SU514566A3 - The method of obtaining derivatives of triiodinated aminobenzenecarboxylic acids, or their low alkyl esters, or salts - Google Patents

Description

Re is alkylene with a straight or branched carbon chain containing a maximum of 5 carbon atoms in the case when R2 is lower alkyl or alkenyl, or A is carboxyl per group, or H3 is an alkylenecarboxylic acid residue, or their salts, or lower alkyl esters are obtained by reacting triiodinated aminobenzenecarboxylic acids of general formula II where Y is a halogen atom, Kg A group is hydrogen, a carboxyl group, is carboxyl group esterified with aliphatic alcohols, an acid chloride residue or a group in which Rs is lower kil or alkenyl, or Re-COOH or Re-COOR radicals, where R is alkyl and RI and Re have the indicated meaning, or Re together with Ri and N forms a morpholino-piperidino or pyrrolidine radical, with a compound of general formula III where R4 and Rs have the indicated meaning and one of the radicals X and X in the compounds of formula II and III is hydrogen, the other is -CORg, and Ne is hydrogen, alkyl, maximum containing 4 carbon atoms, alkylenecarboxylic acid residue, containing maximum 4 carbon atoms, or residue alkylenecarboxylic acid lower alkyl ester in which the acidic the residue has a maximum of 4 carbon atoms and in the case when Rg is lower alkyl .. or alkenyl, or A is a carboxyl group or its allylic ester residue, or Rg is a residue of an alkylene carboxylic acid lower alkyl ester or an alkylene carboxylic acid residue, and is formed compound interacting with pivalent phosphorus halide, taken in equimolar amount, in an inert organic solvent medium, followed by reacting the obtained compounds or their hydrochlorides with amines of general formula IV and isolation of the desired product in free form, as an ester or salt. Example 1. 133.3 g of 3-amino-2,4,6-triiodobenzoyl chloride are dissolved in toluene, 37.5 ml of dimethylformamide and 31.3 ml of POCl3 are added and the solution is refluxed for 1 hour. The resulting hydrochloride, 3d-methylaminomethyleneimino-2,4,6-triiodobenzoyl chloride, after cooling, is sucked off and washed with ether. This product is then coated with ether, water is added and 250 ml of 4 N are added dropwise with ice-cooling and good stirring. NaOH. After separation of the ether layer, the latter is washed with ice water, dried on NaCl and evaporated. The oily evaporation residue is dissolved in hot cyclohexane, treated with activated charcoal and the solution is clarified by filtration. During slow cooling, 123.37 g of yellow 3-dimethylaminomethyleneamino-2, 4,6 - triyodobenzoyl chloride crystallize from it, with a pouring point of 100-il05 ° C. 58.8 g of the resulting acid chloride is dissolved in chloroform and a solution of 30.0 g of methyl N-allyl-p-aminopropionic acid ester in chloroform is added. The reaction mixture begins to boil, to complete the reaction, it is boiled for another 2 hours with a reverse flow, then the solution is washed with water, 5% tartaric acid and K2CO3 solution, dried on CaCla and evaporated. The residue is dissolved in hot form in methanol, 30.0 g of M- (3-dimethylaminomethylamino-2,4,6 -triodo-benzoyl) -N-allyl-p-aminopropionic acid methyl ester crystallizes with mp. 86-98 ° C, with a condensation of the stock solution to 1/3 - the remaining 22.0 g with m. Pl. 85-100 ° C. 25 g of the ester was saponified in an excess of an aqueous solution of NaOH at 80 ° C, the resulting solution was clarified by filtration and the pH was adjusted to 6 in a cold state by adding HCl. The amorphous precipitate was sucked off and dried in a desiccator. The yield is 22.0 g of amorphous M- (3-dimethylaminomethylaminomethylene-amino-2,4,6-triyodbenzoyl) -Y-allyl-p-aminopropionic acid, m.p. 94-106 ° C. Calculated,%: C, 28.21; H 2.66; N 6.17; J 55.89. Found,%; C 28.0; H 2.8; N 6.3; J 54.5. Example 2. 2.76 g of methyl complex of N- (3-amino-2,4,6-triyodbenzoyl) -N-feil-p-aminopropionic acid are dissolved in absolute toluene and after addition of 1.5 ml of methyl formamide and 1.25 ml of POCR are boiled for 1 hour. The oil that precipitates is separated.

after cooling, it is dissolved in methanol and precipitated with ether again. When rubbed with ether, crystallization will occur. The output of 6.2 g of brownish hydrochloride of methyl ester N- (3-dimethylaminomethylamino2, 4,6-triyodobenzoyl) -Y-phenyl - p - aminopropionic acid, so pl. 130-135 ° C. Treatment with an excess of NaHCOa get ether base with so pl. 70-77 ° C, which is washed in the same manner as in Example 1 with an aqueous alkaline solution. The melting point of the amorphous N - (3-dimethylaminomethylene-amino-2,4,6-triiodo-benzoyl) -Y-phenyl-p-aminopropionic acid is 92-116 ° C.

Calculated,%: C 31.82; H 2.58; N 5.86; J 53.09.

Found,%: C 31.1; H 2.7; N 5.8; J 53.5.

Example 3. 18.0 g of the acid chloride prepared according to Example 1 was dissolved in chloroform and 9.5 g of e-aminocaproic acid methyl ester dissolved in chloroform was added. The reaction mixture is heated to boiling. Boil another 90 minutes and then wash the chloroform solution with water, an aqueous solution of tartaric acid and K2CO3 solution, dry on CaClI and evaporate. The evaporation residue is dissolved in hot form in methanol and clarified by filtration. From the solution, 14.0 g of M- (3-dimethylaminomethyleneamino-2, 4,6-triyodbenzoyl) -e-aminocaproic acid, crystalline methyl ester, m.p. 139-142 ° C, with the condensation of the mother liquor the remaining 6.2 g of the same product crystallize, t. Pl. 128-140 ° C. For saponification, 18.0 g of this ester is suspended in 2 g of NaOH and boiled until dissolved. After filtration with dilute HC1, the pH is adjusted to 5, and oily acid is obtained, and, upon cooling with ice water, it solidifies. After suction and drying in a desiccator, 12.0 g of amorphous N- (3-dimethylaminomethylamino-2,4,6-triyodbenzoyl) -8-aminocaproic acid are obtained, m.p. 90-100 ° C.

Calculated,% C 28.13; H 2.95; N 6.15; J 55.74.

Found,%: C 28.1; H 3.0; N 6.2; J 44.4.

Example 4. 22.8 g of 3-amino-5-Y-methylcarbamyl-2, 4,6-triiodobenzoic acid are suspended in dioxane, displaced with 25 ml of dimethylformamide and 25 ml of POCl3 are boiled for 90 minutes. Then the reaction mixture is evaporated to dryness in vacuo and the residue is carefully mixed with 200 ml of water. The resulting crystallization is filtered off with suction, dissolved in water with NaOH, clarified by filtration, and again precipitated with dilute HCl. Get 23.5 g of hydrochloride of 3-dimethylaminomethylamino-5H-methylcarbamyl-2, 4,6-triyodobenzoic acid, with so pl. from 300 ° C with decomposition.

Calculated,%: C, 21.73; H 1.98; N 6.33; J 57.38.

Found,%: C 21.3; H 2.0; N 6.1; J 57.1.

Example 5. 53.1 g of 3-amino-5-K-meth11lcarbamyl-2, 4,6-triiodobenzonyl chloride are suspended in chloroform, 52.2 g of dimstil acetamide and 121.8 g of POCl are added and the solution is boiled for 4.5 hours After cooling, the product obtained is filtered off with suction, suspended in chloroform, and dissolved by the addition of triethylamine. The solution is sucked off and in vacuum. Obtain 16.8 g of amorphous (G-dimethyllaminoethylene-amino) -2,4,6-triyodobenzoyl - N - (umethoxypropyl) -p-aminopronionic acid, so pl. 90-110 ° C.

Calculated,%: C, 29.73; H 3.33; N 5.78; J 52.30.

Found,%: C 29.0; H 3.2; N 5.6; J 52.7.

Claims (1)

Invention Formula 90 Method for preparing derivatives of triiodinated aminobenzenecarbopic acids of general formula 1 R-, a- 1-. CON TO/ .R, RrC-N: R 5 where A is hydrogen, carboxyl group or group .. Rn -CON ; in which RI is hydrogen, alkyl or alkenyl containing at most 4 carbon atoms, alkoxyalkyl containing at most 6 carbon atoms, benzyl or phenyl radical; R2 is lower alkyl, alkenyl, the radical -Kb-COOH or the radicals Ri and R2 together with the nitrogen atom represent a morpholino, piperidine or pyrrolidine radical; Ra is hydrogen, alkyl containing at most 4 carbon atoms, or an alkylenecarboxylic acid residue containing at most 4 carbon atoms; R4 is hydrogen or lower alkyl; Rs is alkyl or alkenyl containing at most 4 carbon atoms, alkoxyalkyl containing at most 6 carbon atoms, beisyl or phenyl, or R4 and Rs together with the nitrogen atom represent a pyrrolidino, piperidine or morpholine residue; Re is alkylene with a straight or branched carbon chain containing at most 5 carbon atoms in the case when R2 is lower alkyl or alkenyl, or A is a carboxyl group, or RS is an alkylenecarboxylic acid residue, or their lower alkyl esters, or salts, characterized in that the trihydrodimentioned amimobenzenecarbopic acid triiodo compounds of the general formula II Sow Hn-x halogen atom, group RI - “U / N A is hydrogen, a carboxyl group, is esterified with aliphatic alcohols, a carboxyl group, an acid chlorohydride residue or a group / Nl -to; AT/ in which Rs is lower alkyl or alkenyl, pl or Re-COOH or Re-COOR radicals, where R is alkyl and RI and Re have the indicated meaning, or Rg together ciRi and N forms a morpholPO, piperidino or pyrrolidine radical, subjected to interaction with the compound of General formula III , R. X-N; s where R4 and RS have the indicated value and one of the radicals X and X in the compounds of the formula II or III is hydrogen, the other is -CORg, and Rg is hydrogen, alkyl, maximum containing 4 carbon atoms, residue of alkylenecarboxylic acid, containing maximum 4 atoms carbon, or a residue of an alkylenecarboic acid lower alkyl ester, in which the acid residue has at most 4 carbon atoms in the case when Rg is lower alkyl or alkenyl, or A is a carboxyl group or its allyl ester residue, or Rg is a lower alkyl residue with ozhnogo alkilenkarbonovoy acid or ester residue alkilenkarbonovoy acid and reacting the resulting compound with a nivalent phosphorus halide, taken minimum in an equimolar amount, in an inert organic solvent followed by reacting the resulting compounds or their hydrochlorides with amines of general formula IV / "- g, -.s and the selection of the target product in free form, in the form of ester or salt in a known manner.