sucked from.

Yield: 54.1 g (91% of theoretical), melting point: 80-82PC.

b) 2-Methoxythiobenzoic acid morpholide methiodide 47.4 g of 2-methoxythiobenzoic acid morpholide are heated under

reflux in 150 ml of acetone with 25 ml of methyl iodide for 1 hour and the yellow crystals that precipitate on cooling are sucked off.

Yield: 64.4 g (85% of theoretical), melting point: 162-164°C.

c) 2-(2-Methoxyphenyl)-1H-imidazo[4,5-b]pyridine

19 g of 2-methoxythiobenzoic acid morpholide methiodide and 8.7 g.

2,3-diaminopyridine is heated in 70 ml of glycol for 3 hours at 120°C. After cooling, water is added, made alkaline with ammonia and extracted with chloroform. The organic phase is washed with water and then 2N hydrochloric acid is added. The product that falls out is sucked from,

the base is liberated again with ammonia, taken up in chloroform and purified : :>ver a silica gel column. Colorless hydrogen chloride is obtained

from acetone by adding ether/hydrochloric acid.

Melting point: 233-234°C.

Example 29

2-(2- methoxyphenyl)- 3- methyl- 3H- imidazo[ 4, 5- biPyridln- hydrogen chloride

Prepared analogously to Example 28 from 2-methylamino-3-amino-pyridine and 2-methoxy-thiobenzoic acid morpholide methiodide. Melting point: 208-210°C.

Example 30 2-[2-(2-Methoxyethoxy)phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogous example 28 from 2-(2-methoxyethoxy)-liobenzoic acid morpholide methiodide and 2,3-diaminopyridine.

Melting point: 170-172°C.

example 31,:

2-(4-Methoxyphenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

Prepared analogously to Example 28 from 4-methoxythiobenzoic acid i.orpholide methiodide (melting point: 142-144°C) and 2,3-diaminopyridine. Melting point: 243-245°C.

Example 32 '.-(3-Methoxy-4-hydroxy-phenyl)-1H-imidazo [4,5-bjpyridine hydrogen chloride

Prepared analogously to example 28 from 3-ethoxy-4-hydroxy-iobenzoic acid morpholide methiodide (melting point: 178-180°C) and 1,3-diaminopyridine.

Melting point: 251-254°C.

Example 33

2-( 2, 3- dlmetboxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

Prepared analogously to Example 28 from 2,3-dimethoxy-thiobenzpeic acid-.thiopholide-methiodide (melting point: 138-140°C) and 2,3-diaminopyridine. Melting point: 270-272°C.

Example 34

2-( 2- hydroxy- 4- methoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

Prepared analogous example 28 from 2-hydroxy-4-methoxythiobenzoic acid morpholide methiodide (melting point: 180-181°C) and 2,3-diaminopyridine.

Melting point: 190-192°C (dec.).

Melting point of the free base: 292-293°C.

Example 35 2-(2',4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride Prepared analogously to example 28 from 2,4-dimethoxy-thiobenzpeic acid morpholide-meth iodide (melting point: 138- 140°C (dec.)j and 2,3-diaminopyridine Melting point: 238°C (from: methanol).

Example 36 2-(2,4-dimethoxy-phenyl)-6-methyl-1H-imidazo[4,5-b3pyridine-hydrogen chloride

Prepared analogously to Example 35 from 2,3-diamino-5-methyl- ... pyridine and 2,4-dimethoxy-thiobenzpeic acid morpholide methiodide. Melting point: 260-261°C.

Example 37 2-(2,4-dimethoxy-phenyl)-7-methyl-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogously to Example 35 from 2,3-diamino-4-methyl-pyridine and 2,4-dimethoxy-thiobenzpeic acid morpholide methiodide. Melting point: 230-231°C.

Example 38 2-(2,4-dimethoxy-phenyl)-5-methyl-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogously to Example 35 from 2,3-diamino-6-methyl-pyridine and 2,4-dimethoxy-thiobenzpeic acid morpholide methiodide. Melting point: 245-246°C.

Example 39 2-(2,4-dimethoxy-phenyl)-6-/chlor-1H-imidazo [4,5-b Ipyridine hydrogen chloride

Prepared analogously to Example 35 from 2,3-diamino-5-chloro-

pyridine and 2,4-dimethoxythiobenzpeic acid morpholide methiodide. Melting point: 253-255°C.

Example 40

2- ( 2- ethoxy- 4- methoxy- phenyl) - 1H-' imidazo[ 4, 5-b] pyridine- hydrogen chloride

Prepared analogously to Example 28 from 2-ethoxy-4-methoxythiobenzoic acid morpholide methiodide (melting point: 152-154°c) and 2,3-diamino-pyridine.

Melting point: 228-230°C.

Example 41

2-(2- methoxy- 4- ethoxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

Prepared analogous example 28 from 2-methoxy-4-ethoxy-thiobenzoic acid immorpholide methiodide and 2,3-diaminopyridine.

Melting point: 224-225°C (from methanol).

Example 42

2-( 2, 4- diethoxy- phenyl)- 1H- imidazo[ 4, 5- bJpyridine- hydrogen chloride

Prepared analogously to Example 28 from 2,4-diethoxy-thiobenzoic acid morpholide methiodide and 2,3-diaminopyridine.

Melting point: 224-226°C.

Example 43

2-[ 2-(2- hydroxy-ethoxy)-4- methoxy-phenyl]- 1H- imidazo! 4, 5-b]-pyridine hydrogen chloride

Prepared analogous example 28 from 2-(2-hydroxyethoxy)-4-methoxythiobenzoic acid morpholide methiodide and 2,3-diaminopyridine. Melting point: 237-239°C.

Example 44

2-[ 2-( 3- hydroxy- propoxy)- 4- methoxy- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine hydrogen chloride

Prepared analogous example 28 from 2-(3-hydroxy-propoxy)-4-methoxy-thiobenzoic acid morpholide methiodide and 2,3-diamino-pyridine. Melting point: 170°C (sintering).

Example 45

2- C2-( 2- methoxy- ethoxy)- 4- methoxy- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

Prepared analogous Example 28 from 2-(2-methoxyethoxy)-4-methoxythiobenzoic acid morpholide methiodide and 2,3-diaminopyridine. Melting point: 191-193°C.

Example 46

2-[ 2- methoxy- 4-( 2- methylmercapto- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

a) 4-(2-methylmercaptoethoxy)-2-hydroxybenzaldehyde

12 g of 2,4-dihydroxybenzaldehyde and 9.6 g of potassium tert.-butylate

was dissolved in 50 ml of ethylene glycol monomethyl ether, 9.6 g of methylmercaptoethyl chloride was added and the reaction mixture was stirred for 8 hours at 80°C (bath temperature). After removal of the solvent, the residue was taken up in dilute sodium hydroxide solution, the mixture was extracted twice with chloroform, the aqueous alkaline solution was separated

from:, acidified, extracted with chloroform, dried and concentrated. The residue was purified by means of column chromatography (silica gel). The oil obtained was used without further purification.

b) 4-(2-methylmercapto-ethoxy)-2-methoxy-benzaldehyde 9.7 g 4-(2-methylmercapto-ethoxy)-2-hydroxy-benzaldehyde

was dissolved in ethanol together with 6.7 g of potassium tert-butylate, 4.3 ml of dimethylsulphate was added and heated for 3 hours under reflux.

A further 1 ml of dimethylsulphate was then added and heated

for 1 hour. After distilling off the ethanol, the residue was taken up in water/chloroform, 2N caustic soda was added, the chloroform phase was separated, washed with water, dried and concentrated.

Melting point: 99-100°C (from cyclohexane). c) 4-{2-methylmercapto-ethoxy)-2-methoxy-thiobenzoic acid morphoride Prepared analogously to example 28a from 4-(2-methylmercapto-ethoxy)-2-methoxy-benzaldehyde. Melting point: 131-132°C (from ethanol). I d) 2-[2-Methoxy-4-(2-methylimercaptO-ethdoxy)-phenyl3-1H-imidazo[4,5-b]-. pyridine hydrogen chloride, -: 5»; 4 g of 4-(2-methylmercapto-ethoxy)-2-methoxy-thiobenzpeic acid morpholide: heat together with 1.2 ml. methyl iodide in 50 ml of acetone for 1.5 hours under reflux. After cooling, the solvent is removed and the resulting syrupy metiodide is heated with 3.6 g of 2,3-diaminopyridine in 20 ml of glycol for 1.5 hours at 120°C. dilute with water and shake with chloroform. 2N hydrochloric acid is then added to the organic phase, the yellow precipitate that falls out is sucked off. ■ Melting point: 197-199°C (from methanol) .. / f . Example 47 - •' 2- [ 2- methoxy- 4- ( 2- ethylmercaptoret6xy).- phenyl ]- 1H- imidazo[ 4, 5- b]- pyridine-hydrogehchloride ....

Prepared analogous example 46 from 4-(2-ethylmercapto-ethoxy)-2-methoxy-thiobenzpesvre-morpholide and•2,3-diaminopyridine.. End- . the products are purified by means of chromatography on silica gel and the precipitation of the hydrogen chloride by dissolving the base in acetone and adding an excess of ether/hydrochloric acid. methylmercaptopropoxy)-phenyl]-1H- imidazo [4,5-rb]-pyridine hydrogen chloride

Prepared analogous example 46 from 4-(3-methylmercaptopropoxy)-2-methoxythiobenzoic acid morpholide and 2,3-diaminopyridine. Melting point: 189-191°C (decomposition).

Example 49 2-[2-methoxy-4-(3-ethylmercaptopropoxy)-phenyl]-1H-imidazo[4,5-b 3-pyridine hydrogen chloride

Prepared analogous Example 46 from 4-(3-ethylmercaptopropoxy)-2-methoxythiobenzoic acid morpholide and 2,3-diaminopyridine. Melting point: 183-185°C (decomposition).

example 50 2-[ 2-( 2- methylmercapto- ethoxy)- 4- methoxy- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine hydrogen chloride

Prepared analogous Example 46 from 2-(2-methylmercaptoethoxy)-4-methoxythiobenzoic acid morpholide and 2,3-diaminopyridine. Melting point: 204-206°C (decomposition).

Example 51

2-[ 2-( 2- ethyl mercapto- ethoxy)- 4- methoxy- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

Prepared analogous example 46 from 2-(2-ethylmercaptoethoxy)-4-methoxythiobenzoic acid morpholide and 2,3-diaminopyridine. Melting point: 193-195°C.

Example 52 2-[ 2-( 3-methylmercapto-propoxy)-4- methoxy-phenyl]- 1H^ imidazo[ 4, 5- b 3 ~ pyridine hydrogen chloride Prepared analogously to Example 46 from 2-^ (3-methylmercapto-propoxy )-4-Methoxythiobenzoic acid^morph olide and 2,3-diaminopyridine. Melting point: 191-193°C.

Example 53 2-[2-(3-Ethylmercaptopropoxy)-4-methoxy-phenyl]-1H-imidazo[4,5-b3-pyridine hydrogen chloride

Prepared analogous example 46 from 2-(3-ethylmercapto-propoxy)-4-methoxythiobenzoic acid morpholide and 2,3-diaminopyridine. Melting point: 187-189°C.

Example 54

2-( 2, 3, 4- trimethoxy- phenyl)- 1H- imidazo[ 4, 5- b]- pyridine- hydrogen chloride

Prepared analogous example 28 from 2,3,4-trimethoxy-thiobenzoic acid -> morpholide methiodide (melting point: 147-150°C) and 2,3-diaminopyridine.

Melting point: 231-233°C (decomposition).

Example 55

2-( 2- methoxy- 3, 4- methylenedioxy- phenyl)- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogous example 28 from 2-methoxy-3,4-methylenedioxy-thiobenzoic acid morpholide methiodide (melting point: 109-11°C)

and 2,3-diaminopyridine.

Melting point: 266-268°C.

Example 56 2-(2,4-dimethoxy-3-hydroxy-phenyl)-1H-imidazo[4,5-b]pyridinium hydrogen chloride

Prepared analogous example 28 from 2,4-dimethoxy-3-hydroxy-thiobenzoic acid morpholide methiodide and 2,3-diaminopyridine. Melting point: 115-118°C.

Example 57

2-(2-Methoxy-4-chloro-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride Prepared analogously to Example 28 from 2-methoxy-4-chloro-thiobenz<p>acetic acid morpholide methiodide and 2,3-diaminopyridine.

Melting point: 302-305°C. ;

Example 58

2-(2-Methoxy-4-methyl-phenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

Prepared analogously to Example 28 from 2-methoxy-4-methyl-thiobenzoic acid morpholide methiodide and 2,3-diaminopyridine. Melting point: 256°C (decomposition).

Example 59

2-(2-ethoxy-4-methyl-phenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

Prepared analogously to Example 28 from 2-ethoxy-4-methyl-thiobenzoic acid morpholide methiodide (melting point: 142-144°C) and 2,3-diaminopyridine.

Melting point: 224-225°C (decomposition).

Example 60 2-(2-Methoxy-4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogous example 25 from 2-hydroxy-4-methyl-mercapto-benzoic acid morpholide (melting point: 124-129°C) and 2,3-diaminopyridine.

Melting point: 2 32-234°C.

Example 61

2-(2-Methoxy-5-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogously to Example 25 from 2-methoxy-5-methylmercapto-benzoic acid morpholide (melting point: 106-108°C) and 2,3-diaminopyridine. Melting point: 247-248°C.

Example 62

2-( 2- methoxy- 4- ethyl mercapto- phenyl)- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogously to Example 25 from 2-methoxy-4-ethylmercapto-benzbesyrmerfolide and 2,3-diaminopyridine.

Melting point: 215-217°C.

Example 63.

2-(2-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

Prepared analogously to Example 28 from 2-methylmercaptothiobenzoic acid morpholide methiodide and 2,3-diaminopyridine.

Melting point: 185-187°C.

Example 64 2-(2,4-bismethylmercaptophenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogously to Example 28 from 2,4-bismethylmercaptothiobenzoic acid morpholide met iodide and 2,3-diaminopyridine.

Melting point: 249-250°C.

Example 65

2-[ 2-( 2- methylmercapto- ethoxy)- 4- methylmercapto- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

Prepared analogous example 28 from 2-(2-methylmercapto-ethoxy)-4-methylmercapto-thiobenzoic acid morpholide methiodide and 2,3-diamino-pyridine.

Melting point: 180-182°C.

Example 66

2-[ 2-(2-diethylamino-ethoxy)-4-methylphenyl]-1H-imidazo[4,5-b]pyridine-dihydroqene chloride Prepared analogously to Example 28 from 2-(2-diethylamino-ethoxy)-4-methyl- thiobenzpeic acid morpholide metbdid hydrochloride and 2,3-diamino-

pyridine.

Melting point: 221-223°C.

Example 67 2-(2-allyloxy-4-methoxyphenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

16.5 g of 2-allyloxy-4-methoxy-benzoic acid morpholide and 7.1 g of 2,3-diaminopyridine are mixed well and pulverized and 30 ml of phosphorus oxychloride are added dropwise while stirring. The reaction mixture is then heated for 3 hours under reflux, then phosphorus oxychloride is removed bg the residue is decomposed with ice water. The solution which has been made alkaline with ammonia is extracted with chloroform, the organic solution is shaken with 2N hydrochloric acid, made alkaline again with ammonia, extracted again with /chloroform, the chloroform solution is dried, treated with activated charcoal/tbnsil, filtered and concentrated. The residue is dissolved in acetone and pale yellow hydrogen chloride precipitates. with ether/hydrochloric acid.

Melting point: 189-191°C.

Example 68 2-(2,4,5-trimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

a) 2-(2,4,5-trimethoxy-phenyl)-1,3-dithiolanium iodide

50 g of 1,2,4-trimethoxybenzene and 150 g of 2-methylmercapto-1,3-dithiolanium methsulfate are stirred in 600 ml of glacial acetic acid for 4 hours at a bath temperature of 70°C. The solvent is then removed, the residue is dissolved in a mixture of chloroform and water, an excess of potassium iodide solution is added to the aqueous phase, because the product separates out as orange-coloured crystals, which are used without further purification.

b) 2-(2,4,5-trimethoxyphenyl)^1H-imidazo[4,5-b]pyridine hydrogen chloride 3.8 g 2-(2,4,5-trimethoxy-phenyl)-1,3-dithiolanium -iodide and

2.2 g of 2,3-diaminopyridine is heated in 40 ml of glycol for 10 minutes at 200°C. After cooling, extract with ether and then with chloroform. The chloroform phase is shaken with 2N hydrochloric acid, the yellow hydrogen chloride that has precipitated is sucked off and recrystallized from glycol. Melting point: 278-280°C.

Example 69 2-(2,4,6-trimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

a) 2-(2,4,6-trimethoxy-phenyl)-1,3-dithiolanium iodide

33.6 g of phloroglucintrimethylether and 105 g of 2-methylmercapto-1,3-dithiolanium methsulfate are kept at 75°C in 200 ml of glacial acetic acid for 6 hours and the crystals that have precipitated after standing overnight are suctioned off, dissolved in water and the iodide combined out with potassium iodide solution.

Melting point: 153-154°C.

b) 2-(2,4,6-trimethoxy-phenyl)-1H-imidazb[4,5-b3pyridine hydrogen chloride 4 g 2-(2,4,6-trimethoxy-phenyl)-1,3-dithiolanium iodide ,

2.2 g of 2,3-rdiaminopyridine and 5 g of lead acetate are heated in 75 ml of glycol for 10 minutes, then the precipitated lead salt is filtered off, the filtrate is diluted with water and the precipitated product is sucked off.

After dissolution in methanol/hydrochloric acid, the product is purified over a silica gel column (eluent: chloroform:methanol = 9:1). Melting point: 241-244°C (from ethanol).

Example 70

2-(2,4-dihydroxy-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogous example 69 from 3-hydroxy-4-[1<*>,3'-dithia-cyclopentylidene-(2')]-cyclohexadiene-(2,5)-one-(1) and 2,3-diaminopyridine.

Melting point: 298-301°C.

Example 71

2-(4-dimethylamino-phenyl)-1H-imidazo[4,5- b 3pyridine- hydrogen chloride

"Prepared analogous example 69 from 2-(4-dimethylamino-phenyl)-1,3-dithiolanium iodide and 2,3-diaminopyridine in n-propanol. Melting point: 337-339°C.

Example 72

2-( 2- methoxy- 4- dimethylamino- phenyl)- 1H- imidazo[ 4, 5- b3pyridine hydrogen chloride

a) 2-(2- methoxy- 4- dimethylamino- phenyl)- 1, 3- dithiolanium- iodide

22.6 g of 3-dimethylamine<p>anisole, 43.2 g of 2-methylmercapto-1,3-dithiolanium methsulfate, 150 ml of glacial acetic acid and 22.5 ml of pyridine are heated for 1 hour under reflux. After cooling, it is poured into an aqueous potassium iodide solution, the precipitated product is sucked off and dried. Melting point: 18?-195°C (from dimethylformamide).

b) 2-(2-Methoxy-4-dimethylamino-phenyl)-1H-imidazo[4,5-b3pyridine hydrogen chloride

Prepared analogous example 42 from 2-(2-methoxy-4-dimethylamino.phenyl)-1,3-dithiolanium iodide and 2,3-diaminopyridine., . Melting point: 258-260°C (from methanol).

Example 73 2-(2-methylsulfinyl-phenyl)-1H-imidazo[4-,5-b]pyridine hydrogen chloride

Dissolve 1.35 g of 2-(2-methylmercapto-phenyl)-1H-imidaz6[4,5-b]pyridine in 20 ml of glacial acetic acid and add dropwise 0.64 g of 30% hydrogen peroxide dissolved in 5 ml of glacial acetic acid. After standing overnight, dilute with water, neutralize with sodium bicarbonate and the precipitated . product is sucked off and dried. By adding ether/hydrochloric acid to a methanol solution of the compound, the colorless hydrogen chloride is obtained.

Melting point: 205-21Q°C.

Example 74 2-(2-methylsulfonyl-phenyl)-1H-imidazo[4,5-bjpyridine hydrogen chloride

450 mg of 2-(2-methylmercapto-phenyl)-1H-imidazot4,5-b]pyridine hydrogen chloride and 370 mg of 30% hydrogen peroxide are heated in 20 ml of glacial acetic acid. for 3 hours at 70°C. After concentration and trituration with petroleum ether, the desired product crystallizes out.

Melting point: 259-262°C (from isopropanol):

Example 75 2-[2-(2-methylsulfinyl-ethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride

a) 2-[2-(2-methylmercaptoethoxy)-phenyl]-1H-imidazo [. 4, 5- b ] pyridine hydrogen chloride

Prepared analogously to Example 28 from 2-(2-methylmercaptoethoxy)thiobenzoic acid morpholide methiodide and 2,3-diaminopyridine. Melting point: 138-140°C.

b) 2-[2-(2-methylsulfinyl-ethoxy)-phenyl]-1H-imidazo:r4y5rb3pyridih-hydrogen chloride

4.3 g of 2-[2-(2-methylmercapto-ethoxy)-phenyl]-1H-imidazo[4,5-b]-pyridine hydrogen chloride and 1.5 g of 30% hydrogen peroxide are stirred in

100 ml of glacial acetic acid in. 2 hours at room temperature and the whole thing is left to stand

hats off. It is then diluted with water, neutralized with bicarbonate and extracted with chloroform. The chloroform phase is concentrated,

the residue is taken up in acetone and the hydrogen chloride is precipitated with methanol/hydrochloric acid.

Melting point: 163-165°C.

Example 76 2-[2-(2-methylsulfinyl-ethoxy)-4-methoxy-phenyl]-1H-imidazo[4,5-b]-pyridine hydrochloride Prepared analogously to Example 75b from 2-[2-(2- methyl mercapto-ethoxy)-4-methoxy-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 231-232°C.

Example 77 2-[2r(2-ethylsulfinyl-ethoxy)-4-methoxy-phenyl]-1H-imidazo! 4, 5-b] pyridine

Prepared analogously to Example 75b from 2-[2-(2-ethylmercapto-"ethoxy)-4-methoxy-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 188-189°C.

" Example 78 yr ■■■<:i.;..'.-2-[ 2-( 3- methylsulfinyl- propoxy)- 4- methoxy- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine Prepared analogous example 75b from 2-[2-(3-methylmercapto-propoxy)-4-methoxy-phenyl J-1H-imidazo[4,5-b]pyridine hydrogen chloride.M.P.: 132-133°C.

Example 79 2-[2-(3-ethylsulfinyl-propoxy)-4-methoxy-phenyl]-1H-imidazo[4,5-b]-pyridine

Prepared analogous example 75b from 2-[2-(3-ethylmercapto-propoxy)-4-methoxy-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 126-127°C.

Example 80 2-(2-Methoxy-4-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

6.6 g of 2-(2-methoxy-4-methylmercapto-phenyl)-1H-imidazo[4,5-b]-. vpyridine is dissolved in 100 ml of chloroform and added dropwise at -15°C. to -20°C during 5 hours a solution of 2.96 g of 3-chloroperoxybenzoic acid in 600 ml of chloroform. It is then shaken with a diluted soda solution, the chloroform phase is dried and concentrated. - The residue is purified. over eh silica gel color (eluent: chloroform/methanol = 9:1). By adding ether/hydrochloric acid to a methanol solution of the base '" A', the yellow hydrogen chloride is obtained. ESm ke sel mt pe ep l unk 8t 1 : 154■ -1';. 55°C. •. ;'' ' ,. -.- - ./ - .'■' .'■^ "' :•:'■■"•

2 - (2-Methoxy-4-methylsulfonyl-phenyl)-1H-Imidazo[4,5-b]pyridine-r-

Prepared analogous Example 74 from 2-(2-methoxy-4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride.

Melting point: 240-242°C.

Example 82

2-( 2- methoxy- 4- ethylsulfinyl- phenyl)- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogous Example 80 from 2-(2-methoxy-4-ethylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine.

Melting point: 121-123°C.

Example 83 2-[2-(2-methylsulfinyl-ethoxy)-4-methylmercapto-phenyl]-1H-imidazo[4,5-b3-pyridine

Prepared analogous example 80 from 2-[2-(2-methylmercapto-ethoxy)-4-methylmercapto-phenyl]-1H-imidazo[4,5-b]pyridine and

1 equivalent of 3-chloroperbenzoic acid.

Melting point: 191-192°C (from acetone).

Example 84 2-[2-(2-methylsulfinyl-ethoxy)-4-methylsulfinyl-phenyl]-1H-imidazo[4,5-b]-pyridine

Prepared analogous Example 80 from 2-[2-(2-methylsulfinyl-ethoxy)-4-methylmercapto-phenyl]-1H-imidazo[4,5-b]pyridine and 1 equivalent of 3-chloroperbenzoic acid.

Melting point: 190-191°C.

Example 85

2-[ 2-( 2- methylsulfinyl- ethoxy)- 4- methyl- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

Prepared analogous example 75 b from 2-[2-(2-methylmercapto-ethoxy)-4-methyl-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 191-192°C (from acetone/ether).

Example 86

2-[ 2-( 2- methylsulfinyl- ethoxy)- 4- chlorophenyl]- 1H- imidazo[ 4, 5-b]-pyridine hydrogen chloride

Prepared analogous Example 75b from 2-[2-(2-methylmercaptoethoxy)-4-chloro-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 221-222°C (from acetone/ether).

Example 87

2-[ 2- methoxy- 4-( 2- methylsulfinyl- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine

Prepared analogous example 75b from 2-[2-methoxy-4-(2-methylmercapt-,ethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 204-205°C.

Example 88

2-[ 2- methoxy- 4-( 2- ethylsulfinyl- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine

Prepared analogous Example 75b from 2-[2-methoxy-4-(2-ethylmercaptoethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrochloride. Melting point: 217-219°C.

Example 89

2-[ 2- methoxy- 4-( 3- methylsulfinyl- propoxy)- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine

Prepared analogous example 75b from 2-[2-methoxy-4-(3-methylmercapto-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride.

Melting point: 179-180°C..

Example 90

2-[ 2- methoxy- 4-( 3- ethylsulfinyl- propoxy)- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

Prepared analogous Example 75b from 2-[2-methoxy-4-(3-ethylmercapto-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride.

Melting point: 167-168°C.

Example 91

2-(2-Methoxy-5-methylsulfinyl^phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogous example 80 from 2-(2-methoxy-5-:methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride.. - ' Melting point: 211-212°C.

Example 92

2-( 2- methoxy- 5- methylsulfonyl- phenyl)- 1H- imidazo[ 4, 5-b] pyridine

Prepared analogous Example 74 from 2-(2-methoxy-5-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrochloride. Melting point: 240-241°C.

Example 93

2-(2,4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine-oxide-(4)

1 g of 2-(2,4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine and 1.35 g of 3-chloroperbenzoic acid are stirred for 15 hours in 15 ml of glacial acetic acid at 60°C. Then , recrystallized from 2n acetic acid during addition

of activated carbon. Cleaning by boiling with acetone.

Melting point: 266-267°C.

Example 94

2-( 2, 4- dlmethoxy- phenyl)- 3- methyl- 3H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

3.5 g of 2-(2,4-dimethoxy-phenyl)-1H-imidazo!4,5-b]pyridine hydrogen chloride and 2.7 g of potassium tert.-butylate are added to 40 ml of dimethylformamide and 3 is added dropwise, 6 g of methyl iodide. The mixture is then stirred for a further 2 hours at room temperature, concentrated, the residue taken up in chloroform/water, the organic phase separated, dried and concentrated. The product is purified using column chromatography and then precipitated out of solution in acetone with ether/hydrochloric acid. Melting point: 196-197°C.

example 95

2-(2-Hydroxy-phenyl)-3-methyl-3H-imidazo[4,5-b]pyridine- hydrogen chloride

Prepared analogous Example 94 from 2-(2-hydroxy-phenyl)-1H-imidazo[4,5-b]pyridine and methyl iodide.

melting point: 215-216°C.

Example 96

2-( 2- hydroxy- 4- methoxy- phenyl)- 3-( 3- hydroxypropyl)- 3H- imidazo[ 4, 5- b i pyridine- hydrogen chloride

Prepared analogous Example 94 from 2-(2-hydroxy-4-methoxy-enyl)-1H-imidazo[4,5-b]pyridine and 3-bromopropanol.

b;;melting point: 154-155°C.

Example 97 2-(2,4-dimethoxy-phenyl)-3-benzyl-3H-imidazo[4,5-b]pyridine-Y ydrogen chloride

Prepared analogous Example 94 from 2-(2,4-dimethoxy-phenyl)-H-imidazo[4,5-b]pyridine and benzyl bromide.

J. Melting point: 148-150°C.

jj^ sample 98

2 ( 2, 4- dimethoxy- phenyl)- 3-( 2- diethylaminoethyl)- 3H- imidazo[ 4, 5-b]-pyridine dihydrogen chloride

Prepared analogously to Example 94 from 2-(2,4-dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine and 2-diethylaminoethyl chloride at 80°C. Melting point: 185°C.

1-J example 99 'jv-ht, ?-(2,4-dimethoxy-phenyl)-3-(3-dimethylaminopropyl)-3H-imidazo! 4, 5-b]-pyridinium dihydrogen chloride

Prepared analogous Example 94 from 2-(2,4-dimethoxyphenyl)-3,H-imidazo[4,5-b]pyridine. and. 3-dimethylaminopropyl bromide at 70°C. Melting point: 190-192°C (decomposition).

Example 100

2-(2-methoxy-4-benzyloxy-phenyl)-1H-imidazo! 4, 5-b3 pyridine

Prepared analogously to Example 10 from 2-methoxy-4-benzyloxy-r-benzoic acid morpholide and 2,3-diaminopyridine.

Melting point for the hydrochloride: 218-219°C (decomposition).

Example 101 2-(2,4-dimethoxy-phenyl)-3-butyl-3H-imidazo[4,5-b]pyridine

Prepared analogously to Example 10 from 2,4-dimethoxy-benzoic acid morpholide and 3-amino-2-butylamino-pyridine. Melting point of the hydrochloride: 218-219°C. Example 102 2-(2-Methoxy-4-hydroxy-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogously to Example 10 from 2-methoxy-4-hydroxy-benzoic acid morpholide and 2,3-diaminopyridine. Melting point of the hydrochloride: 2 30-231°C.

Example 103 2-(2-ethoxy-4-ethylmercapto-phenyl)-1H-imidazo! 4, 5-b] pyridine

Prepared analogously to Example 10 from 2-ethoxy-4-ethyl mercapto-benzoic acid morpholide and 2,3-diaminopyridine. Melting point of the hydrochloride: 198-199°C (decomposition).

Example 104

2-[ 4- methoxy- 2-( 3-( 4- methyl- 1- piperazinyl)- propoxy)- phenyl]- 1H- imidazo[ 4, 5- b3pyridine

Prepared analogously to Example 21 from 2-[4-methoxy-2-(3-chloro-propoxy)-phenyl]-1H-imidazp[4,5-b]pyridine and 1-methylpiperazine. Melting point of the trihydrochloride: 248°C (decomposition).

Example 105

2 -[ 4- methoxy- 2r-( 2- thiomorpholino- ethoxy)- phenyl]- 1H- imidazo[ 4, 5- b]-pyridine

Prepared analogous example 21 from 2-14-methoxy-2-(2-chloro-ethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and thiomorpholine. Melting point: 158-160°C.

Example 106

2-(2-fluoro-4-methoxy-phenyl)-1H-imidazo[4,5-b3pyridine

Prepared analogously to Example 1 from 2-fluoro-4-methoxy-benzoic acid and 2,3-diaminopyridine.

Melting point of the hydrochloride: 237-238°C (decomposition).

Example 107

2-(4-fluoro-2-methoxy-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogously to Example 1 from 4-fluoro-2-methoxy-benzoic acid and 2,3-diaminopyridine.

Melting point of the hydrochloride: 235-236°C (decomposition).

Example 108

2-( 2- hydroxy- 4- methoxy- phenyl)- 3- phenyl- 3H- Imidazo[ 4, 5- b3pyridine

4.9 g of 2-hydroxy-4-methoxy-benzanilide and 2.6 g of 2-chloro-3-aminopyridine are heated in 50 ml of phosphorus oxychloride for 1 hour under reflux. After phosphorus oxychloride has been distilled off, the residue is boiled for 45 minutes with 2N hydrochloric acid, neutralized with ammonia and the precipitated product is recrystallized from isopropanol.

Melting point: 201°C...

Example 109

2-( 2- hydroxy- 4- methoxy- phenyl)- 3-( 2- methoxy- phenyl)- 3H- imidazo[ 4,5-b]-pyridine

Prepared analogous example 108 from N-(2-methoxy-phenyl)-2-hydroxy-4-methoxy-benzamide and 2-chloro-3-amino-pyridine. Melting point: 197°C.

Example 110 2-(2-hydroxy-4-methoxy-phenyl)-3-(4-methoxy-phenyl)-3H-imidazo[4,5-b]-pyridine Prepared analogously to example 108 from N-(4-methoxy- phenyl)-2-hydroxy-4-methoxy-benzamide and 2-chloro-3-amino-pyridine. Melting point: 175°C.

Example 111

2-( 2- hydroxy- 4- methoxy- phenyl)- 3-( 2- phenylethyl)- 3H- imidazo[ 4, 5-b]-pyridine

Prepared analogous example 108 from N-(2-phenylethyl)-2-hydroxy-4-methoxy-benzamide and 2-chloro-3-amino-pyridine.

Melting point: 155°C.

Example 112

2-( 2, 4- dimethoxy- phenyl)- 3- phenyl- 3H- imidazo[ 4, 5-b] pyridine

Prepared from N-phenyl-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine by heating for 5 minutes with sodium hydride in dimethylformamide at 120°C.

Melting point: 138°C (from cyclohexane/isopropanol = 9/1).

Example 113

2-( 2, 4- dimethoxy- phenyl)- 3-( 2- methoxy- phenyl)- 3H- imidazo[ 4, 5-b]- pyridine

Prepared analogous Example 112 from N-(2-methoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.

Melting point: 156°C.

Example 114

2-( 2, 4- dimethoxy- phenyl)- 3-( 4- methoxy- phenyl)- 3H- imidazo[ 4, 5-b] pyridine

Prepared analogous Example 112 from N-(4-methoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.

Melting point: 163°C.

Example 115

2-( 2, 4- dimethoxy- phenyl)- 3-( 3, 4- dimethoxy- phenyl)- 3H- imidazo[ 4, 5-b]-pyridine

Prepared analogous Example 112 from N-(3,4-dimethoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.

•Melting point: 190°C.

Example' 116 .„

2-( 3, 4- dimethoxy- phenyl)- 3-( 4- methoxy- phenyl)- 3H- imidazo[ 4, 5-b] pyridine

Prepared from Nr(4-methoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine" analogous to Example 112 or by boiling in chlorobenzene.

Melting point: 181°C.

Example 117

2-( 2, 4- dimethoxy- phenyl)- 3-( 3- morpholino- 1- propyl)- 3H- imidazo[ 4,5-b]-pyridine

Prepared analogous Example 112 from N-(3-morpholino-1-propyl)-N<1-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.

Melting point: 207°C.

Example 118

2-(2,6-dimethoxyphenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

9.1 g of 2,6-dimethoxy-benzoic acid and 5.5 g of 2,3-diaminopyridine are heated in 100 ml of phosphorus oxychloride for 3 hours under reflux, then the phosphorus oxychloride is spun off and the residue is carefully decomposed with ice water. The solution obtained is filtered, neutralized with potassium carbonate and made alkaline with concentrated ammonia.

The resulting suspension is extracted 3 times with chloroform, the chloroform phase is dried over magnesium sulphate, filtered, the solvent is removed and the remaining residue is dissolved in 50 ml of methanol/hydrochloric acid, then 100 ml of isopropanol is added and kept at a low temperature overnight. The precipitate that has formed is sucked off and washed with ether.

Melting point: 250-254°C.

Example 119

2-(2-propoxy-4-methyl-phenyl)-1H-imidazo[4,5-b]pyridine- hydrogen chloride

Prepared analogous example 118 from 2-propoxy-4-methyl-benzoic acid morpholide.

Melting point: 221-223°C (decomposition).

Example 120 2-(2-butoxy-4-methylphenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogous example 118 from 2-butoxy-4-methyl-benzoic acid morpholide.

Melting point: 211-213°C (decomposition).

Example 121 2-(4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogously to Example 118 from 4-methylmercapto-benzoic acid.

Melting point: 230-232°C.

Example 122

2-[ 2-( 2- methylmercapto- ethoxy)- 5- methylmercapto- phenyl]- 1H- imidazo[ 4, 5- b]- pyridine- hydrogen chloride 50 g S-methyl- [2-(2-methylmercapto- ethoxy) -5-methylmercapto]-thiobenzoic acid morpholide-iodide (obtained by reaction of [2-(2-methylmercapto-ethoxy)-5-methylmercapto]-thiobenzoic acid morpholide with methyl iodide in methanol) and 15 g of 2,3-diaminopyridine are heated in 150 ml of glycol for 3 hours at 130°C, after cooling dilute with water, add 30 ml of concentrated ammonia, extract with chloroform, wash the organic phase with water and then add 2N hydrochloric acid. The precipitate is suctioned off and recrystallized from methanol. Melting point: 190-191°C.

Example 12 3

2- ( 2- methoxy- 4- propyl mercapto- phenyl)- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogous Example 118 from 2-methoxy-4-propyl mercapto-benzoic acid morpholide.

Melting point: 203-204°C (decomposition).

Example 124

2-( 2- ethoxy~ 4- propyl mercapto- phenyl)- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogous Example 118 from 2-ethoxy-4-propylmercapto-benzoic acid morpholide.

Melting point: 182-183°C.

Example 125

2-(2-Methoxy-4-butylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogous Example 118 from 2-methoxy-4-butyl mercapto-benzoic acid morpholide.

Melting point: 203-204°C.

Example 126

2-( 2- ethoxy- 4- butylmercapto- phenyl)- 1H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogous Example 118 from 2-ethoxy-4-butyl mercapto-benzoic acid morpholide.

Melting point: 207-208°C.

Example 12 7

2-(4-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine 5.9 g of 2-(4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride is dissolved in 100 ml of glacial acetic acid and add 2.4 g of 30% hydrogen peroxide at 10°C. Then stir for 3 hours, let stand

overnight in an ice box and then 10 hours at room temperature, made alkaline with ammonia and extracted several times with chloroform. The starting material is separated using column chromatography, the residue is slurried in acetone and the formed crystallisate is sucked off..

Melting point: 240-242°C.

Example 128

2- ( 2- ethoxy- 5- methylsulfinyl- phenyl)- 1H- imidazo[ 4, 5- b3pyridine

Prepared analogous example 127 from 2-(2-ethoxy-5-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine.

Melting point: 197-198°C..

Example 129 2-[2-(2-methylsulfinyl-ethoxy)-5-methylmercapto-phenyl]-1H-imidazo-[4,5-b]pyridine

Prepared analogously to Example- 127. from 2-[2-(2-methylmercapto-ethoxy)-5-methylmercapto-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride.

Melting point: 189-190°C.

Example 130 2-(2-ethoxy-4-ethylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogous Example 127 from 2-(2-ethoxy-4-ethylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrochloride.

Melting point: 166-167°C.

Example 131 2-(2-Methoxy-4-propylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogous example 127 from 2-(2-methoxy-4-propylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 182-183°C.

Example 132

2-( 2- ethoxy- 4- propylsulfinyl- phenyl)- 1H- imidazo[ 4, 5-b] pyridine

Prepared analogous Example 127 from 2-(2-ethoxy-4-propylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrochloride. Melting point: 182-183°C (decomposition).

Example 133 2-(2-ethoxy-4-butylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogous Example 127 from 2-(2-ethoxy-4-butylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 185-186°C.

Example 134

2-( 4- methylsulfonyl- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

Dissolve 6.95 g of 2-(4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride in 100 ml of glacial acetic acid, add 8.5 g of 30% hydrogen peroxide and store for 4 days at room temperature.

After purification over a silica gel column, the residue is dissolved in acetone and the hydrogen chloride is combined with methanol/hydrochloric acid.

Melting point: 286°C.

Example 135

2-( 2- ethoxy- 4- ethylsulfonyl- phenyl)- 1H- imidazo[ 4, 5-b] pyridine

400 mg of 2-(2-ethoxy-4-ethylmercapto-phenyl)-1H-imidazo[4,5-b]-pyridine hydrogen chloride are dissolved together with 0.5 ml of 30% hydrogen peroxide in 30 ml of glacial acetic acid, then allowed to stand overnight over and then heated for 1 hour at 90°C, after cooling diluted with water, neutralized with bicarbonate, extracted with chloroform and after drying, the organic phase is concentrated and the residue is purified by means of column chromatography.

Melting point: 207-208°C (from acetone).

Example 136

2-(2-Methoxy-4-propylsulfonyl-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogous Example 135 from 2-(2-methoxy-4-propylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine.

Melting point: 219-220°C.

Example 137

2-( 2- ethoxy- 4- butylsulfonyl- phenyl)- 1H- imidazo[ 4, 5-b] pyridine

Prepared analogous Example 135 from 2-(2-ethoxy-4-butylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine.

Melting point: 156-157°C.

Example 138

2-[ 2- methoxy- 4-( 2- dimethylamino- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- dihydrogen chloride

a) 2-[2-Methoxy-4-(2-chloroethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride 14 g of 2-methoxy-4-(2-hydroxyethoxy)-benzoic acid morpholide is heated with 7.1 g of 2,3-diaminopyridine in 100 ml of phosphorus oxychloride for 1.5 hours under reflux. Ice water is then added, the precipitate, which gradually crystallizes, is sucked off and washed with acetone. Melting point: 266-268°C (decomposition).

b) 2 g of 2-[2-methoxy-4-(2-chloroethoxy)-phenyl]-1H-imidazo[4,5-b]-pyridine hydrogen chloride are heated with 5 g of dimethylamine in 100 ml

ethanol in a bomb for 12 hours at 120°C. After concentration, the residue is purified using column chromatography. The hydrogen chloride is precipitated from acetone with methanol/hydrochloric acid and then recrystallized from methanol.

Melting point: >250°C.

Example 139

2-[ 2- methoxy- 4-( 3- dimethylamino- propoxy)- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine dihydrogen chloride

Prepared analogous Example 138 from 2-[2-methoxy-4-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 238-242°C.

Example 140

2-[ 2- methoxy- 4-( 3- diethylamino- propoxy)- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine dihydrogen chloride

Prepared analogous Example 138 from 2-[2-methoxy-4-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 222-224°C.

Example 141

2-[ 2- methoxy- 4-( 3- piperidino- propoxy)- phenyl]- 1H- imidazo[ 4, 5-b]-pyridine dihydrogen chloride

Prepared analogous example 139 from 2-[2-methoxy-4-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 225-226°C (dec.).

Example 142

2-[ 2- methoxy- 4-( 3-( 4- phenyl- piperazin-l- yl)- propoxy)- phenylj- 1H- imidazo[ 4, 5-b] pyridine- dihydrogen chloride

Prepared analogous Example 139 from 2-[2-methoxy-4-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: 197-200°C.

Example 14 3

2-[ 2- methoxy- 4-( 3-( 4-( 2- methoxyphenyl)- piperazin- 1- yl)- propoxy)-phenyl]- 1H- imidazo[ 4, 5- b] pyridine- tri- hydrogen chloride- hydrate Prepared analogously to Example 139 from 2-[2-methoxy-4-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]pyridine hydrogen chloride. Melting point: sintering at 180°C.

Example 144

2-( 2- methoxy- 4- morpholino- phenyl)- 1H- imidazo[ 4, 5-b] pyridine- hydrogen chloride

a) 2-( 2- methoxy- 4- morpholino- phenyl)- 1, 3- dithiolanium- iodide

10.5 g of 3-morpholino-anisole and 15.7 g of 2-methylmercapto-1,3-dithiolanium metsulfate are boiled in a mixture of 60 ml of glacial acetic acid and 8.3 ml of pyridine for 1 hour and, after cooling, are poured into a saturated potassium iodide solution. The red precipitate is sucked off, washed with water and used without further purification.

b) 22 g of 2-(2-methoxy-4-morpholino-phenyl)-1,3-dithiolanium iodide, 10.9 g of 2,3-diaminopyridine and 60 ml of glycol are heated for 2 hours at

130°C, after cooling water is added and extracted with chloroform. After concentration, the residue is purified using column chromatography and the hydrogen chloride is precipitated from acetone with ether/hydrochloric acid.

Melting point: 207-209°c (decomposition).

Example 145

2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-1H-imidazo[4,5-b]-pyridine-dihydrogen chloride

Prepared analogous Example 144 from 3-(4-methyl-piperazin-1-yl)-anisole.

Melting point: 279-282°C.

Example 146

2-[2-Methoxy-4-(4-ethyl-piperazin-1-yl)-phenyl]-1H-imidazo[4,5-b]-pyridine dihydrogen chloride

Prepared analogous Example 144 from 3-(4-ethyl-piperazin-1-yl)-anisole.

Melting point: 218-222°C.

Example 147

2-[2-Methoxy-4-(4-propyl-piperazin-1-yl)-phenyl]-1H-imidazo[4,5-b]-pyridine dihydrogen chloride

Prepared analogous example 144 from 3-(4-propyl-piperazine-

1-yl)-anisole.

Melting point: 256-258°C.

Example 148 •

2-[ 2- ethoxy- 4-( 4- methyl- piperazin-l- yl)- phenyl]- 1H- imidazo[ 4, 5- b]- pyridine dihydrogen chloride

Prepared analogous Example 144 from 3-(4-methyl-piperazin-1-yl)-1-ethoxybenzene.

Melting point: 269-271°C.

Example 149

2- [ 2- ethoxy- 4-( 4- ethyl- piperazin-l- yl)- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- dihydrogen chloride

Prepared analogous Example 144 from 3-(4-ethyl-piperazin-1-yl)-1-ethoxybenzene.

Melting point: 25 7-25 9°C.

Example 150

2-[2-Methoxy-4-(4-phenyl-piperazin-1-yl)-phenyl]-1H-imidazo[4,5-b]-pyridine- dihydrogen chloride

Prepared analogous Example 144 from 3-(4-phenyl-piperazin-1-yl)-anisole.

Melting point: 217-219°C.

Example 151

2-[ 4- methoxy- 2-( 2- morpholino- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b] pyridine

Prepared from 6.3 g of 2-4-methoxy-2-(2-chloroethoxy)-phenyl-1H-imidazo[4,5-b]pyridine by refluxing for 3 hours in 60 ml of morpholine, distilling off the morpholine in vacuo and recrystallization from isopropanol.

Melting point: 188-190°C.

Example 152

2-[ 4- methoxy- 2-( 3-( 4- phenyl- piperazin- l- yl)- propoxy)- phenyl]- 1H- imidazo[ 4, 5-b] pyridine 10 g 2-[4- methoxy- 2-(3-chloropropoxy)-phenyl]-1H-imidazo-[4,5-b]pyridine, 10.2 g of 1-phenyl-piperazine and 5 g of potassium carbonate are heated for 8 hours in 100 ml of ethanol under reflux. After distillation of ethanol in vacuum, recrystallize from ethanol/water 3:1 Melting point: 162-163°C.

Example 153

2-[ 4- methoxy- 2- ( 3- ( 2- phenyl- ethylamino)- propoxy)- phenyl]- 1H-imidazo[ 4, 5-b] pyridine- dihydrogen chloride

Prepared by heating 1.77 g of 2-14-methoxy-2-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]pyridine in 10 ml of 2-phenyl-ethylamine at 180°C. The free base is transferred with methanol/hydrochloric acid into the dihydrogen chloride. Recrystallize from isopropanol. Melting point: 2 38°C.

Example 154

2-[ 4- methoxy- 2-( 3-( N- methyl- N- 2- phenylethyl- amino)- propoxy)- phenyl]-1H- imidazo[ 4, 5-b] pyridine- dihydrogen chloride

Prepared from 3.2 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and 2.7 g of N-methyl-2-phenylethylamine by heating for 6 hours in ethanol at 120°C in a bomb. Dihydrogen chloride is purified from an acetic ester solution using column chromatography, the free base is precipitated with ether/hydrochloric acid and recrystallized from isopropanol. Melting point: 212-215°C.

Example 155 2-[4-Methoxy-2-(3-(N-methyl-N-(2-(3,4-dimethoxyphenyl)-ethyl)-amino)-propoxy)-phenyl]-1H-imidazo [4, 5-b] pyridine dihydrogen chloride

Prepared-from 5.0 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and 8.5 g of N-[2-(3,4 -dimethoxyphenyl)-ethyl]-.methylamine by refluxing for 12 hours in ethylene glycol mono-. .methyl ether. ,Precipitation of dihydrogen chloride from acetic ester with ether/hydrochloric acid.

Melting point: 169°C.

Example 156 2-[4-methoxy-2-(3-thiomorpholino-propoxy)-phenyl]-1H-imidazo[4,5-b]-pyridine

Prepared analogous Example 155 from 2-[4-methoxy-2-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and thiomorpholine by heating for 30 hours. The purification is carried out by precipitating the malenate from acetic acid, and the base is liberated with 2n ammonia.

Melting point: 111°C.

Example 157

2-[ 4- methoxy- 2-( 2-( 4- methyl- piperazin- 1- yl)- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b] pyridine

Prepared from 3.0 g of 2-[4-methoxy-2-(2-chloroethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine..and 2.0 g of N-methylpiperazine by refluxing in 40 hours in ethanol. After column chromatography over silica gel, recrystallize from water.

Melting point: 136-137°C.

Example 158

2-[ 4- methoxy- 2- ( 3- ( 4-( 2- phenylethyl)-piperazin- 1- yl)- propoxy)-phenyl]- 1H- imidazo[ 4, 5- bJpyridine- trihydrogen chloride

Prepared analogous Example 154 from 2-[4-methoxy-2-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and 1-(2-phenyl-ethyl)-piperazine.

Melting point: 2 36-2 38°C.

Example 159

2-[ 4- methoxy- 2-( 3- methylamino- propoxy)- phenyl]- 1H- imidazo[ 4,5-b]- pyridine- hydrogen chloride

Prepared analogous Example 154 from 2-[4-methoxy-2-(3-chloro-propoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and methylamine. Melting point: 215°C.

Example 160

2-[ 4- methoxy- 2-( 2- dimethylamino- ethoxy)- phenyl]- 1H- imidazo[ 4, 5-b]- pyridine- dihydrogen chloride

Prepared analogous Example 154 from 2-[4-methoxy-2-(2-chloro-ethoxy)-phenyl]-1H-imidazo[4,5-b]pyridine and dimethylamine. Melting point: 2 40-242°C.

Example 161

2-(2-methylamino-phenyl)-1H-imidazo[4,5-b]pyridine

1.77 g of N-methyl isatoic anhydride and 1.09 g of 2,3-diamino-pyridine are fused together and heated for 10 minutes at 180°C. Recrystallized from acetic acid.

Melting point: 262-263°C.

Example 162

2-( 2, 4- dimethoxy- phenyl)- 3-( 2- phenyl- ethyl)- 3H- imidazo[ 4, 5-b] pyridine

0.17 g of 2-(2-hydroxy-4-methoxy-phenyl)-3-(2-phenyl-ethyl)-3H-imidazo[4,5-b]pyridine is dissolved in 7 ml of dimethylformamide. Stir for 5 minutes with 0.02 g of sodium hydride (80% suspension in oil) and react under ice-cooling with 0.07 g of methyl iodide. After 4 hours, water is added, the precipitated product is taken up in ethyl acetate, the organic phase is washed with 2N caustic soda and water and evaporated. Recrystallizes from ethanol/water.

Melting point: 157°C.

Example 16 3

2-( 2, 4- dimethoxy- phenyl)-3-[2-(3, 4- dimethoxy- phenyl)- ethyl]-3H- imidazo[ 4, 5-b] pyridine hydrogen chloride

Prepared analogous example 118 from 3-amino-2-[2-(3,4-dimethoxy-phenyl)-ethylamino]pyridine and 2,4-dimethoxy-benzoic acid. The hydrogen chloride precipitates out from ether.

Melting point: 195°C.

Example 164

2-(2-fluoro-5-methylmercapto-phenyl)-1H-imidazo[5,4-b]pyridine

Prepared analogous example 118 from 2,3-diamiropyridine and 2-fluoro-5-methylmercapto-benzoic acid. Melting point: 195°C.

Example 165

2-(2-fluoro-5-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared from 2-(2-fluoro-5-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine by oxidation with hydrogen peroxide in glacial acetic acid at room temperature, the purification is carried out by column chromatography on silica gel with chloroform/methanol 19: 1 as eluent.

Melting point: 190-192°C.

Example 166

2-( 2- fluoro- 5- methylsulfony 1- phenyl) - 1H- imidazo[ 4, 5-b] pyridine

Prepared from 2-(2-fluoro-5-methylmercapto-phenyl)-1H-imidazo-[4,5-b]pyridine as in Example 165, however at 40°C.

Melting point: 242°C.

Example 167 2-(3,4-dimethoxyphenyl)-3-(3-morpholino-propyl)-3H-imidazo[4,5-b]-pyridine dihydrogen chloride

a) N- ( 2-chloro- 3- pyridyl)- N'- ( 3- morpholinopropyl)- 3, 4- dimethoxy-benzamidine

4.9 g of N-(3-morpholinopropyl)-3,4-dimethoxy-benzamide and 2.04 g of 2-chloro-3-aminopyridine are heated in 85 ml of phosphorus oxychloride for 2 hours under reflux. After distilling off phosphorus oxychloride, it is poured into water, made alkaline and extracted with vinegar. After evaporation, the compound is obtained as a viscous oil.

b) 2-(3,4-dimethoxyphenyl)-3-(3-morpholino-propyl)-3H-imidazo[4,5-b]-pyridine dihydrogen chloride

5.2 g N-(2-chloro-3-pyridyl)-N'-(3-morpholiho-propyl)-3,4-

Dimethoxy-benzamidine and 1.5 g of sodium hydride (80% suspension in oil) are heated in 100 ml of dimethylformamide for 2 hours at 120°C. The dihydrogen chloride is precipitated from ether with hydrochloric acid and recrystallized from ethanol/cyclohexane.

Melting point: 180°C.

Example 168

2-(4-Methoxy-phenyl)-3-(3-morpholino-propyl)-3H-imidazo[4,5-b]-pyridine dihydrogen chloride

Prepared analogously to Example 16 7 from N-(2-chloro-3-pyridyl)-N'-(3-morpholino-propyl)-4-methoxy-benzmidine.

Melting point: 218°C.

Example 169

2- ( 4- methoxy- phenyl)- 3-[ 3- ( 4- phenyl- piperazin-1- yl)- propyl]- 3H- imidazo[ 4, 5-b] pyridine- dihydrogen chloride- hydrate

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N<1->[3-(4-phenyl-piperazin-1-yl)-propyl]-4-methoxy-benzmidine. Melting point: 100°C.

Example 170

2-( 4- methoxy- phenyl)- 3-( 2- morpholino- ethyl)- 3H- imidazo[ 4, 5-b]- pyridine- hydrogen chloride

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N'-(2-morpholino-ethyl)-4-methoxy-benzmidine.

Melting point: 149°C.

Example 171

2-( 4- methoxy- phenyl)- 3-[ 3-( 4- methyl- piperazin-l- yl)- propyl]- 3H-imidazo[ 4, 5-b] pyridine- trihydrogen chloride

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N'-[3-(4-methyl-piperazin-1-yl)-propyl]-4-methoxy-benzamidine.

Melting point: 257°C

Example 172

2-( 4- methoxy- phenyl)- 3-[ 2-( 4- methyl- piperazin- 1- yl)- ethyl]- 3H-imidazo[ 4, 5-b] pyridine- trihydrogen chloride

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N'-[2-(4-methyl-piperazin-1-yl)-ethyl]-4-methoxy-benzamidine.

Melting point: 225°C.

Example 173

2-( 4- methoxy- phenyl)- 3-( 3- dimethylamino- propyl)- 3H- imidazo[ 4, 5-b]-pyridine dihydrogen chloride

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N'-(3-dimethylamino-propyl)-4-methoxy-benzamidine.

Melting point: 229°C.

Example 174 2-(4-Methoxy-phenyl)-3-(3-piperidino-propyl)-3H-imidazo[4,5-b]-pyridine dihydrogen chloride

Prepared analogously to Example 16 7 from N-(2-chloro-3-pyridyl)-N'-(3-piperidino-propyl)-4-methoxy-benzamidine.

Melting point: 196°C.

. Example 175

2-( 4- methoxy- phenyl)- 3-( 4- morpholino- butyl)- 3H- imidazo[ 4, 5- b3pyridine dihydrogen chloride hydrate

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N'-(4-morpholino-butyl)-4-methoxy-benzamidine.

Melting point: 136°C.

Example 176

2-(2-Fluoro-4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine hydrogen chloride

Prepared analogous example 118 from 2-fluoro-4-methyl-mercapto-benzoic acid and 2,3-diaminopyridine.

Melting point: 257°C.

Example 177

2-(2-fluoro-4-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine

Prepared analogous example 165 from 2-(2-fluoro-4-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine. Crystallizes by trituration with petroleum ether.

Melting point: 219°C.

Example 178

2-( 4- methylmercapto- phenyl)- 3-( 3- morpholino- propyl)- 3H- imidazo[ 4, 5-b]-pyridine

Prepared analogous Example 167 from N-(2-chloro-3-pyridyl)-N'-(3-morpholino-propyl)-4-methylmercapto-benzamidine. Recrystallized from ether/cyclohexane.

Melting point: 110°C.

Example 179

2-[ 2- propoxy- 4-( 4- methyl- piperazin- l- yl)- phenyl]- 1H- Imidazo[ 4, 5- b]- pyridine- dihydrogen chloride ..Prepared analogously to example 144 from 3-(4- methyl-piperazin-1-yl)-1-propoxy-benzene.

Melting point: 237-238°C.

Claims (1)

Analogous process for the preparation of pharmacologically active imidazo[4,5-b]pyridines of the general formula I where means an alkylamino-, dialkylamino-, hydroxy-, allyloxy-, benzyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl, morpholino, N-phenylpiperazino or N-alkylpiperazino group, or an alkoxy group which may be substituted by a halogen atom, a hydroxy-, alkoxy-, alkylthio-, alkylsulfinyl-, alkylsulfonyl-, alkylamino-, dialkylamino-, piperidino-, morpholino-, thiomorpholino-, N-alkylpiperazino-, N-phenylpiperazino -N-methoxy-phenylpiperazino-, N-phenylethyl-piperazino-, phenylethylamino-, N-methyl-phenylethylamino- or N-methyl-dimethoxyphenyl-ethylamino group, 1*2 means a hydrogen or halogen atom, a methyl-, hydroxy-, Alkoxy-, alkylthio-, alkylsulfinyl or alkylsulfonyl group, R, means a hydrogen atom or an alkoxy group, or two of the radicals R^ to R^ together mean a methylenedioxy group, R^ means a hydrogen atom, one optionally with a hydroxy-, dialkylamino-, phenyl, dimethoxyphenyl, piperidino, morpholino, 4-methylpiperazino or 4-phenylpiperazino group substituted alkyl radical, or a phenyl radical optionally substituted with halogen atoms or methoxy groups, and R,, means a hydrogen or halogen atom or an alkyl radical, wherein the specified alkyl, alkylthio, alkoxy, alkylsulfinyl and alkylsulfonyl residues contain 1-4 carbon atoms, and physiologically compatible acid addition salts thereof with inorganic or organic acids, characterized in that a pyridine of the general formula II where R, - is as indicated above, and Y means a halogen atom or an R^NH group, where R^ is as indicated above, is reacted with a compound of the general formula III ■ where R^ to R^ are as indicated above, and X means a carboxyl group or a functional derivative thereof, and a thus obtained compound of the general formula I containing a reactive halogen atom is optionally transferred with an amine to the corresponding amino compound, and/or a thus obtained compound of the general formula I containing a reactive hydrogen atom is optionally alkylated in the presence of a base with an alkylating agent, and/or a thus obtained compound of the general formula I is optionally converted with an oxidizing agent into the corresponding N-oxide, S-oxide or S,S-dioxide compound, and/or its physiologically compatible acid addition salt is optionally transferred with an inorganic or organic acid"