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New method for preparing iopromide

A technology of iopromide and a new method, applied in the field of preparation of iopromide, can solve the problems of reducing compound polarity, low yield, large protecting group and the like

Active Publication Date: 2015-11-04
白银京宇新药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0026] Route 6 reduces the polarity of the compound by protecting the methoxyacetyl group, and then removes the double-substituted by-products by crystallization. Although this method reduces the number of reaction steps, the starting materials are expensive, the protective group is relatively large, and it is difficult to Disadvantages such as deprotection
[0027] In summary, the current synthesis process has the disadvantages of difficult removal of double-substituted by-products, many reaction steps, low yield, and expensive and difficult-to-obtain raw materials. Cheap and easy to get, high yield, high purity process for preparing iopromide is of great significance

Method used

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  • New method for preparing iopromide

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Embodiment 1: Synthesis of 5-methoxyacetamido-2,4,6-triiodoisophthaloyl chloride (formula III):

[0036] Dissolve methoxyacetyl chloride (54.6g, 0.50mol) in 100mL of dry DMA, add dropwise 5-amino-2,4,6-triiodoisophthalic acid dichloride (Formula II) at a temperature controlled at 10°C (100.0 g, 0.17 mol) of DMA solution in 300 mL, after dropping, react at room temperature for 24 hours. After the reaction is completed, the reaction solution is poured into ice water, and a white solid is precipitated immediately, stirred for 15 min, filtered with suction, and the filter cake is dissolved in dichloromethane, and then washed with saturated NaHCO 3 solution and saturated NaCl solution were washed twice each, and the organic layer was added with anhydrous NaCl 2 SO 4 After drying and desolvation, 101.1 g of white solid was obtained with a yield of 90.2%.

Embodiment 2

[0037] Embodiment 2: Synthesis of 5-methoxyacetamido-2,4,6-triiodoisophthalic acid (2,3-dihydroxypropyl)amide chloride (formula IV):

[0038] Dissolve 5-methoxyacetamido-2,4,6-triiodoisophthaloyl chloride (formula III) (60.0 g, 0.09 mol) in 400 ml DMA, add triethylamine (9.07 g, 0.09 mol) , the temperature was lowered to below -10°C, and 200ml of DMA-dissolved 3-amino-1,2-propanediol (8.18g, 0.09mol) solution was slowly added dropwise, and the reaction was continued at -10°C for 10h. Suction filtration, the filtrate was evaporated under reduced pressure to remove most of DMA, then CH was added dropwise 2 Cl 2 solution, a white solid was precipitated, filtered by suction, and dried to obtain 42.2 g of a white solid, with a yield of 65%.

Embodiment 3

[0039] Example 3: 5-Methoxyacetamido-2,4,6-triiodoisophthalic acid [(2-oxo-1,3-dioxolan-4-yl)methyl]acyl

[0040] Synthesis of amine chloride (formula V):

[0041] 5-methoxyacetamido-2,4,6-triiodoisophthalic acid (2,3-dihydroxypropyl)amide chloride (formula IV) (40.0 g, 0.055 mol) was dissolved in 300 ml THF, After stirring and completely dissolving, solid phosgene (19.7 g, 0.066 mol) dissolved in 100 ml THF was added dropwise at room temperature. After the reaction was completed, evaporate to dryness under reduced pressure to obtain 39.4 g of off-white powder with a yield of 95%.

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Abstract

The invention relates to a preparation method of iopromide. 5-methoxylacetamido-2,4,6-triiodo m-phthalic acid[(2-oxo-1,3-dioxolame-4-yl)methyl]amido chloride (Formula V) and 5-methoxylacetamido-2,4,6-triiodo m-phthalic acid{[(2-oxo-1,3-dioxolame-4-yl)methyl]-(2,3-dyhydroxyl-N-methyl propyl)}diamide (Formula VI) are introduced to be used as intermediates. Even if there is no additional purification step, a bismer by-product generated during the reaction also can be removed by introduction of the intermediates and high-purity iopromide can be prepared at high yield.

Description

technical field [0001] The present invention relates to the preparation method of iopromide, more specifically relate to using 5-methoxyacetamido-2,4,6-triiodoisophthalic acid [(2-oxo-1,3-dioxolane Cyclo-4-yl)methyl]amide chloride (formula V) and 5-methoxyacetamido-2,4,6-triiodoisophthalic acid {[(2-oxo-1,3-di Oxolane-4-yl)methyl]-(2,3-dihydroxy-N-methylpropyl)}diamide (formula VI) as the preparation method of iopromide intermediate. [0002] [0003] According to the present invention, by purifying the intermediate of formula VI, the bismer by-products that lead to the reduction of the purity of iopromide produced during the preparation of iopromide can be easily removed without additional purification steps to remove the bismer by-products Product, finally can obtain high-purity iopromide in high yield. Background technique [0004] Iopromide (Formula I) is widely used clinically as an X-ray contrast agent. The preparation methods reported in the current literature a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C237/46C07C231/12
Inventor 黄强袁野徐卉姝孙银玲
Owner 白银京宇新药业有限公司
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