DE1062245B - Process for the preparation of 2-amino-4-pyridyl- (2 ') -thiazole and its salts - Google Patents

Description

Process for the preparation of 2-amino-4-pyridyl- (2 ') -thiazole and its salts The invention relates to processes for the preparation of 2-amino-4-pyridyl- (2') -thiazole of the formula \ N / N ' \ NH 2 and its salts.

The new compound and its salts have good analgesic properties and are antipyretic. Accordingly, they can be used as a medicine. Testing the analgesia in the mouse, measured by the extension of the reaction time when exposed to a thermal stimulus at the tip of the tail, results in the 2,4- known from Helvetica Chimica Acta, Vol. 38 [19551, pp. 1289 to 1291, Bis- (a-pyridyl) -thiazole at a dose of 500 mg / kg orally has no effect, while 2-amino-4-pvridyl- (2 ') -thiazole with low toxicity already has an effect at a dose of 250 mg / kg orally Showing 63 % increase in response time.

The also known 2-amino-4-phenyl-5-methylthiazole has no analgesic effect on the basis of the information in "Bulletin de la societe chimique de France", 5th series, Vol. 17 [ 1950], p. 582 and is very toxic to mice.

The new compound is obtained in a manner known per se. A Procedure consists e.g. B. in that you have 2-acetylpyridine, the one in the acetyl radical reactive substituents, e.g. B. the diazo group, or a reactive one esterified oxy group, preferably 2-haloacetylpyridine with thiourea implements. For example, 2-chloroacetylpyridine can be reacted with thiourea.

Another embodiment of the method is that one 2-acetylpyridine with thiourea and oxidizing agents, e.g. B. iodine can react.

Depending on the working method, the new connection is obtained in the form of the free base or its salts. From the salts can in a manner known per se free base can be obtained. The latter can be converted into acids, which are suitable for the formation of therapeutically useful salts, extract salts, z. B. those of the hydrohalic acids, sulfuric acid, nitric acid, phosphoric acid, Rhodanic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, Malic acid, methanesulphonic acid, ethanesulphonic acid, oxyethanesulphonic acid, benzene or Toluenesulfonic acid or of therapeutically effective acids per se.

The new compound or its salts can be mixed with one for pharmaceutical, enteral, parenteral or topical application organic or inorganic, solid or liquid carrier material as a medicament Find use. The starting materials used according to the process are known or can be obtained by methods known per se. You can also use the Reaction conditions are obtained.

The invention is described in more detail in the following examples.

Example 1 3 g of crude 2-chloroacetylpyridine in 50 cm3 of absolute ethanol are refluxed with 5 g of thiourea for 10 hours. Then the Alcohol is distilled off and the residue is heated to 150 ° C. for a further 90 minutes. The reaction mixture is taken up in 50 cm3 of 4N hydrochloric acid, extracted three times with 50 cm3 of ether each time, to remove by-products, the aqueous phase with saturated sodium bicarbonate solution made alkaline and shaken out three times with 100 cm3 of ether each time. The dark brown one crystalline ether residue is extracted five times with 40 cm3 hot ligroin each time. When the ligroin cools down, colorless crystals separate out, which twice more be recrystallized from ligroin. The 2-amino-4-pyridyl- (2 ') -thiazole is obtained in this way, F. 175 to 176 ° C (yellow color).

Example 2 10 g of 2-acetylpyridine, 19 g of iodine and 12.8 g of finely ground Thiourea are in 50 cm3 carbon tetrachloride for 16 hours on a water bath heated, whereby the mixture discolored. Then the carbon tetrachloride evaporated in vacuo. The raw hydroiodide is made three times with the addition of animal charcoal from ever 150 cm3 of water recrystallized. Then in hot Dissolved water, made the solution alkaline with concentrated ammonia solution, that precipitated free amine is filtered off and recrystallized from ligroin after drying. Colorless crystals of 2-amino-4-pyridyl- (2 ') - thiazole are obtained, which at 172 to Melting at 174 ° C.

Claims (3)

PATENT CLAIMS: 1. Process for the preparation of 2-amino-4-pyridyl- (2 ') -thiazole and its salts, characterized in that 2-acetylpyridine, which is in the acetyl radical carries a reactive substituent, preferably 2-haloacetylpyridine, with thiourea or that 2-acetylpyridine is reacted with thiourea and oxidizing agents converts and optionally converts the compounds obtained into their salts. 2. The method according to claim 1, characterized in that 2-chloroacetylpyridine and Thiourea can be used as starting compounds. 3. The method according to claim 1, characterized in that 2-acetylpyridine, thiourea and iodine are used as starting compounds. References considered: U.S. Patent No. 2,481,674; Helvetica Chimica Acta, 38: 1289-1291 [1955]; Bulletin de la societe chimique de France, 5th series, vol. 17 [1950], p. 5 8 2.