Preparation method of Iopromide

A technology of iopromide and triiodobenzoic acid, which is applied in the field of preparation of iopromide, can solve the problems of increasing iopromide synthesis steps and excessive amount

Active Publication Date: 2012-02-15
ZHEJIANG STARRY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But, in above-mentioned reaction scheme, if the amount of 2,3-dihydroxypropylamine used is too much, can produce the by product of formula (5) equally
Simultaneously, reaction scheme 3 is compared with reaction scheme 1, although the method for removing formula (5) by-product has been improved, but increase formula (6) compound as intermediate, increase the synthetic steps of synthetic iopromide

Method used

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  • Preparation method of Iopromide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: Synthesis of 3-methoxyacetylamino-5-(2,3-diacetoxy n-propylcarbamoyl)-2,4,6-triiodobenzoic acid (Formula 8)

[0049] In the 2L there-necked flask equipped with a condenser tube, add the compound formula (7) 3-amino-5-(2,3-diacetoxy n-propylcarbamoyl)-2,4,6-triiodobenzoic acid ( 320g, 0.45mol), methoxyacetyl chloride (147g, 1.35mol), DMF (8ml), chloroform (1500ml), reflux reaction for 15 hours, and TLC detected that the reaction was complete. Concentrate under reduced pressure, add ethyl acetate (1500ml), stir at room temperature for 0.5 hours, suction filter, and dry to obtain formula (8) as a white solid compound (345g), with a molar yield of 97.3%.

Embodiment 2

[0050] Embodiment 2: the synthesis of 3-methoxyacetylamino-5-(2,3-dihydroxy n-propylcarbamoyl)-2,4,6-triiodobenzoic acid (formula 9)

[0051] In the 500ml there-necked flask, add compound formula (8) 3-methoxyacetamido-5-(2,3-diacetoxy n-propylcarbamoyl)-2,4,6-triiodobenzoic acid (87g , 0.11mol), sodium bicarbonate (65g, 0.77mol), water (261ml), 55 ℃ insulation reaction for 18 hours, TLC detection reaction is complete. Use 5% hydrochloric acid to adjust pH=5-6, filter with suction, concentrate the filtrate to dryness under reduced pressure, add absolute ethanol (100ml), filter, adjust the filtrate to pH=1-2 with 11% hydrochloric acid, concentrate to dryness under reduced pressure to obtain Formula (9) white solid compound (76.4g), the molar yield is 98.7%.

Embodiment 3

[0052] Embodiment 3: the synthesis of 3-methoxyacetylamino-5-(2,3-dihydroxy n-propylcarbamoyl)-2,4,6-triiodobenzoyl chloride (formula 4)

[0053] In the 1L three-neck flask equipped with a dry condenser, add the compound formula (9) 3-methoxyacetamido-5-(2,3-dihydroxy-n-propylcarbamoyl)-2,4,6-triiodo Benzoic acid (72.5g, 0.10mol) and thionyl chloride (720ml) were incubated at 65°C for 5 hours, and the reaction was completed by TLC. Concentrate under reduced pressure to remove thionyl chloride, add chloroform (150ml), stir at room temperature for 1 hour, filter with suction, and dry in vacuo to obtain formula (4) as a white solid compound (67.9g), with a molar yield of 94%.

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Abstract

The invention relates to a preparation method of Iopromide. 3-methoxy acetamino-5-(2,3-dihydroxy n-propylamine formyl)-2,4,6-triiodide benzoic acid shown as a formula (9) is used as an intermediate to provide a cheaper and more reasonable method for synthesizing Iopromide with high yield and purity.

Description

Technical field: [0001] The present invention relates to the preparation method of iopromide, more specifically relate to the 3-methoxyacetamido-5-(2,3-dihydroxy n-propylcarbamoyl)-2,4,6 of formula (9) - Preparation method of iopromide with triiodobenzoic acid as intermediate. Background technique [0002] Iopromide is a non-ionic iodine-containing contrast agent first developed by Schering, Germany. Its chemical name is: N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo- 5-[(2-methoxyacetyl)amino]-N'-methylphenyl-1,3-carboxamide, the structural formula is: [0003] [0004] It has been widely used in the field of X-ray contrast agents. The preparation method of iopromide reported in the literature is disclosed in US Pat. No. 4,364,921 and PCT Pat. No. WO2009134030. [0005] The relevant preparation method of iopromide reported by U.S. Patent No. 4,364,921, its reaction steps are as shown in reaction scheme 1: [0006] [Reaction Scheme 1] [0007] [0008] According to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C237/46C07C231/14
Inventor 王哲张婷婷熊安伟王林正谢卫陈仕洪
Owner ZHEJIANG STARRY PHARMA
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