Preparation method of pentoxifylline impurity

A technology of pentoxifylline and theobromine, applied in the direction of organic chemistry and the like, can solve the problems of high price, long supply cycle, failure to find the preparation method of impurity E and impurity K, etc.

Pending Publication Date: 2021-04-30
赤峰经方医药技术开发有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, obtaining impurity E and impurity K through commercial channels is not only expensive, but also has a very long delivery cycle. Through literature research, no preparation method for impurity E and impurity K has been found. Considering the demand and supply of such impurities, It is of practical significance to develop the preparation methods of impurity E and impurity K

Method used

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  • Preparation method of pentoxifylline impurity
  • Preparation method of pentoxifylline impurity
  • Preparation method of pentoxifylline impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] At room temperature, add 50mL of N,N-dimethylformamide into a 100mL three-necked flask, start stirring, add 9.0g of theobromine, 10.6g of sodium carbonate, raise the temperature to 70°C, add 4.5g of dibromomethane dropwise, complete the addition, and keep warm Continue to stir at 70°C for 4h, stop the reaction, cool, filter, pour the residue into 200mL water, stir, add 2N sodium hydroxide to adjust the pH to 10-11, filter, filter out insoluble matter, add 100mL ethyl acetate to the filtrate to extract, organic Separate the phases, add 50 mL of water to wash, add 5.0 g of anhydrous sodium sulfate to the organic phase, dry for 30 min, filter, and evaporate the organic phase to dryness to obtain a white solid, which is purified by column chromatography to obtain 7.0 g of a white solid, with a yield of 75.3%. .

[0025] 1 H-NMR (500MHz, DMSO-D6): δ7.86(s, 2H), 5.02(s, 2H), 3.68(s, 6H), 3.32(s, 6H); HRMS: m / z=373.1295[M +1] + .

Embodiment 2

[0027] At room temperature, add 50 mL of N,N-dimethylacetamide into a 100 mL three-necked flask, start stirring, add 9.0 g of theobromine, 10.4 g of potassium carbonate, raise the temperature to 80°C, add 7.0 g of diiodomethane dropwise, and complete the addition. Insulate at 80°C and continue to stir for 2 h, stop the reaction, cool, filter, pour the residue into 200 mL of water, stir, add 2N sodium hydroxide to adjust the pH to 10-11, filter, filter out insoluble matter, add 100 mL of ethyl acetate to the filtrate for extraction, The organic phase was liquid-separated, washed with 50 mL of water, the organic phase was dried by adding 5.0 g of anhydrous sodium sulfate for 30 min, filtered, and the organic phase was evaporated to dryness to obtain a white solid, which was subjected to column chromatography (ethyl acetate:n-hexane=1:5 ~1:3, v / v) to obtain 7.5 g of white solid with a yield of 80.6%.

Embodiment 3

[0029] At room temperature, add 40 mL of tetrahydrofuran and 10 mL of water into a 100 mL three-necked flask, start stirring, add 9.0 g of theobromine, 2.2 g of sodium hydroxide, and dropwise add 7.0 g of diiodomethane. Cool, filter, pour the residue into 200mL water, stir, add 2N sodium hydroxide to adjust the pH to 10-11, filter, filter out insoluble matter, add 100mL dichloromethane to the filtrate for extraction, separate the organic phase, add 50mL water to wash, The organic phase was dried by adding 5.0 g of anhydrous sodium sulfate for 30 min, filtered, and the organic phase was evaporated to dryness to obtain a white solid, which was purified by column chromatography to obtain 6.8 g of a white solid with a yield of 73.1%.

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Abstract

The invention discloses a preparation method of a pentoxifylline impurity. The preparation method comprises the following steps: adding theobromine into an organic solvent, stirring, and adding a certain amount of alkali; slowly dropwise adding a halogenating reagent into a reaction system for reaction under a temperature control condition; after the reaction is finished, filtering the reaction liquid, adding alkali liquor into the obtained filtrate to adjust the pH value to 10-11, adding a solvent for extraction, and separating the liquid; and washing, drying, concentrating and purifying the organic phase to obtain a target product. The method is easy to operate and can be used for quickly preparing the high-purity pentoxifylline impurity.

Description

technical field [0001] The application belongs to the field of chemical pharmacy, and relates to a method for preparing chemical drug pentoxifylline-related impurities. Background technique [0002] Pentoxifylline (Pentoxifylline) is a vasodilator drug, mainly used in the early stage to improve the circulation after ischemic stroke, to improve the brain, peripheral blood vessels, ear and eye internal circulation disorders, increase the blood supply of the above tissues, improve It is used in the treatment of various clinical symptoms such as transient ischemic attack, sequelae of stroke, cerebral dysfunction caused by cerebral ischemia, thromboembolic vasculitis, and sudden deafness. From the pharmacological point of view, pentoxifylline can independently reduce the viscosity of blood, increase the degeneration of red blood cells, improve the hemorheological characteristics of white blood cells, and can inhibit the adhesion and activation of neutrophils, increase blood flow,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D519/00
CPCC07D519/00
Inventor 张丽华
Owner 赤峰经方医药技术开发有限责任公司
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