DE1420080C - N-Benzyl-beta- (isonicotinoylhydrazine) propionic acid amide and process for its preparation - Google Patents

Description

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The invention relates to N-benzyl - /? - (isonicotinoylhydrazine) propionic acid amide of the formula

N -CO-NH-NH-CH ₂ -Ch ₂ -CO-NH-CH, - '

and a method for its production. 5 by simply mixing the reaction

The method according to the invention consists in allowing participants to stand for about 1 to 3 days

man / i-OsonicotinoylhydrazineJ-propionic acid methyl of the mixture can be achieved at room temperature

ester by methods known per se with benzyl can, one generally draws for the abbreviation of

ainin implements. Response time Temperatures from about 60 to 200 "C

The N-Benzyl '/ J-iisonicotinoylhydrazitO-propion- ίο before. At reaction temperatures of about 130C

Acid aniide can also be prepared by aiming for excellent yields in 2 to 4 hours.

one N-benzyl-ß-hydrazine propionic acid amide with iso- In general, the reaction parts are in

nicotinic acid or its derivatives acylated, or an equimolar amount used, although with advantage

Hydra / .on of the general formula also small excesses of up to 10 ° / ₀ Uen / .yl-

i> n \ Mn μ _ m \ m \ ^{r-rnviuoi 1} S amine or N-benzyl - ^ - hydrazine propionic acid amide an-

Iv Lv / - [N ΓΙ - - IN - Lit - ~ - LMj LvJ INrltv. · <■ .-. τ \ - \ r ι ·· η

* can be turned. The use of larger ones

in which R is the isonicotinoyl ^{radical and R 1 is} the benzyl radical, excess causes no noticeable advantage. So-

means hydrogenated, or isonicotinoylhydrazine with soon the reaction is over, the reaction

an acrylic acid derivative of the general formula mixture cooled and from a solvent, for. B.

CH ₂ -CH - COR ² converts, in the R * - OH, ²⁰ ethyl acetate, lower alcohols such as methanol,

--OCH ₃ , -OC ₂ H ₅ or - NiIR ¹ denotes, ethanol or propanol being recrystallized.

R ¹ in turn denotes the benzyl group, and, if the / J- (isonicotinoyl-

R ⁸ does not mean --NHR ¹ , the compound obtained is hydrazine) propionic acid methyl ester by conversion

diing reacts with benzylamine. Settlement of isonicotinoylhydrazine with a given

The N-benzyl - /? - (isonicotinoylhydrazine) -propion- »5 if present as a diacetal carbonyl compound Acid amide can then with acids with one of the formula O = CH - CH, - COOH or their pK \ value up to 3 in pharmacologically suitable halides, esters, etc. and subsequent ReSalts be transferred. production of the hydrazone obtained accessible.

The N-Benzyl- / i- (isonicotinoylhydrazine) -propion- For the production of the N-Benzyl- / 9- (isonicotinoylhy-

acid amide is suitable for the treatment of psychic 3 ° drazin) propionic acid amide by hydrogenating the

Disturbances and is in much lower doses corresponding hydrazone, the latter is preferred

effective as the well-known sedative Iproni- wise in an ethanolic solution at a pressure of

azide (N-isonicotinoyl-N'-isopropylhydrazine). In the standard 3 atmospheres in the presence of platinum oxide with

dard reserpine antagonism test in rodents de-hydrogen treated.

spoke IO mg N-Benzyl - /? - (isonicotinoylhydrazine) - 35 The implementation of isonicotinoylhydrazine with

propionic acid amide 100 mg jproniazid. Clinical taking an acrylic acid derivative is done by heating one

Studies have also shown that the administration of a mixture of at least equimolar amounts of the

side effects feared by iproniazid, both reaction participants in an inert organic

namely, hepatic toxicity, visual disturbances, and niche solvents, advantageously in the presence of a

strong negative pressure in the case of N-benzyl- / 3- (isonicotinoyl- 40 lower alkanecarboxylic acid, which is generally found in

hydrazine) propionic acid amide does not occur. Its catalytic amounts are used. The amounts

Side effects are minor and temporary. this acid should, based on the entire reaction

The N-benzyl - /? - (isonicotinoylhydrazine) propionation mixture must be at least 1 percent by volume, acid amide also has tuberculostatic and die. optimal amount of alkanecarboxylic acid is in antispasmodic effect, relieves anginal pain 45 generally between 1 and 5 percent by volume of the remainder and lifts the frame of mind from rheumatic action mixture. Those suffering from arthritis can get larger amounts. Also reduce as monoamine oxidase prey. Although preferably acetic acid Inhibitor, especially in the central nervous system, it is used as a catalyst, others can also effective. lower alkanecarboxylic acids, such as formic, propionic

For therapeutic use, it can be used in the usual 50 or butyric acid.
In orally and parenterally administrable dosage forms can be converted into inert organic solvents for this reshaping, in which case tertiary alcohols, in particular, are suitable, and water-solubility of the salts is advantageously used. For salt formation z. B. 1,1-DimethylpropanoI, 1,1-dimethylbutanol, pharmacologically acceptable acids with 1-methyl-1-ethylbutanol and 1,1-dimethylpentanol are suitable. a pKx of 3 or less, e.g. B. Hydrochloric acid 55 The mixture is expediently heated to the reflux hydrochloric acid, sulfuric acid, nitric acid, temperature of the solvent, but phosphoric acid, benzenesulfonic acid, toluenesulfonic acid, and lower temperatures of, for example, SO ⁰ C an-methylsulfonic acid and ethylsulfonic acid. be turned. The implementation is in a short time,

The implementation of the // - (isonicotinoylhydrazine) -pro- after about 6 hours, completed, however, can

pionic acid methyl ester with benzylamine or des 60 can also be carried out over 18 hours. In many

N-βcn / yl / miydrazine propionic acid amide with Isonico cases turned out to be the use of an excess

tinsaurc or its derivatives becomes acrylic acid or its derivatives at temperatures of up to 40%

up to about 200 ° C., if appropriate in the presence of it, as advantageous. After the reaction has ended,

an inert organic solvent, durchge- the product by conventional methods, for. B. by

leads. During the acylation of N-ben / yl - // - hydra / in 65 concentration, crystallization and filtration, worked up,

propionsiiureamids with an Isonicotinsäurehalo- It can be obtained by recrystallization from z. B. lower

Genid is the presence of a hydrogen halide Mkanolen such as methanol, ethanol, prupanol, off

ak / eptors / wcckniältig. Although the reaction is ethyl acetate or acetone purified.

The following examples illustrate the preparation of the compound according to the invention.

Example 1

7.5 g (0.034 mol) of / - (Isonicotinoylhydrazin) -propionic acid methyl ester and 5 cc of benzylamine was slurried and heated with stirring for 3 hours at 130 ⁰ C. It was then cooled and recrystallized from ethyl acetate. White needles of N-benzyl - /? - (isonicotinoylhydrazine) propionic acid amide with a melting point of 151.1 to 152.1 ° C. were obtained in this way.

Analysis for C ₁₆ H ₁₈ N ₁ O:

Calculated: ... C = 64.43, H ----- 6.07, N - 18.77%; found: ... C = 64.43, H = 6.27, N = 10.17%.

B e i s ρ i e 1 2

28.0 g (0.4 mol) of methyl acrylate was added dropwise to a solution over an hour

10 of 54.8 g (0.4 mol) of uonicotinoylhydrazine and 10 ecm of glacial acetic acid in 400 ecm of tert. given üutyl alcohol. It was then heated on a steam bath for 18 hours. Concentration of the reaction mixture to 100 ecm gave 13.0 g of unreacted isonicotinoylhydrazine. The filtrate was evaporated to a thick syrup which was triturated with anhydrous ether and recrystallized from isopropyl alcohol. This gave / J-isonicotinoylhydra / in-propionic acid methyl ester with a melting point of 87 to 88.5 ° C.

Analysis for C ₁₀ H _U H _; N - ■ 5, 87%; Calculated : ... C = N 5, 65%. found· C- .O ₃ : = 53.81, = 54.08,

Reaction of this ester with benzylamine following the procedure of Example I gave N-benzyltf- (isonicotinoylhydrazine) propinic acidic acid.

The same compound was also obtained by hydrogenating the isonicotinoyl hydrazone of N-benzylformyl acetic acid amide or by reacting isonicotinoylhydrazine with N-benzyl acrylic acid amide.

Claims (2)

Claims: 1. N-Benzyl - /? - (isonicotinoylhydrazine) propionic acid amide of the formula N '" ■ CO-NH-NH-CHj-CHj-CO-NH-CH ₂ -; 2. A process for the preparation of N-benzyl- ß- (isonicotinoylhydrazine) propionic acid amide, characterized in that one reacts / HIsonicotinoylhydrazine) propionic acid methyl ester by methods known per se with benzylamine.