- New Methods for Preparing an Intermediate of Contrast Medium and Methods for Preparing Contrast Medium
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A manufacturing method of the present invention reduces treatment processes when manufacturing a contrast medium or an intermediate thereof, and thus generates less waste solvent, thereby being eco-friendly and capable of significantly reducing a manufacturing cost. Therefore, the manufacturing method of the present invention is economical and suitable for mass production since the production cost of the contrast medium can be greatly reduced.
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Paragraph 0137-0140
(2020/10/07)
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- New Methods for Preparing an Intermediate of Contrast Medium and Methods for Preparing Contrast Medium
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The present invention relates to a method for preparing an intermediate of contrast agent or contrast agent. Also, the manufacturing cost can be significantly reduced. , The manufacturing method of the present invention can greatly reduce the production cost of contrast agents and is suitable for mass production. (by machine translation)
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Paragraph 0137-0140
(2020/10/14)
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- Preparation method of ioversol
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The present invention provides a novel preparation method of ioversol. The method comprises the following steps: adding a protection group to 5-hydroxyacetylamino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide, conducting an alkylation reaction under an alkaline condition, and carrying out deprotection, so as to prepare ioversol. According to the preparation method disclosedby the invention, hydroxyl is protected before alkylation, so that the generation of ioversol rearrangement impurities (impurity II) in the alkylation preparation process is effectively controlled, the refining difficulty of a finished product is reduced, the refining yield is increased, and the preparation method is more suitable for industrialization.
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- METHOD FOR PREPARING TRIIODOISOPHTHALAMIDE X-RAY CONTRAST MEDIA IOVERSOL
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The present invention relates to a method for producing an X-ray contrast agent ioversol. More specifically, the present invention relates to the method for manufacturing the X-ray contrast agent ioversol in which an inorganic base, chloride and the like are added to 5-(2-hydroxyacetamido)-N,Nandprime;-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide(chemical formula 9), followed by performing an N-alkylation reaction, thereby being able to easily separating and removing inorganic salts generated during reaction without ion exchange resin treatment while shortening an existing manufacturing time, and thus being able to minimize reaction impurities.COPYRIGHT KIPO 2020
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Paragraph 0046-0070
(2020/03/05)
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- Synthetic method of ioversol
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The invention discloses a synthetic method of ioversol. The synthetic method comprises the following steps: firstly, dissolving an ioversol intermediate 5-chloroacetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide into a mixed solution of methanol, ethanol and barium hydroxide, and then adding 2-chloroethanol to carry out a nitrogen alkylation reaction to obtain a targetproduct ioversol; carrying out reduced pressure distillation on the obtained mixed solution to separate out the methanol, and separating out barium chloride by precipitation filtration according to the fact that the barium chloride generated after the nitrogen alkylation reaction is soluble in methanol and is insoluble in ethanol; and finally recrystallizing the solution containing the target product ioversol by using propylene glycol monomethyl ether to obtain the target product ioversol. According to the synthetic method disclosed by the invention, the quality and the yield of the synthesisof the ioversol are effectively improved, and the synthesis process is simplified.
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Paragraph 0013; 0014; 0015; 0016; 0017; 0019; 0020; 0021
(2019/02/13)
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- Method for preparing ioversol
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The invention discloses a method for preparing ioversol. Compound I: [5-hydroxyacetamido]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodide-1,3-phthalamide, chloroethanol or analogues thereof is used as raw materials, disodium hydrogen phosphate or dipotassium hydrogen phosphate is used as acid binding agent, and the reaction is carried out in a solvent, and after the reaction is completed, ioversol is obtained through post-treatment. As that buff base disodium hydrogen phosphate or disodium potassium hydrogen phosphate is used as the acid binding agent, the reaction condition is relatively mild,and the disadvantage of unstable pH in the reaction process is overcome; therefore, the ioversol impurity prepared by the invention is small and less, in particular, the alkoxy impurity can be controlled below 0.5%, and the yield is high, and the yield can reach 90-98%, and the method has features of green environmental protection and simple operation.
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Paragraph 0028-0048
(2019/09/13)
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- preparation method of contrast agent
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The present invention relates to a method for producing a contrast medium with high purity and high efficiency, and since no methyl iodide and the like are used in a production process, no salt is generated or only a very small amount thereof is generated, and a high purity and high efficiency contrast medium can be produced without complicated purification and washing steps. In addition, a small amount of salt can be easily removed by washing with water.COPYRIGHT KIPO 2018
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Paragraph 0116; 0120; 0121; 0122-0125
(2018/10/16)
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- Preparation method of ioversol
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The invention provides a preparation method of ioversol. Particularly, the method provided by the invention comprises the following steps: carrying out alkylation reaction on 5-chloracetylamino-N,N'-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-phenyldiformamide and chloroethanol by using sodium hydroxide/sodium borate or sodium hydroxide/lithium chloride; and meanwhile, directly hydrolyzing the product by a one-pot multistep process, and carrying out desalting and purification to prepare the ioversol. The method simplifies the production technique process, effectively controls the generation of irremovable impurities, and is suitable for industrial production.
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Paragraph 0040; 0041; 0042; 0043; 0044-0062
(2017/05/10)
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- Preparation method for ioversol
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The invention provides a preparation method for ioversol. Specifically speaking, the method comprises the following steps: (1) performing an alkylation reaction on 5-chloracetyl amino-N,N'-bi-(2,3- dyhydroxyl propyl)-2,4,6-triiodo-1,3-phthalic diamide and chlorethyl alcohol under an alkaline condition; (2) hydrolyzing through sodium acetate to obtain the ioversol. A container of which the inner wall is coated with a corrosion-resistant coating is used in the reactions of the former two steps, and the water with the iron content of below 0.05 ppm is used. The method can effectively avoid the production of impurities which are difficult to remove, and is suitable for industrial production.
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Paragraph 0040; 0042; 0043; 0045; 0050; 0052; 0068
(2017/07/19)
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- PROCESSES FOR THE PREPARATION OF PURE IOVERSOL
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The invention relates to processes for the preparation of pure ioversol. The invention also relates to processes for the preparation of N,N'-bis(2,3-dihydroxypropyl)-5-(2- chloroacetamido)-2,4,6-triiodoisophthalamide and N,N'-bis(2,3-dihydroxypropyl)-5- [N-(2-hydroxyethyl)-2-chloroacetamido] -2,4,6-triiodoiso phthalamide, useful intermediates for the preparation of ioversol.
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Page/Page column 15; 11-12
(2008/12/07)
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- A selective process for n-alkylation in competition with o-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes
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This paper describes a selective process for the N-alkylation of substrates that contain 1,2-diol groups. The developed approach utilises temporary protection of the diol groups by boric acid, Borax, or metaborate. The introduction of the boron-containing groups into the substrate may provide, in addition to affording the intended protection of the hydroxyl groups that may otherwise act as nucleophilic sites, the advantages of improved solubility of the substrate in water that is used as solvent. Moreover the N-alkylation and the deprotection of the diols are performed in one pot, and the formation of undesired O-alkylated by-products is significantly reduced. The paper gives examples from the synthesis of several X-ray contrast agents used in medical imaging diagnostics: iohexol (Ominipaque, Nycomed Imaging); iopentol (Imagopaque, Nycomed Imaging); iodixanol (Visipaque, Nycomed Imaging); ioversol (Optiray, Mallinckrodt).
- Bjorsvik, Hans-Rene,Priebe, Hanno,Cervenka, Jan,Aabye, Arne W.,Gulbrandsen, Trygve,Bryde, Arnt Christian
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p. 472 - 478
(2013/09/07)
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- Smiles rearrangement as a tool for the preparation of 5-[(2-hydroxyacyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamides: Main pathway and side reactions
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In the preparation of 5-[(2-hydroxyacyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamides 1a-h from 2a-h two conditions using stoichiometric amounts of base (method A - aq NaOH at 50°C; method B - MeONa in DMF at r, t.) were used. Yields are good to excellent provided that the right conditions are chosen. Primary amides 2a,b give 1a,b with method B only, whereas with method A extensive hydrolysis of the CONH2 moiety is observed. N-Methyl derivatives 2c,d afford 1c,d with either method. However, with method B long reaction times lead to the formation of large amounts of benzoxazinones, 4c,d. Under the same conditions, the pattern of side products which are formed from N-(hydroxyalkyl)phenoxyacetamides 2e-g is further complicated by: i) intramolecular cyclizations leading to bicyclic (7f,g) and tricyclic structures (5) ii) N-deacylation; iii) double Smiles rearrangement reactions.
- Anelli, Pier Lucio,Brocchetta, Marino,Calabi, Luisella,Secchi, Carlo,Uggeri, Fulvio,Verona, Sandra
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p. 11919 - 11928
(2007/10/03)
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