DE1795544A1 - METHOD FOR PRODUCING PHENYLAMINO-PYRIDINES - Google Patents

Description

Process for the production of phenylamino-pyridines Ausseheidullg from patent (application P 14 45 673.6-D 45302) The invention relates to a process for the production of new compounds of the general formula I. where ltj is hydrogen, an amino group or an alkylamino group and the radicals n2 and R3 are identical or different and are halogen atoms, trifluoromethyl groups, low molecular weight alkoxy groups, hydroxyl groups, carboxy groups or amino groups and their salts.

The new compounds have valuable pharmacological properties. They are characterized by a high anti-inflammatory effect.

The compounds according to the invention are prepared by reacting in a manner known per se in a compound of the general formula II where R1, R2 and R3 have the meanings given overleaf, and can also be nitro groups, this nitro group (s) reduced by known methods, preferably in the presence of a catalyst, for example flaney nickel.

It is advisable to hydrogenate the nitro groups at around 70 ° C and to be carried out at a pressure of about 20 to 30 atmospheres.

In addition to llaney nickel, the following catalysts can also be used: Palladium black or palladium or palladium hydroxide on a carrier material such as barium sulfate or calcium carbonate. The reduction can also be carried out with zinc / hydrochloric acid, tin / hydrochloric acid, Tin (II) chloride / hydrochloric acid or iron / hydrochloric acid or salts of hydrogen sulfide in alcohol / water at about 700 to about 1200 C or with activated aluminum in water-containing ether at 200 to 40 ° C.

The compounds according to the invention can be used in a manner known per se be converted into the salts.

Example 1 2- (3-Trifluoromethylphenylamino) -5-aminopyridine 142 g of 2- (3-trifluoromethylphenylamino) -5-nitro-pyridine are hydrogenated in 600 ml of methanol in the presence of 30 g of Raney nickel at 700 ° C. and 20 to 30 atmospheres. After the solvent has evaporated, the residue is distilled in vacuo. The base goes over at 0.5 torr at 190 to 1920.degree. It forms a crystalline salt with maleic acid, which melts at 115 ° C after recrystallization from isopropanol.

Example 2 2- (4-pentylexyphenylamino) -5-aminopyridine 2- (4-Pentyloxyphenylamino) -5-nitro-pyridine is hydrogenated with Raney nickel and worked up analogously to Example i. The base boils at 0.5 torr between 225 and 2350 C.

Example 3 2- (4-fluoro-phenylamino) -5-aminopyridine 126 g of 2- (4-fluoro-phenylamino) -5-nitro-pyridine are suspended in 1.2 l of methanol and hydrogenated in the presence of 13 g of Raney nickel at 600 ° C. and 50 atmospheric pressure in an autoclave. After the catalyst has been filtered off with suction, the filtrate is evaporated and the residue is recrystallized from alcohol / gasoline, mp 141 ° C.

Example 4 2- (2-Methyl-5-chlorophenylamino) -5-aminopyridine 2- (2-Methyl-5-chlorophenylamino) -5-nitro-pyridine is reduced as in Example 3. The reaction product is distilled in vacuo.

Bp 0.5: 190-5 ° C; Yield: 92%.

Example 5 2,3-Diamino-6- (3-trifluoromethyl-phenyl-amino) -pyridine 115 g (0.5 mol) of 2-amino-3-nitro-6- (3-trifluoromethyl-phenylamino) -pyridine in 500 ml of dioxane is mixed with 12 g of Pd / activated carbon (10%) with the addition of 60 g of sodium sulfate Hydrogenated at 20 atu and 500C. After suctioning off, add 100 ml of ether and benzine until the onset of cloudiness. The base crystallizes out.

It is quickly sucked off (sensitive to air). Yield: 70 g.

By adding isopropanolic hydrochloric acid to a solution of the amine Ilydroclilorid precipitates in ethanol.

M.p. 30 (30 C (dec.).

Example 6 2,3-Diamino-6- (2,3-dicllloropllenyl) -aminoyridine A solution of 27 g of 2-amino-3-nitro-6- (2,3-dichlorophenyl) aminopyridine in 400 g of dioxane is hydrogenated as in Example 3.

100 ml of 6N isopropanolic are added to the filtered hydrogenation solution HCl. The precipitated salt is filtered off with suction and recrystallized from methanol.

F. 257-90 (z).

Claims (2)

P ate ii claims 1. Process for the preparation of compounds of the general formula I where R1 is hydrogen, an amino group or an alkylamino group and the radicals R2 and R3 are identical or different and mean halogen atoms, trifluoromethyl groups, low molecular weight alkoxy groups, hydroxyl groups, carboxy groups or amino groups, characterized in that in a manner known per se in a compound of the general Formula II in which R1, R2 and R3 have the meanings given above, and also know to be nitro groups, these nitro group (s) are reduced by known methods, preferably in the presence of a catalyst, for example Raney nickel. 2. The method according to claim i, characterized in that the The compounds obtained are converted into the salts. Annex to excretion from P 14 45 673.6-44 (D 45 302) test report The compounds according to the invention were on protein edema of the rat paw after Method by DMENJOZ and colleagues, Arch. Exp. Pharm.Path. 230, 325 (1957) on anti-inflammatory Effect tested. The antipholgistic effect is as opposed to edema inhibition in percent the untreated control group. It was applied orally in all experiments. The dose was always 300 mg / kg rat. The toxicity test was carried out on the mouse orally by determining the acute toxicity (LD 50 mg / kg) according to Miller and Tainter (Proc.Soc.Exper.Biol.and Med. 57, 261 (1944). The observation time was 24 hours. The well-known anti-inflammatory phenylbutazone was used as a comparison substance chosen. The results are given in the table below. Substance protein edema LD 50 mg / kg inhibition in% oral example at 300 mg / kg oral 1 51 1 130 6 40 4 000 phenyl-35 530 butazone