DE1005077B - Process for the preparation of choleretically active N-acyl derivatives of 2,4,6-triiodo-3-aminobenzoic acid - Google Patents

Description

GERMAN

Patent 936,928 describes a process for the preparation of N-acyl derivatives of 2, 4, o-triiodo-S-aminobenzoic acid the general formula

NH.Ζ-Υ
J

COOH

procedure
for making choleretic

effective N-acyl derivatives
of 2,4,6-triiodo-3-aminobenzoic acid

Addendum to patent 936 928

Applicant:

Schering Aktiengesellschaft,
Berlin N 65, Müllerstr. 170-172

described, wherein Z is the acyl radical of a polybasic carboxylic acid and Y is the hydroxyl group or an alkoxy group or an unsubstituted, mono- or disubstituted amide group, including the group

Dr. Hans Priewe, Berlin-Steglitz,
has been named as the inventor

means, and which consists in the fact that one 2, 4, 6-triiodo-3-aminobenzoic acid with the acid halides or with the ester acid halides or with N-substituted ones or N-unsubstituted amide acid halides of polybasic carboxylic acids and, if end products are desired, in which Y is the hydroxyl group, in primarily formed polycarboxylic ester amides the carboxylic ester group contained in the —Z · Y group is saponified.

The process products of the patent 936 928 have therapeutically valuable properties, insofar as for at least some representatives of this group of compounds have a more or less pronounced choleretic effect Effectiveness.

In a further development of the inventive concept of the patent 936 928 it has now been found that said valuable properties do not affect the N-acylated 2, 4, 6-triiodo-3-aminobenzoic acids obtainable by the process of this patent themselves are limited, but are also suitable for their descendants, which are characterized by functional Derive modification of nuclear carboxyl groups from the acids mentioned.

According to the invention, these derivatives correspond to the general formula

NH-Z-Y

CO-R

wherein Y and Z are the same as above and R is an alkoxy group or an unsubstituted, mono- or disubstituted one Means amide group.

The new connections are made

by replacing the free 2, 4, 6-triiodo-3-aminobenzoic acid with their functional derivatives of the general formula

CO-R

wherein R is as defined above, subjected to the above process of patent 936,928.

If end products are desired in which Y is the hydroxyl group, it is the same as in the process of patent 936 928 possible, in primary

609 866/434

which polycarboxylic ester amides saponify the carboxylic ester group contained in the - Z-Y part of the molecule, without at the same time a functionally modified nuclear carboxyl group contained in the molecule part - CO-R is set free again, since the latter is far less reactive due to steric hindrance,

example 1

10.3 g of 2, 4, 6-triiodo-3-aminobenzamide are ¹ in 120 ecm dichlorobenzene heated to 140 °, then about 20 ecm solvent is distilled off under reduced pressure, then at 160 to 165 ° to the clear solution within 10 minutes 4.25 g Adipinsäureäthylesterchlorid added dropwise and stirred for a further 2 ¹ Z ₂ hours at this temperature. The resulting precipitate is filtered off with suction while hot and washed with petroleum ether. Crude yield 6.7 g of adipic acid - ethyl ester - (2, 4, 6 - triiodo-3-carbamido-amlide)

IO For the production of adipic acid mono- (2, 4, 6-triiodo-3-carbamido-anilide)

'V-NH · CO - (CH ₂ ) ₄ -CO-OH

J ^Lj

i
CO-NH,

V-NH-CO- (CHg) ₄ -CO. OC ₂ H ₅

CO-NH

proceed as follows:

3 g of the ester obtained above are passed through with 10 ecm n NaOH. Saponified for 2 hours heating at 60 °. The saponification product is precipitated with dilute hydrochloric acid and recrystallized from methanol. yield 2.5 g (corresponding to 87% of theory)! F. 268 to 273 ° (Decomposition). .

Example 2

2.86 g of 2,4,6-triiodo-3-aminohippuric acid are dissolved in hot water in 1 cm of dry dioxane and mixed with 30 cm of chlorobenzene. Then 0.46 g of adipic acid dichloride, diluted with 5 ecm of chlorobenzene, are added dropwise over the course of 30 minutes with stirring and refluxing. That! Reaction mixture ""' ^J

corresponding to 50% of theory. UmkristaUisiert from methanol F. 269 "to 270 ° (decomp.) 'Heated for a further 4 hours. The granular Reaction product, the adipic acid bis [2,4,6-triiodo-3- (carbamido-N-acetic acid) anilide]

J-

NH --CO (CH ₂ ) ₄ CO NH-

j J-

-J

CO-NH-CH ₉ -COOS CO-NH-CH ₉ -COOH

(Yield 2 g = 64% of theory) is boiled with methanol and treated by multiple treatments of its solution in aqueous sodium bicarbonate with decolorizing carbon, followed by reprecipitation with dilute hydrochloric acid, cleaned. The purified product has no definite melting point. When heated, occurs from 240 ° Decomposition a.

Claims (1)

PATENT CLAIM: Further development of the method according to patent 936 928 for the production of choleretically active N-acyl derivatives of 2,4, o-triiodo-S-aminobenzoic acid the general formula CO-R J-r-J -NH-Z-Y 55 60 acid, Y the hydroxyl group, an alkyloxy group or an unsubstituted, mono- or disubstituted Amide group and R is an alkyloxy group or an unsubstituted, mono- or disubstituted one Amide group means, characterized in that instead of the free 2, 4, o-triiodo-S-aminobenzoic acid their functional derivatives of the general formula CO · R where Z is the acyl radical of a polybasic carbon with acid halides or ester acid halides or N-substituted or N-unsubstituted amide acid halides polybasic carboxylic acids and optionally then one in the Group - Z-Y primarily formed carboxylic acid ester group saponified. © 609 8K / 434 3.57