A kind of synthetic method of the key intermediate of contrast agent iodixanol impurity e
A technology for iodixanol and a synthesis method, which is applied in chemical instruments and methods, preparation of organic compounds, organic chemistry, etc., can solve the problems of difficult removal, small differences in physical and chemical properties and polarities of substances, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0022] Preparation of 5-amino-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide
[0023] Add 70g of 5-amino-N,N-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide into a 500ml reaction flask, add 420g of Ionized water, add 5g of 98% concentrated sulfuric acid, 17g of iodine, 22g of iodic acid, heat up to 90°C, keep stirring and react for 25h, sample the reaction solution, detect by HPLC, wherein the target product content is about 40%, cool down to 60°C , add 10% hydrazine hydrate dropwise, adjust the reaction solution until the KI-starch test paper does not develop color, use liquid caustic soda to adjust the pH to 7.5, cool down to 10°C for crystallization and stir for 24 hours, filter with suction to obtain a yellow-brown solid, 60°C under normal pressure Drying to obtain 18g of solid, HPLC detection, the content of the target product is 70%, the yield is 30%.
Embodiment 2
[0025] Separation and purification of 5-amino-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide
[0026] Put 18g of the product of Example 1 into a 500ml reaction bottle, add 200ml of deionized water, heat up to 60°C to dissolve, cool down to room temperature, add to LX-18 resin column, use deionized water to elute, and elute to the target After the product starts to flow out, use 30v / v% methanol aqueous solution to elute, and stop the elution when the content of the target product in the effluent is lower than 80%, evaporate the eluate containing the target product to dryness under reduced pressure, and slip out After methanol, a white solid was obtained, which was dissolved by adding 100 g of deionized water to raise the temperature, cooled to 7° C. for crystallization for 20 h, and suction filtered to obtain a white solid. After drying, 12 g of the target product with an HPLC content of 98% was obtained, with a yield of 19%.
Embodiment 3
[0028] Preparation of 5-amino-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide
[0029] Add 70g of 5-amino-N,N-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide into a 500ml reaction flask, add 300g of Deionized water, add 9g of 98% concentrated sulfuric acid, 15g of iodine, 19g of iodic acid, heat up to 85 ° C, keep stirring and react for 24 hours, sample the reaction solution, detect by HPLC, wherein the target product content is about 74%, cool to 60 ℃, add 10% hydrazine hydrate to adjust the reaction solution until the KI-starch test paper does not develop color, use liquid caustic soda to adjust the pH to 7.5, cool down to 10 ℃, crystallize and stir for 24 hours, filter with suction to obtain a golden yellow solid, 65 ℃ normal pressure After drying, 40 g of solids were obtained. The content of the target product was 83% and the yield was 66% according to HPLC detection.
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More