SU535908A3 - Method for preparing imylazo- (4,5-b) -pyridine derivatives - Google Patents

Description

.R

-C-N: R

X.

where X is an oxygen or sulfur atom; one R value is phenyl, lower alkyl (Ci- € 4) or lower alkenyl (C2- € 4), and another R value is hydrogen, lower alkyl (Ci- € 4) or lower alkenyl (€ 2- € 4) iri provided that both radicals K together do not contain more than 6 carbon atoms, or both radicals, taken together, form alkylene (€ 2-Ce) with a direct chain, 4) a radical of the formula

ABOUT

- /

 with f-e - (R 14 where R is methylene, ethylene or vinylene, or 1,

5) a group of the formula -S02-R, where R is lower alkyl, as indicated above, cycloalkyl (Cs-Sb), phenyl or benzyl, or

6) a radical of the formula —CO — X— (lower alkyl of C— € 4) or of the formula

where X is oxygen or sulfur, is treated with chlorine or fluorine-containing and its nucleophilic reagent.

By chlorine or fluorine containing compounds, they are meant both as compounds that themselves serve as a nucleophilic reagent, and as a compound that only include the nucleophilic part, as HC1 includes C1. Typically, the approach is that their nucleophilic reagents are compounds that give a halide ion such as chloride or fluoride. The halide ion can be an ion in a halide acid, it can be an ion in any of the compounds used to produce unstable halides, oxyhalides or thiohalides described above; or it may be a halide ion of oxalyl halide or phosgea. Thus, the nucleophilic reagents used in the proposed method include HCl, HF, lithium chloride, phosphorus oxychloride, phosphorus trichloride, phosphorus oxyfluoride, antimony pentachloride, antimony oxychloride, thionyl chloride, ammonium chloride and ammonium fluoride.

The reaction takes place in an inert solvent used as reaction medium. Suitable solvents are lower alkanols, ethers such as diethyl ether and tetrahydrofuran, hydrocarbons and acetone. If an oxyhalide of the group A or sulfur is used as the nucleophilic reagent, it is preferable to use a small

amount of dimethylformamide. The reaction proceeds at O-150 ° C. In the reaction, 1-hydroxy derivative and nucleophilic reagent are used in equimolar amounts. Separation and, if necessary, purification are carried out by conventional methods.

In some cases, as a result of the reaction, the product is obtained as an imidazole salt of a nucleophilic reagent.

H®

Have

Nk

The salt is easily converted to imidazole by conventional methods. Example 1. Preparation of 6-chloro-2- (trifluoromethyl) -1 H-imidazo (4,5-b) -pyridium.

Dimethylformamide (2 ml) was added to 4 g of 1-hydroxy-2- (trifluoromethyl) -1 H-imidazo (4,5-b) pyridine in 10 ml of thionyl chloride. The resulting reaction mixture is heated on the steam bath overnight. The solvent is removed and the residue is shaken with 50 ml of water and filtered. The residue is then taken up in a hydroxide of sodium, filtered and acidified to pH 3, shaken with three 150 ml portions of diethyl ether and dried with magnesium sulfate. The solvent is evaporated and the desired 6-chloro-2- (trifluoromethyl) -H-imidazo- (4,5-b) -pyridine is thus obtained, and so on. 190-292 ° С, with sublimation from 260 ° С.

Example 2. Preparation of 5,6-dichloro-2- (trifluoromethyl) -1H-imidazole- (4,5-b) -pyridine.

1 - (Methylcarbamoyloxy) -6-chloro-2- (trifluoromethyl) -1H-imidazo- (4,5-b) -pyridine (250 mg) in 2.5 ml of methanol is saturated with HC1. Reactionary

the mixture is allowed to stand for 3 hours, then poured into

water and filtered to separate the desired

5,6-dichloro - 2 - (trifluoromethyl) - III-imidazo (4,5-b) -pyridine. T. pl. 228-230 ° C.

Example 3. Preparation of 5,6-dichloro-2- (trifluoromethyl) - H-imidazo (4,5-b) -pyridine.

1-Oxy-5-chloro -2- (trifluoromethyl) -H-imidazo (4,5-b) -pyridine (00 mg) is mixed with 0 ml of thionyl chloride and the mixture is heated under reflux on a steam bath for 0 The thionyl chloride is then evaporated off and the residue is the desired product, 5,6-dichloro-2- (trifluoromethyl) -H - imidazo- (4,5-b) -pyridine, shaken with water and separated by filtration; m.p. 222-224 ° C.

Example 4. Preparation of α-hydroxy-6-chloro-2 (trifluoromethyl) -H-imidazo (4,5-b) pyridine. 5-Chloro-3-nitro-2- (trifluoroacetamido) -pyridine (2.0 g) is hydrogenated with two mol-equivalents of hydrogen in ethanol, containing 0.5 g

5% palladium on coal. The uus reaction mixture is filtered and evaporated to separate 6-chloro-1-hydroxy-2- (trifluoromethyl) -1 H-imidazo (4,5-b) pyridine, which after recrystallization from benzene, melts at 268-270 ° s

Found,%: C 35.59; H 1.45; IN 17.77.

Calculated,%: C 35.39; H 1.27; N 17.69.

Esters used as starting materials are prepared by known methods.

Most of the derivatives of esters are obtained by the interaction of the corresponding 1-hydroxy compounds of the formula

HE

A j.C. with a halide compound of the formula where X is a halogen, in the presence of an alkali metal carbonate or other hydrogen halide acceptor. An inert liquid reaction medium may be used. The reaction takes place over a wide range of temperatures, but is preferably carried out at temperatures from -20 ° C to reflux temperature. Separation and, if required, purification are carried out by standard methods.

Although this method is the most common method, other methods are acceptable, and they may be preferred for some of the compounds. So, carbamates of the formula

O - C - NH lower alkyl or lower alkenyl is obtained more easily by reacting the corresponding 1-hydroxy compound with isocyanate. The reaction is carried out in the usual manner. Similarly, carboxylic acid ester compounds of the proposed process, other than carbamate esters, are preferably prepared by reacting the desired carboxylic acid as its anhydride with the corresponding 1-hydroxy compound.

Other synthetic methods can also be used in the preparation of the compounds of the present invention. Examples include: use of B, M-carbonyldiimidazole or B, M-dicyclohexylcarbodiimide.

Claims (1)

Invention Formula The method of obtaining imidazo (4,5-b) -pyridine derivatives of formula H -y-I - y 0.1 or 2 Jsl- N nd ,, ri-t (o t-vi-X JVf .-de V - chlorine or fluorine; R is hydrogen, chlorine, fluorine, perfluoroalkyl (Ci-Sb) or a radical of formula where each value of Z is a hydrogen or halogen atom, and p is 0 or 1; each value of R is halogen, nitro, The group of formulas -CHP, -CFsCl, -CFaH or its lower alkyl-sulfonyl (Cj-C4), provided that no more than one value of R6 is a nitro group, -SFZ, -CFaCl, -SrgP or (its lowest alkyl) is a sulfonyl characterized in that the 1-hydroxybenzimidazole or imidazo (4,5-b or c) -pyridine ester of formula 2 O-C hJ aVcF, -E and ... v, 0.1 or 2 N where R1 and RS have the indicated values, and R2 is a group formed by the interaction of the corresponding 1-hydroxy compound with chloride, fluoride, oxychloride, oxyfluoride or oxide of the element V of the main group of the periodic system with an atomic weight of from 30 to 122 inclusive, or sulfur oxide, or R2 - the following radicals: (1) alkanoyl (C2-Cie), 35 (2) alkeioil (Cz-Cie), (3) carbamoyl formula .R -C-N: X where X is an oxygen or sulfur atom, one of the values of R is phenyl, lower alkyl (Ci-C4) or lower alkeiyl (C2-C4), and another value of R is hydrogen, lower alkyl Ci-C4 or the lowest alkenyl, provided that both radicals R together must not contain more than 6 carbon atoms, or both radicals R together form alkyles of normal structure, (4) radical of the formula where W is methylene, ethylene or viylene, and q is 0 or 1, (5) the radical of the group, -SO2-R, where R is lower alkyl, cycloalkyl (Cs-Sb), phenyl or benzyl, or 6) a radical of the formula -CO-X- (lower alkyl Ci-C4) or a radical of the formula where X is an oxygen or sulfur atom, is treated with a chlorine or fluorine-containing compound in an organic solvent medium. The source of information taken into account during exerntize: 1. US Patent No. 3.459.759, cl. 260-296, 1969 (prototy).