DE1140940B - Process for the preparation of N- (p-aminobenzenesulfonyl) -N-acetyl-5-amino-3-methyl-1-phenyl-pyrazole - Google Patents

Description

GERMAN

PATENT OFFICE

C 18536 IVd / 12 ρ

\ N M K I. D E T A G: March 5, 1959

NOTICE
OKR INMELDl ¹ NG
AND ISSUE OF

as a legend: DECEMBER 13, 1962

The invention relates to the preparation of N-ip-aminobenzene sulfony ^ -N-acetyl-S-amino-S-methyl-1-phenyl-pyrazole the formula

H ₂ N

CH ₃

The new compound is obtained if one ei η 5- (Benzolsulfonaniido) -3-methyl-1-phenyl-pyrazole the general formula

Process for the production of the

N- (p-aminobenzenesulfonyl) -N-acetyi-

5-amino-3-methyl-1-phenyl-pyrazoles

'

Applicant:
CIBA Aktiengesellschaft, Basel (Switzerland)

Representative: Dipl.-Ing. E. Splanemann, patent attorney, Hamburg 36, Neuer Wall 10

Claimed priority:
Switzerland of March 14, 1958 (No. 57 048)

C ₆ H ₅

SO ₂ -

HC
I! -C N Il
Λ-Ι
\ N H \ /

CH ₃

Dr. Jean Druey, Riehen.

and Dr. Paul Schmidt, Therwil (Switzerland),

have been named as inventors

in which R denotes the amino group or a radical which can be converted into this by reduction, in an Ni-acylated in a known manner and convertible into the amino group in compounds obtained with a Radical R converts this into the free amino group.

One that can be converted into the amino group by reduction Rest is z. B. the nitro or azo group or an acylamino group cleavable by hydrogenolysis, like the carbobenzoxyamino group. The reduction is carried out in a manner known per se, expediently while avoiding hydrolyzing conditions and higher temperatures, in order to avoid cleavage or rearrangement of the Ni-acetyl radical to the Ni-nitrogen atom. Reduction with hydrogen in the presence of catalysts such as noble metal catalysts is particularly suitable, z. B. Palladium on charcoal.

The Ni acetylation is carried out in the usual way Use of Ni-acetylating agents carried out. Such are especially the acid anhydrides or -halides, such as -chloride. The reaction is expedient in the presence of basic agents, such as inorganic ones or organic bases, e.g. B. alkali carbonates or tertiary amines, such as pyridine, picoline, lutidine, Collidine. Trimethylamine, triethylamine. Tributylamine or 1,6-bis-dimethylamino-hexane, and in the presence inert diluents, especially organic solvents such as dioxane, benzene, toluene, halogenated hydrocarbons, e.g. B. methylene chloride or chloroform, dimethylformamide, lower aliphatic ketones such as acetone or methyl ethyl ketone or optionally the basic ones Means themselves, e.g. B. pyridine or mixtures thereof, such as especially pyridine-acetone. carried out. Advantageous one works in a medium that is as water-free as possible. If an acid halide is used, one can also a metal salt of sulfonamide, e.g. B. use an alkali salt or better the silver salt, This makes the addition of basic agents recommended above unnecessary. Your additional use, z. B. as a diluent, but nothing stands in the way.

When using 5- (p-aminobenzenesulfonamido) -3-methyl-1-phenyl-pyrazole, care must be taken that the reaction is carried out under mild conditions and using approximately equimolecular amounts of the reactants in order to avoid Ni, N4 -Bis-acetyl compound or Ni-acetyl compound is formed by acyl migration. It is therefore advantageous to work at a low temperature, e.g. B. below 40 ⁰ C, such as between 10 and 30 ⁰ C, and in an anhydrous medium. When using the acid halides, it is advisable to start from the metal salts of the sulfonamide, such as the silver salt.

209 747/325

The new compound has valuable chemotherapeutic properties. She has a strong and long-term effect on streptococcal sepsis in mice. This is how it works in a can area from 10 to 50 mg / kg in streptococcal sepsis in mice better than 2,4-dimethoxy-6-sulfonilamido-1,3-diazine and also has a clearly superior long-term effect. She also shows a very good one Activity against coliforms in urine and intestines. In addition, it is practically free from unpleasantness Taste qualities, as they are often attached to sulfonamides, and can therefore be included Serve advantage for making tablets and syrups.

The invention is described in the following example. The temperatures are in degrees Celsius specified.

example

In a flask equipped with a stirrer and thermometer, 16.4 g of 5- (p-aminobenzenesulfonamido) -3-methyl-1-phenyl-pyrazole are dissolved in 40 cm ^{3 of} acetone and 8 cm ^{3 of} dry pyridine. 5.1 g of acetic anhydride are added dropwise with stirring over the course of 5 minutes. The mixture is stirred for 5 hours and the mixture is left to stand for 10 hours. ^{50 cm 3 of} 3% strength aqueous ammonia and a little ice are then added with stirring, after which an oily product precipitates. 400 cm ^{3 of} water are added and the mixture is left to stand for 10 hours at room temperature, the oil formed gradually crystallizing. The N- (p-aminobenzenesulfonyl) -N-acetyl-5-amino-3-methyl-1-phenyl-pyrazole thus obtained is recrystallized from ethanol diluted with water and is thus obtained in white crystals with a melting point of 121 ° to 122 °.

The 5- (p-aminobenzenesulfonamido) -3-methyl-1 used as starting material -phenyl-pyrazole is obtained as follows:

108 g of 96% p-acetylamino-benzenesulphonic acid chloride are introduced into a solution of 70 g of 5-amino-3-methyl-1-phenyl-pyrazole in 350 cm ^{3 of anhydrous pyridine within about 20 minutes.} After the reaction has subsided, the mixture is heated to an internal temperature of 90 to 95 ° for a further hour. The reaction solution is then poured into 1.51 2N hydrochloric acid, the sulfonamide precipitating in a greasy form. After decanting the water, the grease is saponified directly.

The crude product is refluxed in 1.41 2.5 N sodium hydroxide solution for 2 hours. The solution is clarified with animal charcoal and the filtrate is adjusted to pH 5 to 6 with 6η hydrochloric acid, after which a precipitate separates out, which soon solidifies in crystalline form. It is recrystallized from 350 cm ^{3 of} ethanol with the addition of animal charcoal. This gives 5- (p-amino-ο benzenesulfonamido) -3-methyl-1-phenyl-pyrazole in white crystals with a melting point of 181 ° to 182 °.

Claims (1)

PATENT CLAIM: Process for the preparation of N- (p-aminobenzenesulfonyl) -N-acetyl-5-amino-3-methyl-l-phe- nyl-pyrazoles of the formula HC ₄ , C - CH ₃ (41 H ₂ N <11 Il Il -SO ₂ -NC? - ¹ N I \ _N / CO V CH ₃ C ₆ H ₅ characterized in that a 5- (benzenesulfonamido) -3-methyl-1-phenyl-pyrazole of the general formula HC SO ₂ -NC H N C- CH ₃ C ₆ H ₅ where R denotes the amino group or a radical which can be converted into this by reduction, Ni-acetylated in a manner known per se and in compounds obtained with one in the amino group convertible radical R converts this into the free amino group. Documents considered: German Patent No. 952 809; British Patent No. 788 140; HeIv. chim. Acta, 41 [1958], pp. 306-309. 209 747ß2S 12.62