DE1670212A1 - Process for the preparation of 3- (5-nitrofuryl-2) -s-triazolo [4,3-a] pyridine derivatives - Google Patents

Description

CP Boehringer & Soehne

GmbH
Mannhe in 1458 a

Process for the preparation of 3- (5-Nltrofuryl-2) -s-triazolo [4.3-a1pyrldln-Derivaten

Addition to patent application B 88 700 IVd / 12 ρ

The subject of patent application B 88 700 IVd / 12 ρ is a process for the preparation of s-triazolo [4.3-a] pyridine derivatives of the general formula I '

(D.

in which R is hydrogen, a halogen atom, an alkyl, alkoxy, amino, acylamino, nitro, carboxyl, Means carboxalkyl or carboxamido group,

characterized by dehydration of 5-Nitrofurfurol-pyrldyl- (2) hydrazones of the formula II

(II),

in which R has the meaning given above, or

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Dehydration of 5-nitrofuroyl- (2) -pyridyl- (2) -hydrazides of formula III

(III).

In which R di has the meaning given above,

or nitration of 3- [puryl- (2)] - e-triazolo [4.5-a] pyridine derivatives of the formula IV

(IV),

in which R has the meaning given above,

whereupon , in the event that R denotes an amino group, the desired case is subsequently saponified.

In an embodiment of the method of patent application B 88 700 IVd / 12 ρ it has now been found that the substances of the formula I can also be prepared by heating amidrazones of the general type Formula V

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in which R has the meaning given above,

optionally in the presence of ammonia-releasing agents, and, if appropriate, by subsequent conversion of the carboxyl group into the carboxyalkyl, carboxamido, amino or acylaralno group.

As an ammonia-releasing agent for the cyclization of the amidrazones V acids, acid anhydrides and acid halides are particularly suitable; however, by simply heating the compounds V reach substances 1 in high-boiling inert solvents «

The NachιUpIiehe conversion of the carboxyl group into the carboxyalkyl or Cnrboxamido group is carried out according to known esterification and aniidation methodone, for example by reacting the corresponding acid halide with lower alcohols or ammonia. Furthermore, one can use the substances I in which "R is a carboxyl group is subject to a customary acid degradation proceeding via the isocyanates (for example by heating the acid azides after Curtius), depending on the solvent used (inert solvent or acids or acyl anhydride) to the amino or Aoy! Amino compounds.

The present invention accordingly relates to these additional ones Variants of the manufacturing processes mentioned in the parent application.

./. BATH ORIGINAL

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example 1

3- [5-N-trofuryl- (2) 1-s-trlazolo [4,3-a1-pyridine

14.1 g of pyridyl (2) -nltrofuramidrazone hydrochloride are heated to the boil with 6 ml of acetic anhydride. After cooling, the product is filtered off with suction and washed with acetic anhydride and ether. Yield: 6.0 g (52 % of theory) of yellow crystals of pp. 276 °. <

The same product can be obtained by boiling the amidrazone resp. its hydrochloride in 2N hydrochloric acid, 50% acetic acid, Aoet = anhydride or nitrobenzene.

The pyridyl (2) nitrofuramidrazone hydrochloride used as starting material is prepared in the following manner: The solution of 10.9 S 2-hydrazine pyridine in 50 ml is added to a suspension of 22.0 g of ethyl nitrofuran iminocarboxylic acid in 100 ml of methanol Given methanol. The mixture is left to stand for 3 hours at room temperature, filtered off with suction, rewashed with methanol and 27.7 g (98 % of theory) of red crystals of mp 231-232 ° (decomp.) Are obtained.

Example 2

Methyl 3- [5-trofuryl- (2) 1-s-triazolo [4,3-a] pyridine-6-carboxylate

13 * 5 g of 3- [5-nitrofuryl- (2)] -s-triazolo [4,3-a] pyridine-6-carboxylic acid are refluxed with 150 ml of thionyl chloride for 8 hours. The reaction mixture is brought to dryness in vacuo, the residue is suspended in benzene and 100 ml of methanol are then added. The mixture is stirred at 55 ° for 1 hour, filtered off with suction after cooling, the residue is neutralized with sodium acetate solution and washed first with plenty of water and then with methanol. Yield: 8.8 g (61 % of theory) of yellow crystals, pp 208-209 °.

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Example 3

3- [5-Nitrofuryl- (2)] - s-triazolo [4,3-a3-pyridine-6-carboxamide

13.5 g of 3- [5-nitrofuryl- (2)] - s-triazolo [4,3-a] pyr ± din-6-carboxylic acid are as described in Example 2 with thionyl chlorid to the acid chloride implemented and suspended in anhydrous ether. By introducing ammonia gas, the amide is obtained in a yield of 12.8 g (94 # of theory) * greenish-yellow crystals of pp. 285 ° (decomp.).

Example 4

6-Amino-3- [5-nitrofuryl- (2) 3-s-triazolo [4,3-a) pyridine 2.7 g of 3- [5-nitrofuryl- (2)] - s-triazolo [4.3 -a] pyridine-6-carboxylic acid are converted into the acid chloride as described in Example 2. The residue is suspended in 100 ml of acetone and a solution of 0.68 g of sodium azide in 1.7 ml of water is added with stirring. The precipitate, which consists of highly contaminated acid azide, is filtered off with suction. The filtrate is mixed with water and 1.7 g (57 % of theory) of 3-C5-nitrofuryl- (2)] - s-triazolo [4,3-a] pyridine-6-carboxylic acid azide, yellow crystals, are obtained from pp. 14o-1445 ° (decomp.). 1.50 g of the 3- [5-nitrofuryl- (2)] - s-triazolo [4,3-a] pyridine-6-carboxylic acid azide obtained in this way are heated in a mixture of dioxane and water (2: 1) until the evolution of nitrogen stops 1st. The reaction mixture is brought to dryness in vacuo, the residue is extracted with sodium bicarbonate solution, dissolved in 2N hydrochloric acid and reprecipitated by neutralization, yield 0.12 g (10 % of theory) of red crystals which turn dark from 270 ° and from 2δΟ ° color black without melting. -

In an analogous manner, by heating the carboxylic acid azide in acetic anhydride, 6-acetamino-3- [5-nitrofuryl- (2)] - s-triazolo- [4,3-a] pyrldine is obtained in the form of greenish-yellow crystals, which turn brown from 270 ° and decompose at 310 °.

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Claims (1)

Claim Process for the preparation of s of the general formula I. in the E hydrogen; a halogen atom, an alkyl, -Alkoxy- * Amino «, _ acylamino-, nitro-, carboxyl-, Carboxalkjfl »or O & rlöoxamlQgruppe means characterized in that in an embodiment of the method der Hau ^ tanmelöang B 88 700 IVd / 12 ρ either Amidrasone of the general in -der H has the meaning given above, optionally heated in the presence of ammonia-releasing agents or the compound obtained by any process variant in which R means the carboxyl group, subsequently into the carboxy » alkyl, carboxamido, amino or acylamino derivatives.