FI58126C - FOERFARANDE FOER FRAMSTAELLNING AV KARDIOTONA OCH BLODTRYCKSSAENKANDE 2-PHENYL-1H-IMIDATSO (4,5-B) PYRIDINER - Google Patents

Description

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Patent-och registerstyrelsan 'Antekin uttagd oeh wUkrHt «i pubifcmd 29.08.80 ~ (32) (33) (31) Requested« importThe B-gtrd priorlMt 03.02.73 12.12.73 Federal Republic of Germany-Förbunds-republiken Tyskland (DE) P 2305339.6, P 2361757.k (71) Dr. Karl Thomae Gesellschaft mit beschränkter Haftung, D-7950 Bibe-rach / Riss, Federal Republic of Germany Förbundsrepubliken Tyskland (DE) (72) Eberhard Kutter, Biberach / Riss, Volkard Austel, Biberach Riss,

Willi Diederen, Rissegg, Saxony Federal Republic-Förbundsrepubliken Tyskland (DE) (7 * 0 Leitzinger Oy (5i +) Method for the preparation of cardiotonic and antihypertensive 2-phenyl-1H-imidazo [1 +, 5-b] pyridines - Förfarande tona och blodtryckssänkande 2-phenyl-1H-imidazo [1 +, 5-b] pyridine

The process for the preparation of cardiotonic and antihypertensive 2-phenyl-1H-imidazo [1,5-b] pyridines of the general formula I are isomers of the general formula Ia of R 'R5-C ^ 73' fV2 tn «4 3

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RsHfXX_ / v2 {Ia) wherein H is a methylamino, dimethylamino, morpholino or piperazine group, wherein the piperazine group of 2 581 26 1+ base is substituted with an alkyl group having 1 * 3 carbon atoms or. a phenyl group, a hydroxy, alkoxy, allyloxy, benzyloxy, alkylmercapto, alkylsulfinyl or alkylsulfonyl group, the alkyl group having 1 to 1 + carbon atoms, an alkoxy group having 2 or 3 carbon atoms substituted by a halogen atom, hydroxy, alkoxy, alkyl mercapto, alkylsulfinyl, alkylsulfonyl, dialkylamino, methylamino, piperidino, morpholino, thiomorpholino, N-methylpiperazino, N-phenylpiperazino, N-methoxyphenylpiperazine -, N-phenylethylpiperazino, phenylethylamino, N-methylethylethylamino or N-methyldimethoxyphenylethylamino, wherein the alkyl groups contain 1 or 2 carbon atoms R 2 is a hydrogen, fluorine or chlorine atom, methyl, hydroxy -, methoxy, ethoxy, propoxy, methylmercapto, methylsulfinyl or methylsulfonyl group, is a hydrogen atom, hydroxy or. methoxy group or 2 of R 1 -R 4 together form a methylenedioxy group, R 2 is a hydrogen atom, an alkyl group having 2 to 1 carbon atoms substituted by dimethylamino, piperidino, morpholino, N-methylpiperazino, N phenyl-piperazine-, N-phenylethyl or N-dimethoxyphenylethyl group, and R 1 is a hydrogen or chlorine atom or a methyl group, and their physiologically acceptable acid addition salts with inorganic or organic acids.

The above compounds of the general formula I and Ia have valuable pharmacological properties, in particular an effect on blood pressure, cardiac power, a positive inotropic effect, an antiulcer effect, an antiplatelet effect and a bleeding time-prolonging effect. These compounds can be prepared by the following methods:

Pyridine of general formula II <5 <rH2 wherein R1 is as defined above and 35126 Y is a halogen atom or an R1 -NH group having the same meaning as above is reacted with a compound of general formula III R1 R3 "wherein R1-R3 have the same meaning as above and X is a functional derivative of a carboxyl group.

Suitable functional acid derivatives are, in particular, nitrile, acid halide, ester, amide, imidic acid ester, imidic acid thioester, imidic acid halide, amidine, thio-carboxylic acid, dithiocarboxylic acid or n-carboxylic acid, N-carboxylic acid.

The reaction is conveniently carried out in a suitable solvent such as benzene, pyridine, glycol, toluene, acetone, diethylene glycol and triethylamine, optionally in the presence of an acid scavenger such as pyridine or triethylamine. Optionally, a catalytic amount of an acid such as p-toluenesulfonic acid and a dehydrating agent such as phosphorus oxychloride or thionyl chloride are also present. Depending on the reactivity of the group X, the reaction is carried out at temperatures between -20 and 250 ° C. However, the reaction can also be carried out without a solvent.

For example, if X represents a carboxyl group or an amide derivative, the reaction is conveniently carried out in the presence of phosphorus oxychloride or thionyl chloride and optionally a tertiary organic base such as pyridine or triethylamine, preferably at temperatures between -20 ° and the boiling point of the solvent used, for example 120 ° C.

For example, if X represents a nitrile group, 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 58126 at 180 ° C, for example 160 ° C, optionally in a solvent.

For example, if X represents a thioamide derivative, the reaction is conveniently carried out in a solvent such as glycol and preferably at temperatures of 100 to 150 ° C, for example 130 ° C.

If Y in a compound of general formula II represents a halogen atom, for example a chlorine atom, then the reaction proceeds via the corresponding amidine, which does not always have to be isolated and which is cyclized at elevated temperatures, for example from 100 to 200 ° C.

The compounds of the general formulas I and Ia obtained by the process according to the invention which contain a reactive halogen atom can subsequently, if desired, be converted into the corresponding amino compound by amine, and / or the obtained compounds of general formula I and Ia containing a reactive hydrogen atom can be subsequently alkylated with a base and a conventional alkylate. and / or the resulting compounds of the general formula I and Ia can be converted into the corresponding N-oxide, S-oxide or S, S-dioxide compounds by means of a conventional oxidizing agent and / or converted into physiologically acceptable acid addition salts by means of inorganic or organic acids , for example, hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, tartaric acid, maleic acid or fumaric acid have proved to be suitable acids.

The starting materials used in the process are known from the literature or can be prepared by methods known per se (see examples).

As already mentioned, the new compounds of the general formula I and Ia have valuable pharmacological properties, in particular they have an effect on blood pressure, they have a positive inotropic effect, an antiulcer effect, an anti-accumulation of blood cells! effect and prolonging the bleeding time.

For example, the biological effects of the following compounds were studied: A = 2- (2,4-dimethoxyphenyl) -1-imidazo [4,5-b] pyridine hydrochloride, B = 2- [2- (2-methylsulfinyl ethoxy) -4-methoxy-phenyl / -1H-imidazo [4,5-b] pyridine hydrochloride, 58126 C = 2- (2-methoxy-E-methylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine- ni hydrochloride, D = 2- (2-methoxy-U-methylsulfinyl-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, E = 2- (2-methoxy-5-methylmercapto-phenyl) - 1H-imidazo [1,5-b] pyridine hydrochloride, F = 2- (2-methoxy-E-methyl-phenyl) -1H-imidazo [5-b] pyridine hydrochloride, G = 2- (2 -ethoxy-E-methoxy-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, N, K = 2- (2-ethoxy-U-methyl-phenyl) -1H-imidazo [1,5-b / pyridine hydrochloride, I = 2- (2-netoxy-U-chloro-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, J = 2- [2- (2-methylsulfinyl-ethoxy) ) N-Methylmercapto-phenyl / -linine, i.e. A, 5-b / pyridine hydrochloride K = 2 (2A-deraethoxyphenyl) -7-methyl-1H-imidazo A, 5-b / pyridine hydrochloride L = 2- (t-methylmercaptophenyl) -3- (3-morpholinopropyl) -3H-iridazo [1,5-b] pyridine M = 2-phenyl-1H-imidazo> 5- b) pyridine hydrochloride K = 2- (U-methylphenyl) -1H-iridazo [1,5-b] pyridine O = 2-A-chlorophenyl) -1H-imidazo [5-b] pyridine hydrochloride 1. Positive inotropic effect in an isolated guinea pig atrium:

The isolated guinea pig vestibules were placed in a 100 ml oil bath. The bath was filled with a thyroid solution at 30 ° C. Carbogen gas (95% O 2 and 5% CO 2) was bubbled through the tyrod solution. Spontaneous atrial contractions were recorded isometrically with a Statham-Force transducer on a Grass polygraph. The vestibules were then loaded with one gram. After a sufficient equilibrium time, the test substances were added to the organ bath. The concentration of the substance in the organ bath was then 1 x 10 μg / ml in each case. 5 vestibules were used for each substance.

The results of the experiment are given in the following table: 6 58126

Table I

Compound Increase in contractile amplitude,% A 57.0 B 17.5 C 10.3 E 40.9 F 50.2 G 33.9 H 42.9 I 21.4 J 11.4 2. Circulatory test in anesthetized cats;

Cats were anesthetized using 30 mg / kg Pentobarbital sodium i.v. A plastic catheter was inserted into the femoral artery, and a steel catheter from Arteria carotis was inserted into the left ventricle. Arterial blood pressure and left ventricular pressure were continuously recorded with a P23AA and P23Dc type Statham pressure transducer. The contraction parameters dp / dt and V were continuously calculated from the chamber pressure curve using an analog computer. The heart rate was obtained with a tachograph from the chamber pressure curve. Besides, an ECG was recorded on another channel. All registrations were done with a Brush plotter. The substances were injected through an intravenous cannula into the femoral vein. Each substance was tested in at least three cats.

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The following are some comparative pharmacological experiments in which some of the compounds of the invention and theophylline have been compared.

AA * 2- (2, U-dimethoxy-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, BB * 2- (2,1-dihydroxy-phenyl) -1H-imidazo / U, 5-b / pyridine hydrochloride, CC 2- (2,1-dimethoxy-phenyl) -6-chloro-1H-imidazo [5,5-b] pyridine hydrochloride, DD * 2- (2,1 * -dimethoxy) -phenyl) -5-methyl-1H-imidazo [1,5-b] pyridine hydrochloride, EE = 2- (2-methoxy-3,5-methylenedioxyphenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, FF * 2- [2- (2-methoxy-ethoxy) -U-methoxy-phenyl] -1H-imidazo [1,5-b] pyridine hydrochloride, GG = 2 / 2- (2-methylsulfinyl) -ethoxy) -N-methoxy-phenyl / -1H-imidazo [1,5-b] pyridine, HH 2- (2- (2-methylmercaptoethoxy) -methoxy-phenyl) -1H-imidazoA, 5-b / pyridine hydrochloride, II * 2- [2- (3-ethylsulfinyl-propoxy) -N-methoxy-phenyl] -1H-imidazo [1,5-b] pyridine, JJ * 2- [2- (3-ethylmercapto-propoxy) -N-methoxy-phenyl] -1H-imidazo [1,5 '] pyridine hydrochloride, KK 2- (2-ethoxy-1 * -methylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, LL * 2- (2-methoxy-U-methylmercapto-phenyl) nyl) -1H-imidazo [1,5-b] pyridine, NM 2- (2-methoxy-14-methylsulfinyl-phenyl) -1H-imidazo [1,5-b] pyridine, NN * 2- (2-methoxy) -5-methylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, 9 58126 00 = 2- (2-methoxy-U-methyl-phenyl) -1H-imidazo [1,5] b / pyridine hydrochloride, PP * 2- (2-ethoxy-U-methoxy-phenyl) -1H-imidazoA, 5_b) pyridine hydrochloride, QQ = 2- (2-ethoxy-U-methyl-phenyl) -1H-imidazo (U, 5-b) pyridine hydrochloride, RR = 2- [2- (2-methylsulfinylethoxy) -U-methylmercapto-phenyl] -1H-iridazo-s] U * 5-b) pyridine, "SS = 2- (2-allyloxy-U-methoxy-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, TT = 2- (2-methoxy-U-butylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride, UU * 2- (2-ethoxy-U-butylsulfinyl-phenyl) -1H-imidazo [1,5-b] pyridine, N = = (2-butoxy-U-methyl-phenyl) -1H- imidazoA, 5-b / pyridine hydrochloride, WW * 2- (2-fluoro-U-methoxy-phenyl) -1H-imidazo, 5-b) pyridine hydrochloride, XX = 2-A-methoxy-2- (3 -chloro-propoxy) phenyl / -lH-imid azo (U, 5-b) pyridine, YY = 2- (2-methoxy-U-chlorophenyl) -1H-imidazoA, 5-b) pyridine hydrochloride, "ZZ = 2- (2-methoxy-U- methylamino-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride and N, N = 2- (2,1-dimethoxy-phenyl) -1H-imidazo-1,5'-pyridineoxy- )

The positive inotropic effect of the compounds has been investigated in comparative experiments, in which case rats have been used as experimental animals. Otherwise, the experiments were performed as described on page 5, however, so that the change in the contractile force as a function of the concentration of the test compound was measured in the experiment. The change was measured as a percentage of the initial value, where the EC ^ value shown in the following table means a minimum concentration that results in an increase of 50 ϊ: η in the contractile force. In addition, the toxicity of the compounds was measured according to LITCHFIIELD, J.T. and WILCOXXN, F. (J. Pharmakol. Exp. Ther. j) 6, page 99, 19-9). The table further shows the therapeutic index of the compounds which means the ratio LD50 q mg / kg: ec50 ug / ml.

10 581 26

Compound EC ^ Q ug / ml LD ^ Q mg / kg p.o. Terap. index AA 5.9 568 96.3 BB 37.0 1,250 33.8 CC 5.7 1 27O 222.8 DD 3.8 1 1 * 30 376 EE 5.6 350 63 FF 1.9 1 * 55 239 .5 GG 6.2 5 ^ 3 87.6 HH 2, U 650 270.8 ii 3M 650 19.1 JJ 8.8 1 200 136.1 * KK 2.6 1 1 * 00 538.5 LL 150 2 000 13 MM 33 560 17 NN 5.1 1 1 * 30 280 00 5.9 2 050 3 ^ 7.5 PP M 735 153.1 QQ 1.5 1 1 * 70 980.0 RR 2.8 1 * 00 11 + 3 SS 1 +, 7 538 111 *, 5 TT 32.0 65Ο 20.3 UU ll *, 0 1 * 50 32 W 6.2 1 69Ο 273 WW 20.0 1 69Ο 85 XX 0.8 650 813 YY 1 *, 3 630 11 + 6.5 zz 8.2 500 6l NIGHT 70 800 11.1 *

Theophylline 68 1 * 05 5.9 11 58126 In addition, none of the compounds had any toxic side effects at the dosages used.

The novel compounds of the general formula I and Ia can be processed for pharmaceutical use, optionally in combination with other active ingredients, into customary formulations, such as tablets, lozenges, suppositories, ampoules or drops. The unit dose is then from 35 to 200 mg, but preferably from 50 to 100 mg.

The following examples further illustrate the invention.

Example 1 "" 2- (2,4-Dimethoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 54.5 g of 2,3-diaminopyridine and 91.1 g of 2,4-dimethoxybenzoic acid are ground together to form a fine powder. and 1500 parts of any phosphorus oxychloride are added portionwise while stirring. After the addition, heat at reflux for 2 hours and distill off the phosphorus oxychloride in vacuo. The residue is triturated with 2000 ml of 2N hydrochloric acid, whereupon the precipitated solid is filtered off and recrystallized from water.

Yield 121 g (85% of theory), melting point! 238 ° C.

Example 2 2- (2,4-Dimethoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 360 mg of 2,4-dimethoxybenzoic acid are dissolved in 2 of any pyridine and a solution containing 220 mg of 2,3-diaminopyridine 2 is added. in ml of pyridine, whereupon the corresponding salt precipitates. While stirring and cooling on ice, 0.38 ml of phosphorus oxychloride is added dropwise. Stir for an additional hour at 0 ° C and one hour at room temperature. Excess pyridine is then removed in vacuo, the residue is taken up in dilute hydrochloric acid, neutralized with sodium hydroxide and extracted with ethyl acetate. The ethyl acetate phase is evaporated off, the residue is taken up in a small amount of 2N hydrochloric acid, the precipitate is filtered off and recrystallized from water.

Melting point 238-239 ° C.

12,581 26

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

Prepared according 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 hydrochloride 900 mg of 2,4-dimethoxy-benzoic acid are converted into the acid chloride by heating in a mixture of 3 ml of benzene and 2 ml of thionyl chloride. . It is then evaporated in vacuo and the residue obtained is taken up in 5 ml of benzene. This solution is added dropwise with stirring to a solution containing 550 mg of 2,3-diaminopyridine in 5 ml of pyridine. After the addition, heat briefly at 60 ° C, then cool to room temperature, dropwise add 0.9 ml of phosphorus oxychloride and stir for a further 3 hours at room temperature. Then 2N hydrochloric acid is added, neutralized and extracted with ethyl acetate. The ethyl acetate phase is evaporated and a small amount of 2N hydrochloric acid is added to the residue. The precipitated crystals are separated by suction and recrystallized from water. Melting point: 237-238 ° C.

Example 5 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride a) 2-Amino-3- (2,14-dimethoxy-benzoylamino) -pyridine hydrochloride 530 mg 2,4-Dimethoxybenzoic acid is converted to the acid chloride according 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. Stir at room temperature for another 2 hours. Water is then added to the mixture, neutralized with concentrated hydrochloric acid and extracted with ethyl acetate. The ethyl acetate is evaporated off, the residue is taken up in dilute hydrochloric acid, the precipitated crystals are filtered off with suction and recrystallized from ethanol.

Melting point: 172-174 ° C.

13,581 26 b) 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 155 mg of 2-amino-3- (2,4-dimethoxybenzoylamino) -pyridine- the hydrochloride is dissolved in 2 ml of pyridine. 0.2 ml of phosphorus oxychloride are added dropwise to the mixture at room temperature while stirring. After 2 hours, the mixture is poured into water and worked up according to Example 4.

Melting point: 237-238 ° C.

Example 6 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 155 mg of 2-amino-3- (2,4-dimethoxybenzoylamino) -pyridine hydrochloride the radium is heated for 5 minutes at 200-210 ° C. It is then treated with a small amount of 2N hydrochloric acid, filtered and recrystallized from water.

Melting point: 237-238 ° C.

Example 7 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 155 mg of 2-amino-3- (2,4-dimethoxybenzoylamino) pyridine hydrochloride heated in 2 ml of glycol for 30 minutes at reflux. It is then diluted with water, neutralized, extracted with ethyl acetate and worked up according to Example 4.

Melting point: 238-239 ° C.

Example 8 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 5.45 g of 2,3-diaminopyridine are added in small portions to 150 ml of phosphorus oxychloride with stirring and 9.81 g are added dropwise. 2,4-Dimethoxy-benzoic acid methyl ester. After the addition, heat at 120 ° C. After 2 hours, the phosphorus oxychloride is evaporated off under vacuum, the residue is triturated with 2N hydrochloric acid and the solid obtained is filtered off and recrystallized from water.

Melting point: 238-239 ° C.

581 26 14

Example 9 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride To 470 mg of 2,4-dimethoxybenzoyl chloride in 6 ml of toluene is added with stirring 0.5 ml of morpholine. After 20 minutes, the toluene is evaporated off, the residue is taken up in dilute hydrochloric acid and the mixture is extracted with ethyl acetate. After washing the ethyl acetate phase with bicarbonate solution, it is evaporated to give crude 2,4-dimethoxybenzoylmorpholine as an oil. This is taken up in 5 ml of pyridine, 250 mg of 2,3-diaminopyridine are added and finally 1 ml of phosphorus oxychloride is added dropwise with stirring and ice-cooling. Stir for 5 hours at 0 ° C and add ice water. Adjust to alkaline with concentrated ammonia, heat briefly on a steam bath and extract with ethyl acetate. The ethyl acetate is evaporated off, the residue obtained is treated with 2N hydrochloric acid, filtered off with suction and recrystallized from water.

Melting point: 238 ° C.

Example 10 2- (2,4-Dimethoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 300 mg of 2,4-dimethoxybenzoic acid (4-chloroanilide) and 110 mg of 2,3-diaminopyridine are mixed and added portionwise with stirring to 3 ml of phosphorus oxychloride. It is then heated at reflux for 8 hours, the phosphorus oxychloride is removed in vacuo, the residue is triturated with 2N hydrochloric acid, the solid formed is filtered off and recrystallized from water.

Melting point: 237-238 ° C.

Example 11 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 600 mg of 2,4-dimethoxybenzoic acid (4-chloroanilide) are heated at reflux for 3 hours in a mixture of 5 ml. benzene and 2 ml of thionyl chloride. After evaporation, crude 2,4-dimethoxy-N- (4-chlorophenyl) -benzimidic acid chloride is obtained in the form of an oil. This is taken up in 9 ml of toluene and added to a solution of 200 mg of 2,3-diaminopyridine in 5,812 6 in 10 ml of isopropanol. The mixture is heated at 70 ° C for 10 minutes. The resulting 2,4-dimethoxy-benzoic acid N- (4-chlorophenyl) -N'-C2-amino-3-pyridyl) -amidine hydrochloride is not isolated but, after evaporation of the isopropanol in vacuo, 20 ml are taken. to glycol and heat at reflux for 10 minutes. Water is then added, made alkaline with concentrated ammonia, extracted with ethyl acetate and worked up as in Example 4. Melting point: 237-238 ° C.

Example 12 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 100 mg of 2,3-diaminopyridine, 200 mg of 2,4-dimethoxybenzonitrile and 400 mg of p-toluenesulfonic acid monohydrate stirred and heated at 160 ° C for 3 1/2 hours. The product is then triturated with dilute ammonia and ethyl acetate until all is dissolved. The aqueous phase is extracted once more with ethyl acetate. The combined ethyl acetate phases are extracted with a small amount of 2N hydrochloric acid, after which the product crystallizes after some time.

Melting point: 237-238 ° C.

Example 13 2- (3,4,5-Trimethoxyphenyl) -1H-imidazo [4,5-b] pyridine 3.4 g of toluenesulfonic acid monohydrate and 15 ml of benzene are heated at 120 ° C until all the benzene has evaporated. 1.1 g of 2,3-diaminopyridine and 2 g of 3,4,5-trimethoxy-benzoic acid nitrile are then added. The mixture is heated at 150 ° C for 2 hours. After cooling, water is added, the mixture is extracted with ethyl acetate, the ethyl acetate phase is washed with dilute sodium hydroxide, evaporated and the residue is 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 refluxed in 40 ml of phosphorus oxychloride for 2 hours. The phosphorus oxychloride is then distilled off, ice water is added to the residue and the precipitated solid product is filtered off. The product is dissolved in hot water, made alkaline with concentrated ammonia, the precipitate is filtered off and recrystallized from a small amount of 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 is heated for 3 1/2 hours at 130 ° C and then dissolved in 300 ml of hot ethanol. Upon cooling, the precipitated product is recrystallized from ethanol.

Melting point: 127 ° C.

b) S-Methyl-2,5-dimethoxy-thiobenzoic acid morpholide iodide 6 g of 2,5-dimethoxy-thiobenzoic acid morpholide, 6.5 g of methyl iodide and 30 ml of acetone are heated at reflux for 8 hours. The precipitated solid is then filtered off and washed with ether and reacted directly again.

o) 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 in 30 ml of glycol for 40 minutes at 130 ° C. It is then poured into ice water, filtered 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 emorpholide

According to Example 15a, 12.2 g of 4-hydroxybenzaldehyde-dec 17,581 26 hydr, 16 g of morpholine and 3.2 g of sulfur are prepared.

Melting point: 205 ° C.

b) S-Methyl-4-hydroxy-thiobenzoic acid morpholide iodide

According to Example 15b, 14.4 g of 4-hydroxy-thiobenzoic acid morpholide and 2.1 g of methyl iodide in 100 ml of acetone are prepared. 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 and 1.1 g of 2,3- diaminopyridine in 30 ml of glycol is heated for 20 minutes at 130 ° C. Upon cooling, the precipitated product is dissolved in sodium hydroxide 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 hydrochloride) 4-Methoxy-2- (3-chloropropoxy) - benzoic acid morpholide 21.9 g of 2-hydroxy-4-methoxy-benzoic acid morpholide are dissolved in 200 ml of dimethylformamide and 11.2 g of potassium tert-butylate are added. After all is dissolved, 50 g of l- chloro-3-bromopropane and heated at 130 ° C for 2 hours. It is then evaporated in vacuo, the residue is taken up in ethyl acetate, washed with sodium hydroxide and water, evaporated and used directly for the next reaction.

b) 2- [4-Methoxy-2- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride 20 g of 4-methoxy-2- (3-chloropropoxy) benzoic acid morpholide, 7 g of 2,3-diaminopyridine and 170 ml of phosphorus oxychloride are heated at reflux for 2 hours. After evaporation of the phosphorus oxychloride, water is added to the residue, neutralized with sodium hydroxide, extracted with ethyl acetate and the hydrochloride is precipitated with ethereal hydrochloric acid.

Melting point: 198 ° C (decomposes).

18 58126

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 2 3.7 g of 2-hydroxy-4-methoxy-benzoic acid morpholide, 33.6 g of potassium tert-butylate and 37.4 g of ethylene bromohydrin in 100 ml of dimethylformamide are heated at 120 ° C for 6 hours: in. After evaporation in vacuo, take up in chloroform, wash with sodium hydroxide and water and evaporate.

b) 2- [4-methoxy-2- (2-chloroethoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride 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 refluxed for 2 hours. After evaporation, water is added, the mixture is neutralized, extracted with ethyl acetate and the hydrochloride is precipitated with ethereal hydrochloric acid.

Melting point: 110 ° C (decomposes).

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 tert-butylate and 20 ml of dimethylformamide are heated at 130 ° C for 2 hours. . It is then evaporated in vacuo, water is added and filtered.

Melting point: 87-90 ° C.

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

Prepared according to Example 17b from 4-methoxy-2- (3-chloropropoxy) -benzoic acid anilide and 2,3-diaminopyridine.

Melting point: 198 ° C.

19 581 26

Example 20 2-N-Methoxy-2- (3-morpholino-propoxy) -phenyl-1H-imidazo [1,5-b] pyridine__ 0.5 g of 2-A-methoxy-2- (3-chloropropoxy) -phenyl / -1H -inidazoA, 5-b-pyridine hydrochloride and 5 ml of morpholine are heated at reflux for 1.5 hours. Water is then added, filtered and recrystallized from water.

Melting point: 108-110 ° C.

Example 21 N-2-A-methoxy-2- (2- (4-phenyl-1-piperazinyl) -ethoxy) -phenyl 1H-imidazo A, 5-b / pyridine-1.7 g of 2-A-methoxy-2- (2-Chloroethoxy) -phenyl AlH-imidazo A, 5-b A pyridine and 3.2 g of phenylpiperazine are boiled in ethanol for 8 hours.

Melting point: 164-165 ° C (from isopropanol).

Example 22 2-A-Methoxy-2- (3-dimethylamino-propoxy) -phenyl] -1H-imidazo [1,5-b] pyridine hydrochloride 1.8 g of 2-A-methoxy-2- (3-chloropropoxy) -phenylAlH- inidazoA, S-bA pyridine hydrochloride and 20 ml of a saturated solution of dimethylamine in ethanol are heated in a bomb for 8 hours at 100 ° C. It is then evaporated in vacuo and recrystallized from isopropanol. Melting point: 209-210 ° C.

Example 23 2-M-Methoxy-2- (3-dimethylamino-propoxy) -phenyl] -1H-imidazo [1,5-b] pyridine dihydrochloride__ 1.64 g of 4-methoxy-2- (3-dimethylamino-propoxy) - thiobenzoic acid morpholide is dissolved in a mixture of 17 ml of glacial acetic acid and 3 ml of acetic anhydride, 1 ml of dimethyl sulphate is added and the mixture is heated for 1 hour in a steam bath. It is then evaporated in vacuo. The crude S-methyl-4-methoxy-2- (3-dimethylamino-propoxy) -thiobenzoic acid norfolide methyl sulfate obtained is taken up in 13 ml of glycol, 0.7 g of 2,3-diaminopyridine is added and the mixture is heated at 160 [deg.] C. for 2 hours. C. It is then poured into 50 ml of water, 5 ml of concentrated ammonia are added and the mixture is extracted with ethyl acetate. The ethyl acetate phases are evaporated, the residue is taken up in ethanol, ethereal hydrochloric acid is added and re-evaporated. The residue solidifies on trituration with toluene and a small amount of ethanol. Separate by suction and recrystallize from iso-propanol.

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

Example 24 2- (2,4-Dimethoxy-phenyl) -3-methyl-3H-imidazo [4,5-b] pyridine 800 mg of 2,4-dimethoxybenzoic acid methylamide and 500 mg of 2-chloro-3-aminopyridine in 10 ml in phosphorus oxychloride is heated at reflux for 3 hours. It is then poured into water, neutralized with concentrated ammonia and extracted with ethyl acetate. The crude N-methyl-N '- (2-chloro-3-pyridyl) -2,4-dimethoxybenzamidine obtained on evaporation is taken up in 10 ml of 10% glycol-containing sodium hydroxide and heated at 180-190 ° C for 4 hours. The mixture is poured into water, extracted with ethyl acetate and purified on a column (silica gel, eluent * CHCl3. MeOH = 19: 1).

Melting point of hydrochloride: 196-197 ° C.

Example 25 2- (2,4-Dimethoxy-phenyl) -3- (4-chloro-phenyl) -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 are heated at reflux for 2 hours in 16 ml of phosphorus oxychloride. It is then poured into water, neutralized with concentrated ammonia and extracted with ethyl acetate. The ethyl acetate phase is extracted with 3N hydrochloric acid. After neutralization of the aqueous phase, it is re-extracted with ethyl acetate. The solid product remaining on evaporation is recrystallized from methanol.

Melting point: 176-178 ° C.

21 58126

Example 26 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 2.2 g of 2,3-dianinopyridine, 6.8 g of 2,4-dimethoxybenzoic acid morpholide imide dichloride and 12 ml of triethylamine in 10 ml of diethylene glycol dimethyl ether are heated for 1/2 hour at 120 ° C. After cooling, water is added to the reaction mixture, extracted with chloroform and the chloroformase is shaken with 2N hydrochloric acid. The yellow hydrochloride precipitated from the hydrochloric acid solution is liberated with ammonia and purified by column chromatography.

The hydrochloride is reprecipitated in acetone with ethereal hydrochloric acid.

Melting point: 237-238 ° C,

Example 27 2- (2,4-Dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 1.1 g of 2,3-diaminopyridine and 3.5 g of 2,4-dimethoxybenzoic anhydride are heated. hours at 180 ° C.

Further processing is carried out according to Example 26.

Melting point: 236-238 ° C.

Example 28 2- (2-Methoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride - a) 2-Methoxy-benzoic acid thiomorpholide 34 g of 2-methoxybenzaldehyde, 16 g of sulfur and 32.6 g of morpholine are heated 3 hours at 120 ° C. The reaction mixture thus obtained is taken up in ethanol, filtered, cooled and the precipitated yellow crystals are filtered off with suction.

Yield: 54.1 g (91% of theory), melting point: 80-82 ° C.

b) 2-Methoxy-benzoic acid thiomorpholide methiodide 47.4 g of 2-methoxy-benzoic acid thiomorpholide in 150 ml of acetone and 25 ml of methyl iodide are heated at reflux for 1 hour. After cooling 22 5812 6, the precipitated yellow crystals are filtered off with suction.

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

c) 2- (2-Netoxyphenyl) -1H-indidazo [4,5-b] pyridine 19 g of 2-methoxy-benzoic acid thiomorpholide-metiodide and 8.7 g of 2,3-diaminopyridine are heated in 70 ml of glycol for 3 hours. 120 ° C. After cooling, water is added, the mixture is adjusted to ammonia content and extracted with chloroform. The organic phase is washed with water and then 2N hydrochloric acid is added. The precipitated product is filtered off with suction, the base is liberated again with ammonia, taken up in chloroform and purified on a silica gel column.

The colorless hydrochloride is obtained from acetone by adding ethereal hydrochloric acid.

Melting point: 233-23 ° C.

Example 29 2- (2-Methoxyphenyl) -3-methyl-3H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2-methylamino-3-anino-pyridine and 2-methoxy-benzoic acid thiomorpholide methiodide.

Melting point: 208-210 ° C.

Example 30 2- [2- (2-Methoxy-ethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2- (2-methoxy-ethoxy) -benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

Melting point: 170-172 ° C.

Example 31 2- (4-Methoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 4-methoxy-benzoic acid thiomorpholide-metioiodide (melting point: 142-144 ° C) and 2,3-diaminopyridine. Melting point: 243-245 ° C.

23 581 26

Example 32 2- (3-Methoxy-4-hydroxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride ________________________

Prepared according to Example 28 from 3-methoxy-4-hydroxy-benzoic acid thiomorpholide methiodide (melting point: 178-180 ° C) and 2,3-dianino-pyridine.

Melting point: 251-25 U ° C.

Example 33 2- (2'-Dimethoxy-phenyl-1H-imidazo [1,5-b] pyridine hydrochloride ✓

Prepared according to Example 28 from 2,3-dimethoxy-benzoic acid thiomorpholide methiodide (melting point: 138-140 ° C) and 2,3-diaminopyridine.

Melting point: 270-272 ° C.

Example 3U

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

Prepared according to Example 28 from 2-hydroxy-1 + -methoxy-benzoic acid thiomorpholide net iodide (melting point: 180-181 ° C) and 2,3-diaminopyridine system.

Melting point: 190-192 ° C (decomposes).

. . o

Melting point of free base: 292-293 C.

Example 35 2- (2,1'-Dimethoxy-phenyl-1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2,4-dimethoxybenzoic acid thiomorpholide methiodide (melting point: 138-140 ° C (decomposes)) and 2,3-diaminopyridine.

Melting point: 238 ° C (from methanol).

Example 36 24 5 8 1 2 6 2- (2-N-Dimethoxy-phenyl) -G-methyl-1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2,3-diamino-5-methyl-pyridine and 2,4-dimethoxy-benzoic acid thiomorpholide methiodide.

Melting point: 260-261 ° C.

Example 37 2- (2,6-Dimethoxy-phenyl) -N-methyl-1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2,3-diamino-U-methyl-pyridine and 2,4-dimethoxy-benzoic acid thiomorpholide methiodide.

Melting point: 230-231 ° C.

Example 38 2- (2,4-Dimethoxy-phenyl) -5-methyl-1H-imidazo [+, 5-b] pyridine hydrochloride

Prepared according to Example 28 from 2,3-diamino-6-methyl-pyridine and 2,4-dimethoxy-benzoic acid thiomorpholide methiodide. Melting point: 2U5-246 ° C.

Example 39 2- (2,4-Dimethoxy-phenyl) -6-chloro-1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 "from 2,3-dianino-5-chloropyridine and 2,4-dimethoxy-benzoic acid thiomorpholide methiodide.

Melting point: 253-255 ° C.

Example UO

2- (2-Ethoxy-4-methoxy-phenyl) -1H-imidazo [14,5-b] pyridine hydrochloride _______ 25 5 81 2 6

Prepared according to Example 28 from 2-ethoxy-4-netoxy-benzoic acid thiomorpholide net iodide (melting point: 152-154 ° C) and 2,3-diaminopyridine.

Melting point: 228-230 ° C.

Example UI

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

Prepared according to Example 28 from 2-methoxy-4-ethoxy-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

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

Example 42 2- (2,4-Diethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2,4-diethoxy-benzoic acid thio-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 hydrochloride

Prepared according to Example 28 from 2- (2-hydroxy-ethoxy) -4-methoxy-benzoic acid thiomorpholide 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 hydrochloride _______

Prepared according to Example 28 from 2- (3-hydroxy-propoxy) -4-methoxy-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

Melting point: 170 ° C (sintered).

26 581 26

Example 45 2- [2- (2-Methoxy-ethoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2- (2-methoxy-ethoxy) -4-methoxy-benzoic acid thiomorpholide methiodide and 2,3-dianinopyridine. Melting point: 191-193 ° C.

Example 46 2- (2-Methoxy-4- (2-methylmercaptoethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride (a) 4- (2-methylmercaptoethoxy) -2- hydroxybenzaldehyde 12 g of 2,4-dihydroxybenzaldehyde and 9.6 g of potassium tert-butylate are dissolved in 50 ml of ethylene glycol monomethyl ether, 9.6 g of methyl mercaptoethyl chloride are added and the reaction mixture is stirred for 8 hours at 80 ° C (bath temperature). After removal of the solvent, the residue is taken up in dilute sodium hydroxide, the mixture is extracted twice with chloroform, the aqueous alkaline solution is separated, acidified, extracted with chloroform, dried and evaporated. The residue is purified by column chromatography (silica gel). The oil thus obtained is directly further processed.

b) 4- (2-methylmercaptoethoxy) -2-netoxybenzaldehyde 9.7 g of 4- (2-methylmercaptoethoxy) -2-hydroxybenzaldehyde and 6.7 g of potassium tert-butylate are dissolved in ethanol, added 4.3 ml of dimethyl sulfate and heated at reflux for 3 hours. An additional 1 ml of dimethyl sulfate is then added and heated again for one hour. After distilling off the ethanol, the residue is taken up in water / chloroform, 2N sodium hydroxide is added, the chloroform phase is separated off, washed with water, dried and evaporated.

Melting point: 99-100 ° C (from cyclohexane).

c) 4- (2-Methylmercapto-ethoxy) -2-methoxy-benzoic acid thionorphoid

Prepared according to Example 28a from 4- (2-methylmercaptoethoxy) -2-methoxybenzaldehyde.

Melting point: 131-132 ° C (from ethanol).

9 π 58126 cl) 2- [2-methoxy-4- (2-methylmercapto-ethoxy) -phenyl] -1K-imidazo [4,5-b] pyridine hydrochloride 5.4 g 4- (2-methylmercapto) -ethoxy) -2-methoxy-benzoic acid-thiomorpho-Lid and 1.2 ml of methyl iodide in 50 ml of acetone are heated at reflux for 1.5 hours. After cooling, the solvent is removed and the resulting syrupy methiodide and 3.6 g of 2,3-diaminopyridine in 20 ml of glycol are heated at 120 ° C for 1.5 hours. Dilute with water and shake with chloroform. 2N Hydrochloric acid is then added to the organic phase and the precipitated yellow precipitate is filtered off with suction.

Melting point: 197-199 ° C (from methanol).

Example 47 2- (2-Methoxy-4- (2-ethylmercapto-ethoxy) -phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 46 from 4- (2-ethylmercapto-ethoxy) -2-methoxy-benzoic acid thiomorpholide and 2,3-diaminopyridine. The final product is purified by chromatography on silica gel. Precipitation of the hydrochloride is carried out by dissolving the base in acetone and adding an excess of ethereal hydrochloric acid.

Melting point: 195-196 ° C.

Example 48 2- [2-Methoxy-4- (3-methylmercaptopropoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 46 from 4- (3-methylmercapto-propoxy) -2-methoxy-benzoic acid thiomorpholide and 2,3-diaminopyridine. Melting point: 189-191 ° C (decomposes).

Example 49 2- (2-Methoxy-4- (3-ethylmercaptopropoxy) -phenyl] -1H-indidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 46 from 4- (3-ethylnercapto-propoxy) -2-methoxy-benzoic acid thionorphoid and 2,3-diaminopyridine. Melting point: 183-185 ° C (decomposes).

28 581 26

Example 50 2- [2- (2-Methylmercapto-ethoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride___

Prepared according to Example 46 from 2- (2-methylmercapto-ethoxy) -4-methoxy-benzoic acid thiomorpholide and 2,3-diaminopyridine. Melting point: 204-206 ° C (decomposes).

Example 51 2- [2- (2-Ethylmercapto-ethoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 46 from 2- (2-ethylmercapto-ethoxy) -4-netoxy-benzoic acid thiomorpholide and 2,3-diaminopyridine. Melting point: 193-195 ° C.

Example 52 2- [2- (3-Methylmercapto-propoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 46 from 2- (3-methylmercapto-propoxy) -4-methoxy-benzoic acid thiomorpholide and 2,3-diaminopyridine. Melting point: 191-930C.

Example 53 2- [2- (3-Ethylmercaptopropoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 46 from 2- (3-ethylmercapto-propoxy) -4-methoxy-benzoic acid thiomorpholide and 2,3-diaminopyridine. Melting point: 187-189 ° C.

Example 54 2- (2,3,4-Trimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 29,581 2 6

Prepared according to Example 28 from 2,3,4-trimethoxy-benzoic acid thiomorpholide methiodide (melting point: 147-150 ° C) and 2,3-diaminopyridine.

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

Example 55 2- (2-Methoxy-3,4-methylenedioxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride _______________________________________

Prepared according to Example 28 from 2-methoxy-3,4-methylenedioxy-benzoic acid thiomorpholide methiodide (melting point: 109-111 ° C) and 2,3-diaminopyridine.

Melting point: 266-268 ° C.

Example 56 2- (2,4-Dimethoxy-3-hydroxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2,4-dimethoxy-3-hydroxybenzoic acid> thiomorpholide methiodide and 2,3-diaminopyridine. Melting point: 115-118 ° C.

Example 57 2- (2-Methoxy-14-chloro-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2-methoxy-4-chloro-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

Melting point: 302-305 ° C.

Example 58 2- (2-Methoxy-t + -methyl-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2-methoxy-4-methyl-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

Eating point: 256 ° C (decomposes).

Example 59 30 5 81 2 6 2- (2-Ethoxy-4-methyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride _____

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

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

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

Prepared according to Example 28 from 2-hydroxy-U-methylmercapto-benzoic acid morpholide (melting point: 124-129 ° C) and 2,3-diaminopyridine.

Melting point: 232-234 ° C.

Example 61 2- (2-Netoxy-5-methylnercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 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-ethylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2-methoxy-4-ethylmercapto-benzoic acid morpholide and 2,3-diaminopyridine.

Melting point: 215-217 ° C.

Example 63 31 58126 2- (2-Methylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2-methylmercapto-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

Melting point: 185-187 ° C.

Example 6U

2- (2,4-Bismethylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride (P ')

Prepared according to Example 28 from 2,4-bismethylnercapto-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine. Melting point: 2H9-250 ° C,

Example 65 2- [2- (2-Methylmercapto-ethoxy) -4-methyl-mercapto-phenyl] -1H-imidazo [H, S-b] pyridine hydrochloride

Prepared according to Example 28 from 2- (2-methylmercapto-ethoxy) -N-methylmercapto-benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine.

Melting point: 180-182 ° C.

Example 66 2- [2- (2-Diethylamino-ethoxy) -4-methyl-phenyl] -1H-imidazo [1,5-b] pyridine dihydrochloride___

Prepared according to Example 28 from 2- (2-diethylamino-ethoxy) -N-methyl-benzoic acid thiomorpholide-metioiodide hydrochloride and 2,3-diaminopyridine.

Melting point: 221-223 ° C.

Example 67 2- (2-Allyloxy-4-methoxy-phenyl) -1H-imidazo [1,5-b] pyridine-hydro-32 5 8 1 26 16.5 g of 2-allyloxy-4-methoxy-benzoic acid morpholide and 7 1 g of 2,3-diaminopyridine is mixed well and ground. 30 ml of phosphorus oxychloride are then added dropwise with stirring. The reaction mixture is then heated at reflux for 3 hours, the phosphorus oxychloride is removed and the residue is decomposed with ice water. The ammonia-adjusted solution is extracted with chloroform, the organic solution is shaken with 2N hydrochloric acid, adjusted once more to an ammonia-containing solution. Extract again with chloroform, dry the chloroform solution, treat with activated carbon / tonsil, filter and evaporate. The residue is dissolved in acetone and the pale yellow-colored hydrochloride is precipitated with ethereal hydrochloric acid.

Melting point: 189-191 ° C.

Example 68 2- (2 ', 4,5-Trimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride a) 2- (2,4,5-Trimethoxy-phenyl) -1,3-dithiolane-iodide 50 g of 1,2,4-trinetoxybenzene and 150 g of 2-methylmercapto-1,3-di-thiolane methosulphate are stirred in 600 ml of glacial acetic acid for 4 hours at a bath temperature of 70 ° C. The residue is dissolved in a mixture of chloroform and water, an excess is added to the aqueous phase potassium iodide solution, whereupon the product differs as orange crystals which can be directly further reacted.

b) 2- (2,4,5-Trimethoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 3.8 g of 2- (2,4,5-trimethoxyphenyl) -1,3-dithiolane iodide and 2.2 g of 2,3-diaminopyridine in 40 ml of glycol are heated for 10 minutes at 200 ° C. After cooling, it is extracted with ether and then with chloroform. The chloroform phase is shaken with 2N hydrochloric acid, the precipitated yellow hydrochloride is filtered off with suction and recrystallized from glycol.

Melting point: 278-280 ° C.

Example 69 2- (2,4,6-Trimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 33,581 26 a) 2 - :( 2,4,2-trimethoxy-phenyl) -1 , 3-dithiolane iodide 33.6 g of phloroglucin trimethyl ether and 105 g of 2-methylmercapto-1,3-dithiolane methosulphate are kept for 6 hours in 200 ml of glacial acetic acid at 75 ° C and the crystals which have separated overnight after standing are separated by suction and dissolved in water. Iodide is precipitated with potassium iodide solution.

Melting point: 153-154 ° C.

b) 2- (2,4,6-Trimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 4 g of 2- (2,4,6-trimethoxy-phenyl) -1,3 -dithiolanium iodide, 2.2 g of 2,3-diaminopyridine and 5 g of lead acetate in 75 ml of glycol are heated for 10 minutes. The precipitated lead salt is then filtered off with suction, the filtrate is diluted with water and the precipitated product is filtered off with suction. The product is dissolved in methanolic hydrochloric acid and purified on 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 hydrochloride

Prepared according to Example 69 from 3-hydroxy-4- [1 ', 3'-dithia-cyclopentylidene- (2') / - cyclohexadien- (2,5) -one- (1) and 2,3-diaminopyridine .

Melting point: 298-301 ° C.

Example 71 2- (4-Dimethylamino-phenyl) -1K-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 69 from 2- (4-dimethylamino-phenyl) -1,3-dithiolane-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-b] pyridine hydrochloride 345 81 2 6 a) 2- (2-Methoxy-4-dimethylamino-phenyl) - 1,3-Dithiolanium iodide 22.6 g of 3-dimethylaminoanisole, 43.2 g of 2-methylmercapto-1,3-di-thiolane methosulphate, 150 ml of glacial acetic acid and 22.5 ml of pyridine are heated at reflux for 1/2 hour. . After cooling, it is poured into aqueous potassium iodide solution, the precipitated product is filtered off with suction and dried.

Melting point: 189-195 ° C (from dimethylformamide).

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

Prepared according to Example 42 from 2- (2-methoxy-4-dimethylamino-phenyl) -1,3-dithiolane-iodide and 2,3-diaminopyridine. Melting point: 258-260 ° C (from methanol).

Example 73 2- (2-Methylsulfinyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 1.35 g of 2- (2-methylnercapto-phenyl) -1H-imidazo [4,5-b] / pyridine is dissolved in 20 nl of glacial acetic acid and 0.64 g of 30% hydrogen peroxide dissolved in 5 ml of glacial acetic acid are added dropwise. After standing overnight, it is diluted with water, neutralized with sodium bicarbonate and the precipitated product is filtered off with suction and dried. The colorless hydrochloride is obtained by adding ethereal hydrochloric acid to a methanolic solution of the compound.

Melting point: 205-210 ° C.

Example 74 2- (2-Methylsulfonyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 450 mg 2- (2-methylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride and 370 mg of 30% hydrogen peroxide are heated in 20 ml of glacial acetic acid for 3 hours at 70 ° C. After evaporation and trituration with petroleum ether, the desired product precipitates.

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

Example 75 35 5 812 6 2- [2- (2-Methylsulfinyl-ethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride) 2- [2- (2-methylmercapto-ethoxy) - phenyl / 1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 28 from 2- (2-methylmercapto-ethoxy) -benzoic acid thiomorpholide methiodide and 2,3-diaminopyridine. Melting point: 138-140 ° C.

b) 2- [2- (2-Methylsulfinyl-ethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride 4.3 g of 2- [2- (2-methylmercapto-ethoxy) ) -phenyl-1H-imidazo [4,5-b] pyridine hydrochloride and 1.5 g of 30% hydrogen peroxide are stirred in 100 ml of glacial acetic acid at room temperature for 2 hours and the batch is allowed to stand overnight. It is then diluted with water, neutralized with bicarbonate and extracted with chloroform. The chloroform phase is evaporated, the residue is taken up in acetone and the hydrochloride is precipitated with methanolic 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 according to Example 75b from 2- [2- (2-methylmercaptoethoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 231-232 ° C.

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

Prepared according to Example 75b from 2- [2- (2-ethylmercaptoethoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride.

Melting point: 188-189 ° C.

36 5 81 26

Example 78 2- [2- (3-Methylsulfinyl-propoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine _______

Prepared according to Example 75b from 2- [2- (3-methylmercaptopropoxy) -4-methoxyphenyl] -1H-indidazo [4,5-b] pyridine hydrochloride. Melting point: 132-133 ° C.

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

Prepare 2- [2- (3-ethylmercaptopropoxy) -4-methoxy-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride according to Example 75b, Melting point: 126-127 ° C.

Example 80 2- (2-Methoxy-4-methylsulfinyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 6.6 g of 2- (2-netoxy-4-methylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine is dissolved in 100 ml of chloroform and a solution containing 2.96 g of 3-chloroperoxybenzoic acid in 600 ml of chloroform is added dropwise over 5 hours at -15 ° C to 20 ° C. It is then shaken with dilute sodium hydroxide solution, the chloroform phase is dried and evaporated. The residue is purified on a silica gel column (eluent: chloroform / methanol = 9: 1). Addition of ethereal hydrochloric acid to the methanolic base solution gives a yellow hydrochloride. Melting point: 154-155 ° C.

Example 81 2- (2-Methoxy-4-methylsulfonyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride ____

Prepared according to Example 74 from 2- (2-methoxy-4-methylmercaptophenyl) -11-imidazo [4,5-] pyridine hydrochloride.

Melting point: 240-242 ° C.

Example 82 2- (2-Methoxy-4-ethylsulfinyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 5,8126

Prepared according to 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-methyl-mercapto-phenyl] -1H-imidazo [4,5-b] pyridine _________________

Prepared according to Example 80 from 2- [2- (2-methylmercaptoethoxy) -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 according to Example 80 from 2- [2- (2-methylsulfinyl-ethoxy> -4-methyl-mercapto-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 hydrochloride___

Prepared according to Example 75b from 2- [2- (2-methylmercaptoethoxy) -4-methyl-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 191-192 ° C (from acetone / ether).

38 5 8 1 26

Example 86 2- [2- (2-Methylsulfinyl-ethoxy) -4-chloro-phenyl] -1H-indidazo [4,5-b] pyridine hydrochloride

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

Example 87 7-12-Methoxy-4- (2-methylsulfinyl-ethoxy) -phenyl] -1H-imidazo [4 H 5 -b] pyridine_

Prepared according to Example 75b from 2- [2-netoxy-4- (2-methylmercaptoethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride.

Melting point: 204-205 ° C.

Example 88 2- [2-Methoxy-4- (2-ethylsulfinyl-ethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine_

Prepared according to 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 according to Example 75b from 2- [2-methoxy-4- (3-methyl-mercaptopropoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 179-180 ° C.

Example 90 2- [2-Methoxy-4- (3-ethylsulfinyl-propoxy) -phenyl] -imidazo [4,5-b] pyridine hydrochloride ______ 39 5 8 1 26

Prepared according to Example 75 from 2- [2-methoxy-4- (3-ethylmercaptopropoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 167-168 ° C.

Example 91 2- (2-Methoxy-5-methylsulfinyl-phenyl) -1H-imidazo [4,5-b] pyridine

Prepared according to Example 80 from 2- (2-methoxy-5-methylmercapto-phenyl) -1H-indidazo [4,5-b] pyridine hydrochloride.

Melting point: 211-212 ° C.

Example 92 2- (2-Methoxy-5-methylsulfonyl-phenyl) -1H-imidazo [4,5-b] pyridine

Prepared according to 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 1,5-b / pyridine and 1.35 g of 3-chloroperbenzoic acid are stirred in 15 ml of glacial acetic acid for 15 hours at 50 ° C. It is then recrystallized from 2N acetic acid by adding activated carbon. Clean by boiling with acetone.

Melting point: 266-267 ° C.

Example 94 2- (2,4-Dimethoxy-phenyl) -3-methyl-3H-imidazo [4,5-b] pyridine hydrochloride 3.5 g of 2- (2,4-dimethoxy-phenyl) -1H-imidazo (4,5-b) pyridine hydrochloride and 2.7 g of potassium tert-butylate are added to 40 ml of dimethylformamide and 3.6 g of methyl iodide are added dropwise. It is then stirred for a further two hours at room temperature, evaporated, the residue is taken up in chloroform / water, the organic phase is separated, dried and evaporated. The product is purified by column chromatography and then mixed with ethereal hydrochloric acid from acetone solution. Melting point: 196-197 ° C.

Example 95 2- (2-Hydroxy-phenyl) -3-methyl-3H-imidazo [4,5-b] pyridine hydrochloride___

Prepared according to 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-hydroxy-propyl) -3H-imidazo [4,5-b] pyridine hydrochloride _________________

Prepared according to Example 94 from 2- (2-hydroxy-4-methoxy-phenyl) -1H-imidazo [4,5-b] pyridine and 3-bromo-propanol.

Melting point: 154-155 ° C.

Example 97 2- (2,4-Dimethoxy-phenyl) -3-benzyl-3H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 94 from 2- (2,4-dimethoxy-phenyl) -1H-indidazo [4,5-b] pyridine.H and benzyl bromide.

Melting point: 148-150 ° C.

Example 98 2- (2,4-Dimethoxy-phenyl) -3- (2-diethylamino-ethyl) -3H-imidazo [4,5-b] pyridine dihydrochloride

Prepared according to Example 94 from 2- (2,4-dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine from H and 2-diethylamino-ethyl chloride at 80 ° C.

Melting point: 18 ° C.

2- (2,4-Dimethoxy-phenyl) -3- (3-dimethylaminopropyl) -3H-imidazo [4,5-b] pyridine dihydrochloride_41

Example 99 581 26

Prepared according to Example 94 from 2- (2,4-dimethoxy-phenyl) -1H-imidazo [4,5-b] pyridine and 3-dimethylaminopropyl bromide at 70 ° C.

Melting point: 190-192 ° C (decomposes).

Example 100 2- (2-Methoxy-4-benzyloxy-phenyl) -1H-imidazo [4,5-b] pyridine

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

Melting point of hydrochloride: 218-219 ° C (decomposes).

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

Prepared according to Example 10 from 2,4-dimethoxy-benzoic acid morpholide and 3-amino-2-butylaminopyridine.

Melting point of the hydrochloride: 218-219 ° C.

Example 102 2- (2-Methoxy-4-hydroxy-phenyl) -1H-imidazo [4,5-b] pyridine

Prepared according to Example 10 from 2-methoxy-4-hydroxy-benzoic acid morpholide and 2,3-diaminopyridine.

Melting point of the hydrochloride: 230-231 ° C.

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

Prepared according to Example 10 from 2-ethoxy-4-ethylmercapto-benzoic acid morpholide and 2,3-diaminopyridine.

Melting point of the hydrochloride: 198-199 ° C (decomposes).

Example 104 42 581 26 2- (4-Methoxy-2- (3- (4-methyl-1-piperazinyl) -propoxy) -phenyl] -1H-imidazo [4,5-b] pyridine_

Prepared according to Example 21 from 2- [4-methoxy-2- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine and 1-methylpiperazine. Melting point of trihydrochloride: 248 ° C (decomposes).

Example 105 2- (4-Methoxy-2- (2-thiomorpholino-ethoxy) -phenyl) -1H-imidazo [4,5-b] pyridine_

Prepared according to Example 21 from 2- [4-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-b] pyridine

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

Hydrochloride melting point: 237-238 ° C (decomposes)

Example 107 2- (4-Fluoro-2-methoxy-phenyl) -1H-imidazo [4,5-b] pyridine

Prepared according to Example 1 from 4-fluoro-2-methoxybenzoic acid and 2,3-diaminopyridine.

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

43

Example 108 2- (2-Hydroxy-4-methoxy-phenyl) -3-phenyl-3H-imidazo [4,5-b] pyridine 58126 4.9 g of 2-hydroxy-4-methoxy-benzanilide and 2.6 g of 2-Chloro-2-aminopyridine is heated at reflux in 50 ml of phosphorus oxychloride for 1 1/2 hours. After distilling off the phosphorus oxychloride, 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 according to 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 according to Example 108 from N- (4-methoxy-phenyl) -2-hydroxy-4-methoxy-benzamide and 2-chloro-3-aminopyridine. Melting point: 175 ° C.

Example 111 2- (2-Hydroxy-4-methoxy-phenyl) -3- (2-phenylethyl) -3H-imidazo- (4,5-b) pyridine_

Prepared according to Example 108 from N- (2-phenylethyl) -2-hydroxy-4-methoxybenzamide and 2-chloro-3-aminopyridine. Melting point: 155 ° C.

44

Example 112 2- (2,4-Dimethoxy-phenyl) -3-phenyl-3H-imidazo [4,5-b] pyridine 58126

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

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 according to Example 112 from N- (2-methoxy-phenyl) -N '- (2-chloro-3-pyridyl) -2H-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 according to 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 according to Example 112 from N- (3,4-dimethoxy-phenyl) -N '- (2-chloro-3-pyridyl) -2,4-dimethoxy-benzamidine.

Melting point: 190 ° C.

Example 116 45 5 812 6 2- (3,4-Dimethoxy-phenyl) -3- (4-methoxy-phenyl) -3H-imidazo [4,5-b] pyridine _____

Prepared according to Example 112 from N- (4-methoxy-phenyl) -N '- (2-chloro-3-pyridyl) -2,4-dimethoxy-benzamidine 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 according to Example 112 from N- (3-morpholino-1-propyl) -N '- (2-chloro-3-pyridyl) -2,4-dimethoxybenzamidine.

Melting point: 207 ° C.

Example 118 2- (2,6-Dimethoxyphenyl) -1H-imidazo [4,5-b] pyridine hydrochloride 9.1 g of 2,6-dimethoxybenzoic acid and 5.5 g of 2,3-diaminopyridine are heated to 100 ° C. in 1 ml of phosphorus oxychloride at reflux for 3 hours, then the phosphorus oxychloride is removed on a rotary evaporator and the residue is carefully decomposed with ice water. The resulting solution is filtered, neutralized with potassium carbonate and made alkaline with concentrated ammonia. The resulting suspension is taken three times with chloroform, the chloroform phase is dried over magnesium sulfate, filtered, the solvent is removed and the remaining residue is dissolved in 50 ml of methanolic hydrochloric acid. Then add 100 ml of isopropanol and store overnight in the freezer. The precipitate formed is filtered off with suction and washed with ether.

Melting point: 250-254 ° C.

Example 119 2- (2-Propoxy-4-methyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride ______________ 46 5 81 2 6

Prepared according to Example 118 from 2-propoxy-4-methyl-benzoic acid pomorpholide.

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

Example 120 2- (2-Butoxy-4-methyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 113 from 2-butoxy-α-methyl-benzoic acid morpholide.

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

Example 121 2- (α-Methylmercapto-phenyl) -1H-imidazo [5,5-b] pyridine hydrochloride

Prepared according to Example 118 from α-methylmercaptobenzoic acid. Melting point: 230-232 ° C.

Example 122 2- [2- (2-methylmercapto-ethoxy) -5-methylmercapto-phenyl] -1H-imidazo-M, 5b-pyridine hydrochloride__ 50 g of S-methyl- [2- (2-methylmercapto-ethoxy) ) -5-methylmercapto / thio-benzoic acid morpholide iodide (obtained by reacting [2- (2-methylmercanto-ethoxy) -5-methylnercapto] -thiobenzoic acid morpholide with methyl iodide in methanol) and 15 g of 2,3- diaminopyridine in 150 ml of glycol is heated 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 precipitated precipitate is filtered off with suction and recrystallized from methanol.

Melting point: 190-191 ° C.

Example 123 2- (2-Methoxy-H-propylmercapto-phenyl) -imidazo [1,5-b] pyridine hydrochloride 47 5 81 2 6

Prepared according to Example 118 from 2-methoxy-4-propylnercapto-benzoic acid morpholide.

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

Example 124 2- (2-Ethoxy-4-propylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to 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 hydrochloride _______

Prepared according to 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 [1,5-b] pyridine hydrochloride _________________.

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

Melting point: 207-208 ° C.

Example 127 2- (4-Methylsulfinyl-phenyl) -1H-imidazo [15b] pyridine 5.9 g of 2- (4-methylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine hydrochloride are dissolved in 100 to 10 ml of glacial acetic acid and add at 10 ° C 2.4 g of 30% hydrogen peroxide. It is then stirred for 3 hours, allowed to stand overnight in the refrigerator and then for 10 hours at laboratory temperature. Adjust to an ammonia content and rinse several times with chloroform. The starting material is separated by column chromatography, the residue is slurried in acetone and the crystals formed are filtered off with suction. Melting point: 240-2Η2 ° <2.

Example 128 2- (2-Ethoxy-5-methylsulfinyl-phenyl) -1H-imidazo [1,5-b] pyridyl.

Prepared according to 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-methyl-mercapto-phenyl] -1H-imidazo [1,5-b] pyridine _______________________

Prepared according to Example 127 from 2- [2- (2-methylmercapto-ethoxy) -5-methylmercapto-phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 189-190 ° C.

Example 130 2- (2-Ethoxy-14-ethylsulfinyl-phenyl) -1H-imidazo [4,5-b] pyridine

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

Melting point: 166-167 ° C.

Example 131 2- (2-Methoxy-t4-propylsulfinyl-phenyl) -1H-imidazo [1,5-b] pyridine

Prepared according to Example 127 from 2- (2-methoxy- [4-propylmercapto-phenyl) -1H-imidazo [M] -5-b] pyridine hydrochloride.

Melting point: 182-183 ° C.

Example 132 2- (2-Ethoxy-U-propylsulfinyl-phenyl) -1H-imidazo [14,5-b] pyridine Prepared according to Example 127 with 2- (2-ethoxy-1-propyl-mercapto-49,581,2-phenyl) - III-imidazo / 4,5-b / pyridine hydrochloride.

Melting point: 182-183 ° C (Thai).

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

Prepared according to Example 137 from 2- (2-ethoxy-4-butylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride.

Melting point: 185-186 ° C.

Example 134 10 * 2- (4-Methylsulfonyl-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride _____________ 6.95 g of 2- (4-methylmercapto-phenyl) -1H-imidazo [4], Dissolve 5-b / pyridine hydrochloride in 100 ml of glacial acetic acid, add 8.5 g of 30% hydrogen peroxide and keep for 4 days at room temperature. After purification on a silica gel column, the residue is dissolved in acetone and the hydrochloride is precipitated with methanolic hydrochloric acid. Melting point: 286 ° C,

Example 135 2- (2-Ethoxy-4-ethylsulfonyl-phenyl) -1H-imidazo [4,5-b] pyridine 400 mg 2- (2-ethoxy-4-ethylnercapto-phenyl) -1H-imidazo [4,5] -b / pyridine hydrochloride and 0.5 ml of 30% hydrogen peroxide are dissolved in 30 ml of glacial acetic acid, allowed to stand overnight and then heated at 90 ° C for one hour. After cooling, it is diluted with water, neutralized with bicarbonate, extracted with chloroform and the organic phase is evaporated after drying. The residue is purified by column chromatography.

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

Example 136 2- (2-Methoxy-4-propylsulfonyl-phenyl) -1H-imidazo [4,5-b] pyridine Prepared according to Example 135 2- (2-netoxy-4-propylmercapto 58126 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 according to 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 dihydrochloride a) 2- (2-methoxy-4- (2- chloroethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride 14 g of 2-methoxy-4- (2-hydroxyethoxy) -benzoic acid morpholide and 7.1 g of 2,3-diaminopyridine in 100 ml phosphorus oxychloride is heated at reflux for 1.5 hours. It is then evaporated off with ice water, the gradually crystallizing precipitate is filtered off with suction and washed with acetone. Melting point: 266-268 ° C (decomposes).

b) 2 g of 2- (2-methoxy-4- (2-chloroethoxy) phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride and 5 g of dimethylamine in 100 ml of ethanol are heated in a bomb for 12 hours 120 ° C. After evaporation, the residue is purified by column chromatography. The hydrochloride is mixed with acetone and net hydrochloric acid and then recrystallized from methanol.

Melting point: 50250ο0.

Example 139 2-12-Methoxy-4- (3-dimethylamino-propoxy) -phenyl] -1H-imidazo [4,5-b] pyridine dihydrochloride_

Prepared according to Example 138 from 2- [2-methoxy-4- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride.

Melting point: 238-242 ° C.

Example 140 51 58126 2- (2-Methoxy-4- (3-diethylamino-propoxy) -phenyl] -1H-imidazo [4,5-b] pyridine] -dihydrochloride_

Prepared according to Example 138 from 2- [2-methoxy-4- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 222-224 ° C.

Example 141 2- (2-Methoxy-4- (3-piperidinopropoxy) phenyl) -1H-imidazo [4,5-b] pyridine dihydrochloride

Prepared according to Example 138 from 2- [2-methoxy-4- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride. Melting point: 225-226 ° C (decomposes).

Example 142 2- [2-Methoxy-4- (3- (4-phenyl-piperazin-1-yl) -propoxy) -phenyl] -1H-imidazo [4,5-b] pyridyl] -dihydrochloride_

Prepared according to Example 138 from 2- [2-methoxy-4- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride.

Melting point: 197-200 ° C.

Example 143 2- [2-Methoxy-4- (3- (4- (2-methoxyphenyl) -piperazin-1-yl) -propoxy) -phenyl] -1H-imidazo [4,5-b] pyridine] tri- hydrochloride hydraatti_

Prepared according to Example 138 from 2- [2-methoxy-4- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride.

Melting point: Sinteres from 180 ° C.

Example 144 52 5 8 1 26 2- (2-Methoxy-4-morpholino-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride (a) 2- (2-methoxy-4-morpholino-phenyl) - 1,3-Dithiolane iodide 10.5 g of 3-morpholinoanisole and 15.7 g of 2-methylmercapto-1,3-dithiolane methosulphate are boiled in situ in a mixture of 60 ml of glacial acetic acid and 8.3 ml of pyridine. After cooling, it is poured into saturated potassium iodide solution. The red precipitate is filtered off with suction, washed with water and worked up without 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 evaporation, the residue is purified by column chromatography and the hydrochloride is precipitated from acetone with ether / hydrochloric acid. Melting point: 207-209 ° C (decomposes).

Example 145 2- [2-Methoxy-4- (4-methyl-piperazin-1-yl) -phenyl] -1H-imidazo [4,5-b] pyridine dihydrochloride ____

Prepared according to 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 dihydrochloride

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

Melting point: 218-222 ° C.

53 581 26

Example 147 2- [2-Methoxy-4- (4-propyl-piperazin-1-yl) -phenyl] -1H-imidazo [1,5-b] pyridine dihydrochloride________

Prepared according to Example 144 from 3- (4-propyl-piperazin-1-yl) -anisole.

Melting point: 256-258 ° C.

Example 148 2- [2-Ethoxy-4- (4-methyl-piperazin-1-yl) -phenyl] -1H-imidazo [4,5-b] pyridine dihydrochloride _______

Prepared according to 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-1-yl) -phenyl] -1H-imidazo [4,5-b] pyridine dihydrochloride_

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

Melting point: 257-259 ° C.

Example 150 2- [2-Methoxy-4- (4-phenyl-piperazin-1-yl) -phenyl] -1H-imidazo [bis] f

Prepared according to 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-5,812,6

Prepare 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 recrystallizing from isopropanol.

Melting point: 188-190 ° C.

Example 152 2- [4-Methoxy-2- (3- (α-phenyl-piperazin-1-yl) -propoxy) -phenyl] -1H-imidazo [1,5-b] pyridine ___ 10 g of 2- (4-methoxy- 2- (3-Chloropropoxy) -phenyl-1H-imidazo [5,5] pyridine, 10.2 g of 1-phenyl-piperazine and 5 g of potassium carbonate are heated at reflux for 8 hours in 100 ml of ethanol. After ethanol was distilled off in vacuo, recrystallized from ethanol / water 3: 1.

Melting point: 162-163 ° C.

Example 153 2- [α-Methoxy-2- (3- (2-phenyl-ethylamino) -propoxy) -phenyl] -1H-imidazo [1,5-b] pyridine dihydrochloride_

Prepared using 1.77 g of 2- [4-methoxy-2- (3-chloropropoxy) -phenyl] -1H-imidazo [1,5-b] pyridine and heating 2-phenylethylamine for 1 1/2 hours. At 0 ° C, the free base is converted into the dihydrochloride with methanolic hydrochloric acid. Recrystallize from isopropanol.

Melting point: 238 ° C.

Example 154 2 - [+ + - Methoxy-2- (3- (N-methyl-N-2-phenylethylamino) -propoxy) -phenyl-LiZ-1H-imidazo [5,5] pyridine dihydrochloride___ 3.2 g of 2- (2-methoxy-2- (3-chloropropoxy) phenyl) -imidazo [5,5-b] pyridine and 2.7 g of H-methyl-2-phenylethylamine are heated 6 hours in ethanol in a bomb at 120 ° C. The dihydrochloride is precipitated with ethereal hydrochloric acid from a solution of the free base purified by column chromatography in ethyl acetate and recrystallized from isopropanol.

Melting point: 212-215 ° C,

Example 155 2- [4-Methoxy-5- (3- (N-methyl-N- (2- (3,4-dimethoxyphenyl) ethyl) propoxy) phenyl) -1-imidazine 4,5-b) Pyridine dihydrochloride 5.0 g of 2- (4-ethoxy-2- (3-chloropropoxy) phenyl) -1H-indidazo [4,5-b] pyridine and 8.5 g of M- (2 - (3,4-Dimethoxy-phenyl) -ethyl] -methylamine is heated at reflux for 12 hours in ethylene glycol monomethyl ether and the dihydrochloride is precipitated from ethyl acetate with ethereal hydrochloric acid.

• mr '_

Melting point: 159 C.

Example 156 2- [4-Methoxy-2- (3-thiomorpholino-propoxy) -phenyl] -1H-indidazo [4,5-b] pyridine_

Prepared according to Example 158 from 2- (4-methoxy-2- (3-chloropropoxy) phenyl) -1H-imidazo [4,5-b] pyridine and thiomorpholine by heating for 30 hours. For purification, the malenate is precipitated from ethyl acetate 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 3.0 g 2- -methoxy-2- (2-chloroethoxy) -phenyl--1K-indidazo [4,5-b] pyridine and 2.0 g of N-methylpiperazine are refluxed for 40 hours in ethanol. Treat by column chromatography on silica gel and then recrystallize from water.

Melting point: 136-137 ° C.

Example 158 2- [4-Methoxy-2- (3- (4- (2-phenylmethyl) -piperazin-1-yl) -propoxy) -phenyl] -1H-imidazo [4], 5-b / pyridine trihydrochloride 56,581 26

Prepared according to Example 154 from 2- [4-methoxy-2- (3-chloropropoxy) phenyl] -1H-imidazo [4,5-b] pyridine and 1- (2-phenylethyl) piperazine.

Melting point: 236-238 ° C.

Example 159 2- (4-Methoxy-2- (3-methylamino-propoxy) -phenyl] -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 154 from 2- [4-netoxy-2- (3-chloropropoxy) 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 dihydrochloride

Prepared according to Example 154 from 2- [4-methoxy-2- (2-chloroethoxy) -phenyl] -1H-imidazo [4,5-b] pyridine and dimethylamine.

Melting point: 240-242 ° C.

Example 161 2- (2-Methylamino-phenyl) -1H-imidazo [4,5-b] pyridine “1.77 g of N-methylisatoic anhydride and 1.09 g of 2,3-diaminopyridine are melted together and heated for 10 minutes 180 ° C. Recrystallize - from ethyl acetate.

Melting point: 262-263 ° C.

Example 162 2- (2,4-Dimethoxy-phenyl) -3- (2-phenylethyl) -3H-imidazo [4,5-b] pyridine _____ 0.17 g of 2- (2-hydroxy-4- methoxy-phenyl) -3- (2-phenylethyl) -3H-imidazo [4,5b] pyridine is dissolved in 7 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 57,581 2 6 methyl iodide. After 1 hour, water is added, the precipitated product is taken up in ethyl acetate, the organic phase is washed with 2N sodium hydroxide and water and evaporated.

Recrystallize from ethanol / water.

Melting point: 157 ° C.

Example 163 2- (2,4-Dimethoxy-phenyl) -3- [2- (3,4-dimethoxy-phenyl) -ethyl] -3H-imidazo [1,5-b] pyridine hydrochloride

Prepared according to Example 118 from 3-amino-2- [2- (3,4-dimethoxy-phenyl) -ethylamino] -pyridine and 2,4-dimethoxy-benzoic acid. The hydrochloride is precipitated from ether.

Melting point: 195 ° C.

Example 164 2- (2-Fluoro-5-methylmercapto-phenyl) -1H-imidazo [5,4-b] pyridine

Prepared according to Example 118 from 2,3-diaminopyridine and 2-fluoro-5-methylmercapto-benzoic acid.

Melting point: 195 ° C.

Example 165-ν '2- (2-Fluoro-5-methylsulfinyl-phenyl) -1H-imicazo [4,5-b] pyridine

Prepared from 2- (2-fluoro-5-methylmercapto-phenyl) -1H-imidazo [1,5-b] pyridine by oxidation with hydrogen peroxide in glacial acetic acid and at room temperature. Purification is performed by column chromatography on silica gel using 19: 1 chloroform / methanol as eluent. Melting point: 190-192 ° C.

Example 166 2- (2-Fluoro-5-methylsulfonyl-phenyl) -1H-imidazo [1,5-b] pyridine

Prepared from 2- (2-fluoro-5-methylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine as in Example 168 but at 40 ° C.

Melting point: 2ä2 ° C.

Example 167 58 581 26 2- (3,4-Dimethoxyphenyl) -3- (3-morpholinopropyl) -3H-imidazo [4,5-b] pyridine dihydrochloride) a) N- (2-chloro-3- pyridyl) -N '- (3-morpholinopropyl) -3,4-dimethoxybenzamidine 1.9 g of N- (3-morpholinopropyl) -3,4-dimethoxybenzamide and 2.04 g of 2-chloro -3-Aminopyridine is heated at reflux in 85 ml of phosphorus oxychloride for 2 hours. After distilling off the phosphorus oxychloride, it is poured into water, adjusted to alkaline and extracted with ethyl acetate. After evaporation, the compound remains as a viscous __ oil.

b) 2- (3,4-Dimethoxyphenyl) -3- (3-morpholinopropyl) -3H-imidazo [9,5-b] pyridine dihydrochloride ______ 5.2 g N- (2-chloro-3- pyridyl) -N * - (3-morpholinopropyl) -3,4-dimethoxybenzamidine 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 dihydrochloride is precipitated from ether with hydrochloric acid and recrystallized from ethanol / cyclohexane.

Melting point: 180 ° C.

Example 168 - 2- (4-Methoxy-phenyl) -3- (3-morpholeprop-propyl) -3H-indidazo [4,5-b] pyridine dihydrochloride ____

Prepared according to Example 167 from N- (2-chloro-3-pyridyl) -N '- (3-morpholino-propyl) -4-methoxy-benzamidine.

Melting point: 218 ° C.

Example 169 2- (4-Methoxy-phenyl) -3- [3- (4-phenyl-piperazin-1-yl) -propyl] -3H-imidazo [4,5-b] pyridine dihydrochloride hydrate i__

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

Melting point: 100 ° C.

59 5 8 1 26

Example 170 2- (4-Methoxy-phenyl) -3- (2-morpholino-ethyl) -3H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to Example 167 from N- (2-chloro-3-pyridyl) -N '- (2-morpholinoethyl) -4-methoxybenzamidine.

Melting point: 149 ° C.

Example 171 2- (4-Methoxy-phenyl) -3- [3- (4-methyl-piperazin-1-yl) -propyl] -3H-imidazo [4,5-b] pyridine trihydrochloride___

Prepared according to 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 trihydrochloride_

Prepared according to Example 167 from N- (2-chloro-3-pyridyl) -N '- [2- (4-methyl-piperazin-1-yl) -ethyl] -4-methoxy-benzamide. Melting point: 225 ° C.

Example 173 2- (4-Methoxy-phenyl) -3- (3-dimethylamino-propyl) -3H-imidazo [4,5-b] pyridine dihydrochloride__

Prepared according to Example 167 from N- (2-chloro-3-pyridyl) -N '- (3-dimethylaminopropyl) -4-methoxybenzamidine.

Flash point: 229 ° C.

Example 174 2- (4-Methoxy-phenyl) -3- (3-piperidinopropyl) -3H-imidazo [4,5-b] pyridine dihydrochloride____ 60 581 26

Prepared according to Example 167 from N- (2-chloro-3-pyridyl) -N '- (3-piperidinopropyl) -4-methoxybenzamidine.

Melting point: 196 ° C.

Example 175 2- (4-Methoxy-phenyl) -3- (4-morpholino-butyl) -3H-imidazole [4,5-b] pyridine dihydrochloride hydrate_

Prepared according to 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-methyl-mercapto-phenyl) -1H-imidazo [4,5-b] pyridine hydrochloride

Prepared according to 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 according to Example 165 from 2- (2-fluoro-4-methylmercapto-phenyl) -1H-imidazo [4,5-b] pyridine. Crystallize 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 according to Example 167 from N- (2-chloro-3-pyridyl) -N '- (3-morpholino-propyl) -4-methyl-mercapto-benzamidine.

Recrystallize from ether / cyclohexane.

Melting point: 110 ° C.

6i 5 812 6

Example 179 2- [2-Propoxy-4- (4-methyl-piperazin-1-yl) -phenyl] -1H-imidazo [4,5-b] pyridine dihydrochloride

Prepared according to Example 144 from 3- (4-methyl-piperazin-1-yl) -1-propoxy-benzene.

Melting point: 237-238 ° C.

Claims (1)

A process for the preparation of cardiotonic and antihypertensive 2-phenyl-1H-imidazo-S, 5-b / pyridines of the general formula I are isomers of the general formula Ia represented by the general formula Ia, R 1 -NNA \ sH 2 ** Xlj_ / K a> R 1 Wherein R 1 is a methylamino, dimethylamino, morpholino or piperazine group, wherein the piperazine group in the U-position is substituted by an alkyl group having 1 to 3 carbon atoms or a phenyl group, hydroxy, alkoxy, allyloxy, benzyloxy, an alkyl mercapto, alkylsulfinyl or alkylsulfonyl group having 1 to U carbon atoms in the alkyl group, an alkoxy group having 2 or 3 carbon atoms substituted by a halogen atom, hydroxy, alkoxy, alkylmercapto, alkylsulfinyl, alkylsulfonyl, dialkyl methylamino, piperidino, morpholino, thiomorpholino, N-methylpiperazino, N-phenylpiperazino, N-methoxyphenylpiperazino, N-phenylethyl piperazino, phenylethylamino, N-methyl -tyylifenyylie alkylamino or N-methyldimethoxyphenylethylamino, wherein the alkyl groups containing 1 or 2 carbon atoms are hydrogen, fluorine or chlorine, methyl, hydroxy, methoxy, ethoxy, propoxy, methylmercapto, methylsulfinyl or methylsulfonyl group, is a hydrogen atom, a hydroxy or methoxy group, or 2 of the groups R 1 -R 4 together form a methylenedioxy group, R 1 is a hydrogen atom, an alkyl group having 2-U carbon atoms substituted by dimethylamino, piperidino, morpholino, N- methyl-piperazino, N-phenyl-piperazino, N-phenylethyl or N-dimethoxyphenylethyl group, and 63 5 81 26 has a hydrogen or chlorine atom or a methyl group, and their physiologically acceptable acid addition salts with inorganic or organic acids, known in the art. that a pyridine of the general formula II, wherein R 1 is the same as above and Y is a halogen atom or a R 1 NH group in which R 1 is the same as above, is reacted with the formula ra with a compound X-2 (IE) 3 in which R1-R2 are as defined above, and X is a carboxyl group or a functional derivative thereof, and, if desired, a compound of general formula I or Ia thus obtained which contains a reactive halogen atom is converted into an amine and / or the compound of general formula I or Ia thus obtained, which contains a reactive hydrogen atom, is alkylated in the presence of a base with an alkylating agent, and / or the compound of formula I or Ia thus obtained having an alkyl mercapto group or an alkoxy group, having 2 to 3 carbon atoms and substituted by an alkyl rercapto group and / or K 1 is a methyl mercapto group, is oxidized to the corresponding sulfinyl or sulfonyl compound, and / or the compound of formula I or Ia is converted by oxidation to the corresponding HN-oxide, and / or the obtained compound is converted into a physiologically acceptable acid addition salt by means of an inorganic or organic acid. 61ι 58126 For example, 2-phenyl-1H-imidazo [U, 5-b] pyridine is a compound of the formula I and a mixture of methylamino, dimethylamino, dimethylamino piperazino group, color Piperazine group in the U group is substituted with an alkyl group of 1-3 colaters or a phenyl group with hydroxy, alkoxy, allyloxy, benzyloxy, alkylmercapto, al-alkylsulfinyl or alkylsulfonyl group, color alkyl groups ¾ cholatom, an alkoxy group having 2 or 3 cholatom, which is substituted by a halogen atom, a hydroxy, alkoxy, alkylmercapto, alkylsulfinyl, alkylsulfonyl, dialkylaminomethylamino, piperidino, morpholino, thiomorpholino, N- methylpiperazino, N-phenylpiperazino, N-methoxyphenylpiperazino, N-phenylethylpiperazino, phenylethylamino, N-methyl-phenylethylamino or N-methyldimethoxyphenethylamino, colored alkyl groups 1 or 2 -, flu or- or cholatom, en methyl-, hydroxy-, methoxy-, ethoxy-, propoxy-, methylmercapto-, methylsulfinyl or methylsulfonyl group, R ^ avser en väteatom, en hydroxy or methoxy group or 2 av group R ^ -R ^ bildar tillsammans en methylenedioxy, alkyl, hydrogen, alkyl having 2-urol substituents substituted by dimethylamino, piperidino, morpholino, N-methylpiperazino, N-phenylpiperazino, N-phenylethyl or N-dimethoxyphenyl -ethyl group and R ^ avser en väte- or chlorine atom or en methyl group and derivative physiologically acceptable syradium partitioners with organic or organic syrup, känneteck-n at därav, att en pyridin enligt den allmänna formuleln II