• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    This invention relates to compounds of the formula: <IMAGE> (I) in which:
    公开号:SU793387A3
    申请号:SU772469149
    申请日:1977-04-08
    公开日:1980-12-30
    发明作者:Тийи Ги；Жан-Шарль Ардуэн Мишель；Лотру Жан
    申请人:Гербе С.А. (Фирма)；
    IPC主号:
    专利说明:

    an amine of the general formula I I I COOH
    L
    n-yo (ynO „1 H2, (w) Kz
    where n, Rj t R% are indicated, followed by acylation of the free amino group of the obtained amide with an acid chloride to carry out the process in any sequence in a polar solvent at IS-IOO C in the presence of a hydrogen chloride acceptor, for example, triethylamine.
    Example 1. Preparation of 2,4,6-triyod-5-acetamide-1, 3-bis-f {2, 4, 6-triyod-3-ethylcarbamoyl-5-carboxyphenyl) -carbamoyl-benzene.
    Preparation of 2,4,6-triiodo-5-acetamidoisophthalic acid dichloride.
    To 2,4,6-triiodo-5-aminoisophthalic acid dichloride (150 g, 0.252 mol) in 300 ml of DMAS. (Dimethylacetamide), 80 ml of acetyl chloride are added and kept overnight in an ice bath. The resulting reaction mixture was poured into 1.5 liters of water. The precipitate is filtered off and washed twice with water. After drying at 45 ° C, 159 g of product (99%) are obtained. The purity is controlled by chromatographyl on a thin layer on a silica gel plate. Elute: benzene / ethyl ethyl ketone / formic acid - 60/25/20.
    Non-acetylated product Rf0.90
    Acetylated product Rf0,85
    Iodine content,% 99 Chlorine content,% 99 A mixture of 2,4, b-triyod-N-hydroxyethyl-3-carbamoyl-5-amino-acetamido benzoic acid (328 g, 0.498 mol) is poured into the resulting dichlorohydride (158 g, 0249 mol) DMAS (650 ml) and triethylamine (140 ml) and shaken overnight at 50 ° C. To precipitate the precipitate, treat with pure HC, filter, wash with water, redissolve the product in NaOH (2N adjust pH to 6-7 using acetic acid and treated with charcoal for one night at 60 ° C. The coal is filtered off and the precipitate of the desired product is precipitated with a clean one, filter comfort, promyvgiot twice with water and dried.
    104 g of product are obtained (yield: 22%).
    Purification with sodium salt. To the resulting 55 g of product, 165 ml of water and NaOH (17 N) are added to bring the pH to 7-8.
    The solution is heated to 85 ° C, then 275 g of NaOH (17 N) is added and, after cooling to room temperature, is left to stand overnight to crystallize in a refrigerator, crystallization is carried out by scrape walls. The crystals are filtered, clarified with NaOH (10N)
    The product is dissolved in - 150 ml of water, then precipitated with pure HC. After filtration and washing with water, it is dried. Get 20 g of creamy product.
    The purity is controlled by thin layer chromatography on a silica gel plate. Elute: ethyl acetate / isopropanol / ammonia 25/35/40.
    Source amine Rf 0.40 Dichlorohydrin Rf 1.00 Product Rf0.30
    Iodine content,% 101 Methylate content,% 100 Example 2. Preparation of 2,4,6-triiodo-5-acetamide-1,3-bis-f (2,4,6-triiodo-3-methylcarbamoyl-5carboxyfeNIL) -carbamoylmethylcarbamoyl -benzene.
    It is obtained by condensation of the acid chloride obtained in Example 1 with 2.4, b-triyod-3-methylcarbamoyl-B-acetamido benzoic acid in DMAC as in Example 1.
    The purity is controlled by thin layer chromatography on a sipagel plate.
    Elute: ethyl acetate / isopropanol / ammonia - 25/35/40
    Source amine Rf 0.6 Product Rf0.513
    Rutanol / water / acetic acid 50/25/13
    Source Amine Rf 0.2 Product Rf0.15
    Iodine content,% 100.2 Methylate content,% 99 Example 3. Preparation of 2,4,6-triiodo-5-acetamide-1,3-bis (2,4,6-triiodo-5-carboxyphenyl) -carbamoylmethylcarbamoyl benzene .
    The condensation of the acid chloride obtained in Example 1 with 2,4,6-triiodo-3-amino-acetamido-benzoic acid was blown into DMAC according to the method described in Example 1.
    The purity is controlled by chromatography in a thin layer on a silica gel plate.
    Elute: butanol / water / acetic acid - 5/25/13.
    Source Amine Rf 0.37 Product R f0.43
    Benzene / methyl ethyl ketone / formic acid 60/25/10
    Source Amine Rf 0.00 Product Rf0.15
    Content of iodine,% 101 Content of ethyl acetate,% 100.2
    权利要求:
    Claims (1)
    [1]
    Example 4. Preparation of 2,4,6-triyod-5-acetamide-1,3-bis- (2, 4, 6-triyod-3-acetamide-5-carG.1lxyphenyl) -carbamoylmethylcarbamoyl-eol. The condensation of the acid chloride obtained in Example 1 with 2,4, b-triiodo-3-acetamide-5-amino-acetamido-benzoic acid is carried out in DMAC according to the method described in Example 1. The purity is monitored by chromatography on a thin layer on s kagel plate. Elute: butanol / water / acetic acid - 50/25/13. Source amine Rf 0.20 Product Rf0.15 Iodine content,% 99.2 Methylate content,% 99 Example 5. Preparation of 2,4,6-triiodo-5-acetamide-1,3-bis- (2.4, b -triiod-M-methyl-3-acetamide-5-carboxyphenyl) -carbamoylmethylcarbamoyl-benzene. The condensation of the acid chloride obtained in Example 1 with 2.4, b-triyo-M-methyl-3-acetamide-5-amino-acetates with benzoic acid is carried out in DMAS according to the method described in Example 1. The purity is monitored by means of chromatography on a thin a layer on the C kagel plate. Elute: butanol / water / acetic acid - 50/25/13. Source amine Rf 0.20 Product Rf0.25 Iodine content,% 98.6 Methylate content,% 99.3 Example 6. Preparation 2.4, b-triiod-5-acetamide-1,3-bis- (2.4 , b-triiodo-M-hydroxyethyl-3-carba yl-5-carboxyphenyl) -N-methylcarbamo methylcarbamoyl-benzene. The condensation of the obtained acid chloride with 2,4, b-triiodo-N-oxy-3-carbamoyl-N-methyl-5-amino-acetamido benzoic acid in DMAS is conducted according to the method described in Example 1. The purity is controlled by chromatography on a thin layer on a silica gel plate. Elute: butanol / water / acetic acid - 50/25/13. Source amine Rf 0.23 Product R f0.17 Example 7. Preparation of 2,4,6-triiodo-5-acetamido-1,3-bis- (2,4, -triiod-5-carboxyphenyl) -carbamoyl ethylcarbamoyl - benzola. The acid chloride obtained in Example 1, with 2,4,6-triiodo-3-aminopropionamidobenzoic acid, is condensed with DMAS under the conditions described in Example 1. The reaction was monitored by thin-layer chromatography on silica gel plates. PLN: benzene / methy; ethyl KTofi / muroVyna acid - 60/25/20 Initial amine Rf 0.10 Reaction product Rf 0.30 Ethyl acetate / isopropanol / ammonia - 25/35/40. Source amine Rf 0,63 Reaction product Rf 0,85 Example 8. Preparation of 2,4,6-triiod-5-acetamide-1, 3-bis- (2,4,6-triiod-M-methyl-3-carboxyphenyl ) -carbamoylpropylcarbamoyl-benzene. Condensation of the acid chloride obtained in Example 1 with 2,4,6-triiodo-M-methyl-3-carbamoyl-5-aminobutane amidobenzoic acid is carried out in D1-1AC under the conditions described in Example 1. The reaction is monitored with a thin layer. chromatography on silica gel plates. Elyueite: benzene / methyl ethyl ketone / formic acid - 60/25/20. Original amine Rf 0.00 Reaction product Rf 0.10 Ethyl acetate / isopropanol / ammonia - 25/35/40 Original amine Rf 0.50 Reaction product Rf 0.80 Example 9. Preparation of 2,4,6-triiod-5-acetamide -1, 3- (2,4, 6-triyod-M-methyl-3-carbamoyl-5-carbo-1 syphenyl) -carbamoyl-tylocarbamo; b. -benzene. The acid chloride obtained in Example 1 with condensation of 2,4,6-triiodo-M-methyl-3-carOa; -: P1; l-5-amine.-1hexanamido benzoic acid is carried out in DMAS under the conditions described here; in Example 1. The reaction was monitored by thin layer chromatography on silica gel plates. Eluent: benzene / methyl ethyl ketone / Niyravirina acid - 60/25/20. Initial amine Rf 0.00 Reaction product Rf 0.16 Ethyl acetate / from NOL / ammonia oprop - 25/35/40 Original amine Rf 0.55 Reaction product Rf 0.85 Example 10. Preparation 2,4,6- triiodo-5-acetamide-1, 3-bis- (2,4,6-triiodo-Y-hydroxyethyl-3-carbamoyl-5-carboxyphenyl) -carbamoyl propylcarbamoyl benzene. Condensation of the acid chloride obtained in Example 1 with 2,4, b-triiodo-M-hydroxyethyl-3-carbamoyl-5-aminobutanamylbenzoic acid is carried out in DMAS under the conditions described in Example 1. The reaction is monitored by thin layer chromatography on plates with silica gel. Eluent: ethyl acetate / isopropanol / ammonia - 25/35/30. Is;: single amine Rf 0.45 Reaction product Rf 0.80 Claims of the invention. Method of obtaining substituted common atoms of the formula I. .. NCOCCHjI HNOC Jjx coNHr.HjJf CON where R represents a hydrogen atom, a group of the formula -C-NH -R. II 4 8 which Cd is C -C4-alkyl or, .. -C.-oxyalkyl, a group of the formula -N-C-R ,. I II b. in which R is C-C-alkyl and R is a hydrogen atom or C, -C-alkyl, R c represents a hydrogen atom or C-alkyl, n is an integer from 1 to 5 or their salts, characterized in that the acid dichloride acids of general formula II are reacted with an amine of general formula N-COCCHjI NHj, R-Jy where n, Rg and R are as indicated above, followed by acylation of the free amino group of the obtained amide with an acid chloride to carry out the process in any sequence in a polar solvent at 15- 100 ° C in the presence of an acceptor of hydrogen chloride. Sources of information taken into account in the examination 1. N. Vorozhtsov. Basics of synthesis of intermediate products and dyes. Goskhimizdat, 1950, p. 592.
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    引用文献:
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    BE787669A|1971-08-17|1973-02-19|Schering Ag|N-METHYL-DICARBOXYLIC ACID TRIIODS ANILIDES AND THEIR PREPARATION PROCESS|
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    AR207465A1|1974-05-31|1976-10-08|Guerbet Lab Andre|PROCEDURE FOR THE PREPARATION OF TRIIODO-2,4,6- -AMINO-ALKANOYLAMINOBENZOIC ACID DERIVATIVES FROM TRIIODO-2,4,6- -AMINOALKANOYLAMINOBENZOYL) -AMINO-ALKANOYL-AMINOBENZOIC AND OF TRIIODE-2,4,6-BIS -CARBAMOYL-METHYL) -AMINOALKANOYL-AMINOBENZOIC ACID|FR2427326B2|1978-05-31|1983-08-12|Guerbet Sa|
    DE2909439A1|1979-03-08|1980-09-18|Schering Ag|NEW NON-ionic x-ray contrast agents|
    DE3001293A1|1980-01-11|1981-07-16|Schering Ag Berlin Und Bergkamen, 1000 Berlin|IONIC 5-C SUBSTITUTED 2,4,6-TRIJOD ISOPHTAL ACID DERIVETE|
    FR2511870B1|1981-08-28|1984-06-22|Guerbet Sa|
    JPH04350468A|1991-04-23|1992-12-04|Asahi Breweries Ltd|Liquid cooler|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB14343/76A|GB1539791A|1976-04-08|1976-04-08|X-ray contrast media|
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