FI91758B - Method for production of a 5-(6-imidazo[1,2- a]pyridyl)pyridine derivative which can be used as a medicinal product - Google Patents

Description

91758

The present invention relates to novel 5- (6-imidazo [1,2-a] pyridyl) pyridine derivatives having excellent cardiotonic activity. The present invention relates to novel 5- (6-imidazo [1,2-a] pyridyl) pyridine derivatives having excellent cardiotonic activity. . In particular, this invention relates to processes for the preparation of novel 5- (6-imidazo [1,2-a] pyridyl) pyridine derivatives and their pharmaceutically acceptable salts.

One light underlying cause of congestive heart failure is impaired myocardial contraction.

To date, digital products have been used to treat such heart failure. Digital products have been made for 200 years and have become almost synonymous with heart drugs. However, there are problems with digital products due to the low limits of both effective doses and toxic doses. In addition, their impact is also insufficient.

Cardiac drugs that affect the sympathetic nerves, such as isoprotenol, dopamine, dobutamine, etc., have also been widely used. However, not only do these cardiac drugs have side effects such as an increase in the number of heartbeats, a tendency to cause arrhythmias, etc., but their effect is effective only in intravenous drip injection. Thus, these cardiac drugs cannot be used to treat chronic heart failure.

Thus, attention is now focused on the development of cardiac drugs that can be administered orally and have appropriate duration of action; such heart medications are really desirable.

For example, German application 3406329 describes certain imidazo (1,2-, a) pyridine derivatives which affect the function of the heart.

The inventors of the present invention have studied compounds having a potent and long-acting cardiotonic effect in oral use for a long time, and have finally found that the following compounds can achieve the desired purpose and have thus accomplished the present invention.

The present invention relates to new compounds of general formula (I).

Yy> a; The imidazo [1,2-a] pyridinylpyridine derivatives according to claim 10, wherein R1 represents a hydrogen atom or a methyl group and W represents a methyl or ethyl group, and pharmaceutically acceptable salts of these compounds.

The invention is precisely defined in the claims.

The compounds according to our invention are more active than, for example, those known from DE 3406329.

20 R '/ ¾ of general formula (II).

YY>.: 25

B

The tautomers of the invention are obviously included within the scope of this invention. Tautomers may also be present as an equilibrium mixture.

The pharmacologically acceptable salt of the compound of this invention relates to a conventional non-toxic salt. Specific examples of such salts include alkali metal salts such as sodium salts, potassium salts, etc., underground potassium metal salts such as calcium salts, magnesium salts, etc., ammonium salts, organic base salts such as trimethylamine salts, picoline salts, pyridine salts, pyridine Ν, Ν'-dibenzylethylenediamine salts 5, etc., inorganic acid salts such as hydrochlorides, hydrobromides, sulfates, phosphates, etc., organic acid salts such as formates, acetates, trifluoroacetates, maleates, tartrates, sulfonates, methanesulfonates, methanesulfonates, methanesulfonates, salts formed with amino acids such as arginine salts, ornithine salts, etc.

In addition to the above-mentioned cardiotonic effect, the compounds of the present invention have properties such as a very minimized increase in heart rate, a dilating effect on blood vessels, a wide range of safety and an antiplatelet effect, etc.

Thus, it is an object of the present invention to provide novel compounds having an excellent cardiotonic effect.

It is also an object of the present invention to provide novel compounds which have an effective and long-lasting cardiotonic effect in oral use.

There are several methods for preparing the compounds of this invention. A few of these methods are presented below.

The compound of the present invention can be prepared, for example, by the following method ΥΠ

OH

B

• · t 4 91758 where the residues R1 and W have the meanings given above.

w / vNiY0H

10

Namely, the 1,2-dihydro-5- (imidazo [1,2-a] pyridin-6-yl) -2-oxo-3-pyridinecarbonitrile derivative of the general formula (II ') is heated at 80 to 200 ° C with mineral meat. -15 pon in aqueous solution to give compound (I).

Heating is best performed at 100 to 180 ° C for about 15 to 30 hours in an 80% aqueous solution of phosphoric acid or an 80% aqueous solution of sulfuric acid.

The compound of formula (II ') can be prepared as follows.

Method of manufacture 1

A compound of the following general formula (III) ·: 25, wherein R1 and W have the meanings given above, is reacted with the general formula (IV) ».

5 91758 8 '° ~ 8β r.> N-c-h (IV) with a compound of formula 0-8' 10 wherein R7 and R8 represent a lower alkyl group to give a general formula (V) r, ynv% T I i? nAAw δ (V) i

OF

/ \

R8 RT

A compound according to 20, wherein R1 and W have the meanings given above (first step).

The obtained compound (V) is then reacted with cyanoacetamide under basic conditions to give RV% of the general formula (II ').

w H

wherein R1 and W have the meanings given above 35 6 91 758 (second step).

The reaction of the first step is carried out at room temperature at -120 ° C in the presence or absence of solvents in a conventional manner. Examples of the solvent include acetonitrile, dimethylformamide, tetrahydrofuran, dioxane, benzene, hexamethylphosphoramide, ether, etc. When no solvent is used, the use of excess compound (IV) gives the best results.

The second step reaction can be performed by heating in solvents in the presence of basic condensing agents.

In particular, the best results are obtained by carrying out the reaction in solvents such as lower alcohols, e.g. methyl alcohol, ethyl alcohol, propyl alcohol, etc., dimethylformamide or hexamethylphosphoramide 15, etc., in the presence of bases such as alkali metal alkoxides, preferably sodium methoxide or sodium ethoxide. Specific examples of the best combinations of other solvents and bases include a combination of tetrahydrofuran used as a solvent, acetonitrile, dioxane, etc., and sodium hydride used as a base, lithium diethylamide, lithium diisopropylamide, etc.

Process for the preparation of the starting material In the process for the preparation of the compounds of the present invention, a compound of the general formula (III) which can be used as a starting material can be prepared, for example, by the following methods.

(Preparation Method 11 30 Method 1 ™? Is shown to illustrate, [first step] vn 91758 7 in which Hai represents a halogen atom and the residue R1 has the meaning given above, + 5 CH,

Ha ^ ~ CH, —i —W

10 wherein the residues Hai and W have the meanings given above.

f Grignard reaction i 20 (ιχ> where R1 and W have the meanings given above.

[second stage] * * l 6 91758 I Oxidation 5 i '

Vys ίο [I_I). o (m) 15 wherein the radicals R1 and W have the meanings given above.

Production Method 1 is described in more detail below.

First Step In this step, a compound of general formula (IX) is prepared by reacting a 6-haloimidazo [1,2-a] pyridine derivative of general formula (VII) with a β-alkylallyl halide of general formula (VII). In a conventional Grignard reaction, a compound of general formula (VII) is first reacted with magnesium in ether-type solvents such as diethyl ether, tetrahydrofuran, dibutyl ether, diglyme, etc., or in hydrocarbon-type solvents such as toluene, xylene. To form a Grignard reagent; then the Grignard reagent is reacted with β-α-10 alkyl allyl halide (III). The best example is given in particular in the following: A compound of general formula (VII) is added to 4 equivalents of magnesium in diethyl ether or tetrahydrofuran using 3 equivalents of ethyl bromide to form a Grignard reagent. A solution of 4 equivalents of β-alkylallyl halide in diethyl ether or tetrahydrofuran is then reacted with Grignard reagent to complete the reaction.

9 91758

The reaction is carried out at room temperature under reflux. Second step In this step, the compound (IX) obtained in the first step is oxidized to give a compound of general formula (III).

Examples of the oxidation include an oxidation process in which ozone is introduced into the reaction at a temperature below 10 ° C in a solvent mixture such as methanol-water, methanol-dilute hydrochloric acid, acetic acid-water, etc. or in solvents such as methanol, acetic acid, methylene chloride. in chloroform, etc., oxidation method by oxidation with osmium tetraoxide and periodate, osmium tetraoxide and hydrogen peroxide, etc. in solvents such as dioxane, pyridine, tetrahydrofuran, alcohols, etc.

One of the best methods is to lead the reaction to ozone n.

At 5 ° C in a solvent mixture such as methanol-dilute chloro-hydrochloric acid or acetic acid-water.

Production Method 2 (X) U 1; 25 wherein R 9 is hydrogen or a lower alkali group and the residue R 130 has the meaning given above.

[first step] • »5 10 91758

Reduction Ψ ΊΓΓχ -f 15

OjNCH, W (XE) wherein W represents a hydrogen atom or a lower alkyl group.

[second stage] 20. 25 V-

syVS

! l_i X NO, i \

H W

wherein the residue W has the meaning given above.

Γ · 5 [third stage] |] 91758 11

Reduction Hydrolysis 5 'r

R '^ fNV ^ l o («O

15 wherein R1 and W have the meanings given above.

Production Method 2 is described in more detail below.

First step In this step, a compound of general formula (X), which is a starting material prepared by a known method, is reduced to prepare a formyl compound of general formula (XI). The reaction is carried out at a reaction temperature below -40 ° C. In general, patients use lithium aluminum hydride, hydride, diisobutylaluminum hydride, etc. as the reducing agent and diethyl ether, tetrahydrofuran, dioxane, toluene, dichloroethane, etc. as the solvent.

Second Step In this step, a formyl compound of general formula (XI) is condensed with a nitroalkane (XII) to give a compound of general formula (XIII).

Nitroalkane (XII) means in particular a nitro-lower alkane such as nitromethane, nitroethane, nitropropane, nitrobutane, etc.

The condensation is generally carried out in the presence of, for example, alkylamines, ammonium acetate, β-alanine, etc. The third stage

In the reaction, the compound of general formula (XIII) is reduced and hydrolyzed to give the compound of general formula (III). The reaction is carried out in a conventional manner. As an example to obtain the best results, compound (XIII) is treated with concentrated hydrochloric acid under heating in an aqueous alcoholic solvent in the presence of iron or ferric chloride hydrate or treated with zinc-10 powdered powder in acetic acid.

From the formyl compounds of the general formula (XI) used as starting materials in the second step, compounds in which R2 is a hydrogen atom and R3 is a hydrogen atom, a lower alkyl group, a lower alkyl group or a fluorine atom can also be obtained by reacting the above compound (VII) with magnesium in ether type solvents. , such as diethyl ether, tetrahydrofuran, dibutyl ether, diglyme, etc., or hydrocarbon-type solvents such as toluene, xylene, tetralin, etc. to form Grignard reagents and then reacting the Grignard reagents with alkyl forms, N, N-dimethylform. or with magnesium bromide formate. These compounds are best prepared by adding Compound (VII) to an equimolar amount of magnesium in a diethyl ether or tetrahydrofuran solvent, forming a Grignard reagent using 3 equivalents of ethyl bromide, and reacting the Grignard reagent with N, N-dimethylformamide, an alkyl bromide formate, or magnesium bromide formate. with.

30

Test 1

Function of contracted guinea pig myocardium immediately after killing male guinea pigs weighing 300-500 g, the heart was isolated and the right ventricular muscle was removed to a nutrient solution containing a solution saturated with a gas mixture (95% O 2 and 5% CO 2) and suspended. Magnus tube.

• * • · 91758 13 Using Krebs-Henseleit solution as the nutrient solution, the solution was moistened at a rate of about 3 ml / min. The temperature of the Magnus tube was maintained at 36 ° C and the gas mixture was passed through the tube.

5 The right ventricular flesh was electrically stimulated under the following conditions: 1 Hz, 3 ms (stimulation time) and threshold x 120% (V). The reduction thus obtained was recorded on an FD recorder. The experiment was performed by applying such a load to the isolated right ventricular muscle to obtain maximum contraction. The test compound was dissolved in dilute hydrochloric acid medium and the resulting solution was placed in a Magnus tank. The contraction was compared after and before administration.

The test compound was later the compound shown in the example.

The results are shown in Table 1.

Table 1 2 0 _

Concentration Shrinkage (M) __ (A%) _ 10 "6 37.9 10" 5 76.3 25 10 ~ 4__110.1_ 30 Experiment 2

Cardiac shrinkage in an anesthetized dog Using male and female mixed-breed dogs given artificial respiration and ankle-strapped by inhalation with Halocene, cardiotonic activity was examined. Millar) fitted to the left ventricle of the carotid artery. 5 saline or dilute hydrochloric acid or polyethylene glycol and the solutions were administered intravenously via a catheter inserted into the femoral vein.

Table 2 shows the rates of change of the test compound in the increase of myocardial contraction, the number of heartbeats in this case and the blood pressure obtained by the previous method compared to the values obtained before the administration of the test compounds. In Table 2, the test compound is the compound prepared in the example later.

15 Table 2

Dose Heart Cardiac Blood (Mg / kg) change in muscle stroke pressure change change%% __% ___ 10 11 2 -2 20 30__25__4_ -5 |

Experiments show that the compounds of this invention have excellent cardiotonic activity.

25

Acute toxicity test

Acute toxicity was tested in oral use using rats and mice. The results show that the compounds of this invention have very low toxicity.

Thus, the compounds of this invention are characterized by excellent cardiotonic activity, very low toxicity and are very safe. Very low toxicity is very important in view of the fact that drugs or cardiotonic agents for the treatment of heart failure must be administered continuously for long periods of time, and thus this invention is very valuable.

Furthermore, in an experiment in which the compounds of this invention were administered orally to normal dogs, an improvement in heart contraction was observed without greatly affecting the heart rate and this effect was long-lasting. This long-lasting cardiotonic effect is also very important in drugs for the treatment of heart failure and in cardiotonic agents.

From the above, it can be said that the compounds of the present invention are excellent drugs for the treatment of heart failure and are very safe and long-acting.

The compounds of this invention are very useful, in particular for the treatment of the following diseases.

That is, the compounds are useful in the treatment of chronic congestive heart failure involving old myocardial infarction, inflammation of the heart valves, dilation myocardiosis, hypertension, etc.

When the compound of the present invention is administered to patients suffering from the above-mentioned diseases for the treatment of heart failure, its dose is not particularly limited because it varies depending on the nature of the disease, the condition, the compound, the age of the patient, etc .; however, combined ·. The tea is generally administered orally or parenterally to an adult in a daily dose of about 10 to 1000 mg, preferably about 10 to 100 mg, 1 to 4 times a day.

Exemplary compounds are set forth below without limiting the invention thereto.

Preparation of starting material a) 1- (Imidazo [1,2-a] pyridin-6-yl) -2-propanone: (1) 24.5 g of magnesium placed in a 4-necked 2-liter flask , a solution of 8.25 g of ethyl bromide in 14 ml of tetrahydrofuran is added dropwise under a stream of nitrogen. After the addition is complete, a solution of 49.25 g of 6-bromoimidazo [1,2-a] pyridine and 74.25 g of ethyl bromide in 300 ml of tetrahydrofuran is added to the mixture over a period of 40 minutes while maintaining an internal temperature of 50-60 ° C. After the addition is complete, the reaction mixture is stirred at reflux for 5 hours to form the Grignard reagent.

Next, the reaction mixture is cooled and a solution of 97.5 g of 2-chloromethyl-1-propene in 200 ml of tetrahydrofuran is added dropwise at an internal temperature of 0-10 ° C. After the addition is complete, the mixture is stirred at reflux for 2 to 10 hours. After cooling (30-40 ° C), a solution of 50 g of ammonium chloride in 500 ml of water is added dropwise to the reaction mixture. After cooling, 250 ml of toluene, 200 ml of n-hexane and 200 ml of water are added to the mixture. The organic layer is filtered. The organic layer is washed twice with brine and dried over magnesium sulfate. The solvent is removed by distillation under reduced pressure to give 30.5 g (70.9%) of 6- (2-methyl-2-propenyl) imidazo [1,2-a] pyridine, b.p. 118-122 ° C (0.5 mmHg).

Nuclear Magnetic Resonance Spectrum (CDCl 3) δ 7.94 (1H, m), 7.72 (1H, d, J = 1 Hz), 7.56 (1H, d, J = 9 Hz), 7.52 (1H, d, J = 1 Hz), 7.02 (1H, dd, J = 2.9 Hz), 4.90 (1H, d, J = 1 Hz), 4.80 (1H, d, J = 1 Hz) ), 3.28 (2H, s), 1.70 (3H, s).

25 (2) To a solution of 12.3 g of conc. hydrochloric acid,. 45 ml of water and 45 ml of methanol are dissolved in 20 g of 6-isobutenylimidazo [1,2-a] pyridine. The solution is cooled to -5 ° C. Ozone is introduced into the solution at -5-0 ° C for 4 hours. The completion of the reaction is confirmed by thin layer chromatography. After completion of the reaction, a solution of 30.6 g of sodium sulfite in 160 ml of water is added dropwise with cooling at such a rate that the temperature does not rise above 20 ° C. 22 g of sodium bicarbonate and the appropriate amount of salt are then added as solids and the mixture is extracted with chloroform. The chloroform extract is washed twice with saturated brine. After drying over magnesium sulfate, the chloroform is removed by distillation under reduced pressure to 91758 17. The residue is purified by distillation under reduced pressure to give 14.2 g (70.5%) of 1- (imidazo [1,2-a] pyridin-6-yl) -2-propanone, b.p. 155-159 ° C (0.4 mmHg).

Nuclear Magnetic Resonance Spectrum (CDCl 3): 8.03 (1H, m), 7.64 (1H, s), 7.60 (1H, d, J = 9 Hz), 7.56 (1H, s), 6, 95 (1H, dd, J = 2.9 Hz), 3.70 (2H, s), 2.24 (3H, s).

b) 1- (Imidazo [1,2-a] pyridin-6-yl) -2-propanone: 6.9 g of 6-imidazo [1,2-a] pyridinecarbaldehyde are stirred in 40 ml of ethanol. and 10.6 g of nitroethane and 30 drops of n-butylamine under reflux for 14 hours. A small amount of ethylamine is then added and the mixture is stirred at reflux for a further 18 hours. Insoluble materials are removed by filtration with heating, followed by the addition of 50 ml of ethanol and 150 ml of ether to remove insolubles by filtration. The solvent is removed by distillation under reduced pressure and the residue is recrystallized twice from ethanol to give 1.14 g of 6- (2-nitro-1-propenyl) imidazo [1,2-a] pyridine, m.p.

190-192 ° C (decomposed).

Nuclear Magnetic Resonance Spectrum (CDCl 3): 8.30 (1H, d, J = 2 Hz), 8.04 (1H, d, J = 1 Hz), 7.73 (1H, d, J = 1 Hz), 7, 70 (1H, d, J = 9 Hz), 7.66 (1H, d, J = 1 Hz), 7.26 (1H, dd, J = 2.9 Hz), 2.52 (3H, · d, J = 1 Hz).

(2) In 25 ml of water and 25 ml of EtOH, 1.14 g of 6- (2-nitro-1-propenyl) imidazo [1,2-a] pyridine and 100 mg of ferric chloride are heated to 80 ° C. With stirring, add 2.5 ml of 30 conc. hydrochloric acid at reflux and the mixture is stirred for one hour. Upon heating, insolubles are removed by filtration. The insolubles are washed thoroughly with ethanol, after which the solvent is removed by distillation under reduced pressure. Aqueous sodium bi-35 carbonate solutions are added to the residue, and the mixture is extracted with chloroform. Wash with water and dry over magnesium sulfate, then remove the chloroform by distillation under reduced pressure. The residue is purified by column chromatography to give 500 mg of 1- (imidazo [1,2-a] pyridin-6-yl) -2-propanone.

The nuclear magnetic resonance spectrum is identical to that shown in 5a.

c) The reaction is carried out in the same manner as in a. The corresponding derivatives given below are obtained.

1- (imidazo [1,2-a] pyridin-2-yl) -2-butanone: nuclear magnetic resonance spectrum (CDCl 3): δ 7.98 (1H, d, J = 2 Hz), 7.56 (1H, s ), 7.53 (1H, d, J = 9 Hz), 7.50 (1H, s), 6.94 (1H, dd, J = 2.9 Hz), 3.64 (2H, s). , 2.52 (2H, q, J = 7Hz), 1.06 (3H, t, J = 7Hz). 1- (methylimidazo [1,2-a] pyridin-2-yl) -2-butanone: nuclear magnetic resonance spectrum (CDCl 3): δ 7.76 (1H, m), 7.30 (1H, d, J = 9 Hz), 7.12 (1H, s), 6.76 (1H, dd, J <2.9 Hz), 3.48 (2H, s), 2.40 (2H, q, J = 7 Hz) , 2.30 (3H, S), 0.94 (3H, t, J = 7Hz).

1- (5-methylimidazo [1,2-a] pyridin-2-yl) -2-propanone: melting point: 70-73 ° C

Nuclear Magnetic Resonance Spectrum (CDCl 3): 7.61 (1H, d, J = 1 Hz), 7.46 (1H, d, J = 10 Hz), 7.42 (1H, d, J = 1 Hz), δ , 92 (1H, d, J = 10 Hz), 3.92 (1H, d, J = 10 Hz), 3.71 (2H, s), 2.44 (3H, s).

2.12 (3 H, S).

25 *: Preparation of 1,2-dihydro-5- (imidazo [1,2-a] pyridin-6-yl) -6-methyl-2-oxo-3-pyridinecarbonitrile in 230 ml of Ν, Ν-dimethylformamide is dissolved 23.5 g of 4-30 dimethylamino-3- (imidazo [1,2-a] pyridin-6-yl) -3-buten-2-one. The solution is stirred at 80-90 ° C for 12 hours together with α-cyanoacetamide (9.48 g) and sodium methoxide (12.2 g). After cooling, the solvent is removed by distillation under reduced pressure, and 500 ml of water are added to dissolve the residue. The solution is washed with 600 ml of chloroform.

About 5 ml of acetic acid is then added to the aqueous layer to adjust the pH to 6.5. Precipitated on cooling • »

II

91758 19 crystals are collected by filtration. The crystals are washed with water, acetonitrile and then ether, after which they are dissolved in 200 ml of 2.5% aqueous sodium hydroxide solution. The solution is treated with activated carbon. The filtrate 5 is again adjusted to pH 6.5 with about 7 ml of acetic acid.

Upon cooling, the precipitated crystals are collected by filtration. The crystals are washed with water, acetonitrile and then ether, after which they are recrystallized from 100 ml of N, N-dimethylformamide to give 13 g of 1,2-dihydro-6-methyl-2-oxo-5- (imidazo [ 1,2-a] pyridin-6-yl) -3-pyridinecarbonitrile, m.p. 300 ° C or higher.

(value, ppm, TMS international standard, DMSO-d6). Nuclear Magnetic Resonance Spectrum (DMSO-D6): 12.77 (b, s), 8.58 (1H, m), 8.15 (1H, S), 7.92 (1H, s), 7.61 (1H) , S), 7.60 (1H, d, J = 9 Hz), 7.22 (1H, dd, J = 9.2 Hz), 2.29 (3H, s)

The following compounds are obtained as shown.

1,2-Dihydro-6-ethyl-5- (2-methylimidazo [1,2-a] pyridin-6-yl) -2-oxo-3-pyridinecarbonitrile: melting point: 274-278 ° C (dispersed) nuclear magnetic resonance spectrum (DMSO-d 6): 12.68 (b, s), 8.44 (1H, m), 8.10 (1H, s), 7.65 (1H, s), 7.45 (1H, d) , J = 9 Hz), 7.08 (1H, dd, J = 2.9 Hz), 2.52 (2H, q, J = 7 Hz), 2.33 (3H, s), 1.09 (3H, t, J = 7 Hz) 1,2-Dihydro-6-ethyl-5- (imidazo [1,2-a] pyridin-6-yl) -2-oxo-3-pyridinecarbonitrile: melting point: 250- 252 ° C (dispersed) nuclear magnetic resonance spectrum (DMSO-d 6): JO 12.72 (b, s), 8.58 (1H, m), 8.12 (1H, s), 7.96 (1H, s) , 7.64 (1H, S), 7.63 (1H, d, J = 9 Hz), 7.20 (1H, dd, J = 2.9 Hz), 2.49 (2H, q, J = 7 Hz), 1.10 (3H, t, J = 7 Hz).

Example 35 1,2-Dihydro-6-methyl-5- (imidazo (1,2-a] pyridin-6-yl) -2-oxopyridine: 10 ml of 85% phosphoric acid is heated to reflux. under cooling with 1 g of, 2-dihydro-6-methyl-5- (imidazo [1,2-a] pyridin-6-yl) -2-oxo-3-pyridinecarbonitrile for 18 hours, after cooling, water is added and then the mixture is extracted with chloroform, washed with water and dried over magnesium sulfate, then the chloroform is removed by distillation under reduced pressure, and the residue is recrystallized from ethanol-ether to give 0.4 g of 2-dihydro- 6-methyl-5- (imidazo [1,2-a] pyridin-10-yl) -2-oxopyridine, mp 290-292 ° C.

Nuclear Magnetic Resonance Spectrum (DMSO-d 6): 12.62 (1H, b, S), 8.0 (1H, d, J = 1 Hz), 7.52 7.70 (3H, t-shaped), 7.4 (1H, d, J = 9.2 Hz), 7.06 (1H, dd, J = 2.10 Hz), 6.52 (1H, d, J = 9.2 Hz), 2.38 (3H , s).

«I • ·

Claims (2)

2i 91758 A process for the preparation of a 5- (6-imidazo [1,2-a] pyridyl) pyridine derivative or a tautomer thereof or a pharmaceutically acceptable salt thereof useful as a medicament, the derivative of which has the general formula (I) missäγ missä 15 in which R 1 represents a hydrogen atom or a methyl group and W represents a methyl or ethyl group, characterized in that a compound of general formula (II ') "VY1" "" j Y "25 H or a tautomer thereof is heated in an aqueous acid solution, in which radicals R1 and W have the meanings given above. meanings, 30 and converting the derivative, if desired, into a tautomer or a pharmaceutically acceptable salt thereof 22 91 758 l. , a total of up to 5 compounds of formula (I) ν-ιΛ α) W ^ N ^ OH 15 for R1 is a hydrogen atom or a methyl group and W is a methyl or ethyl group, k in the case of a water-based mixture and a mixture of compounds of formula (II ') 20 and ·) 25 H or a tautomer, in which the formula R1 and W are overturned by 30% and derived at the time of use tautomer eller account sitt farmaceutiskt siltpliga sait. 1 ·