Synthesis method of xanthinol nicotinate

A technology of nicotinic acid zantino and a synthesis method, applied in the field of drug synthesis, can solve the problems of low product yield, high toxicity, hindering industrial application and the like, and achieve the effects of simple operation, low toxicity and saving of raw materials

Active Publication Date: 2012-07-25
SHANDONG KEYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the toluene used in this process is a solvent, which is highly toxic, and the product yield in the refining process is low, which hinders industrial application

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] 1. Preparation of the Crude Zantenol Nicotinate

[0022] Add 29.4kg of epichlorohydrin and 12.8kg of absolute ethanol to the chlorine reaction tank, start stirring, and cool down. When the temperature in the tank drops below 20°C, add 25.5kg of N-methylethanolamine dropwise to keep the inner temperature At 18-22°C. After the dropwise addition, keep the reaction at 18-25°C for 2 hours and set aside. Pump 215kg of absolute ethanol into the neutralization tank, start stirring and add 12.1kg of sodium hydroxide to raise the temperature to about 55°C, and slowly add 52.1kg of theophylline. Raise the temperature, and slowly add chlorinated compound dropwise at a uniform speed during reflux. After the addition and heat preservation and reflux for 1.5 hours, cool down and suction filter, pump the filtrate into the reaction tank, heat up to reflux, add 33.8kg of nicotinic acid, and continue to reflux for 30 minutes. After the reaction, the temperature of ice-brine was cooled t...

Embodiment 2

[0026] The synthetic and refining method of nicotinic acid is the same as in Example 1, except that the activated carbon used carries out the following treatments:

[0027] (1) Heat the activated carbon with microwaves, raise the temperature to 190°C at a heating rate of 3°C / min, and treat for 60 minutes;

[0028] (2) Cool the heated activated carbon naturally, put it into PBS buffer, treat it with ultrasonic waves for 2 hours, and dry it at room temperature.

[0029] Among them, the microwave frequency is 10khz, the power is 2kw, during the ultrasonic treatment, 0.2g of activated carbon is added to each milliliter of PBS buffer solution, the ultrasonic treatment is performed intermittently, the continuous time is 4s, the interval is 10s, the ultrasonic frequency is 25khz, and the power is 8kw.

[0030] The components of PBS buffer (pH7.2~7.4) used are: NaCl 137mmol / L, KCl 2.7mmol / L, NaCl 2 HPO 4 4.3mmol / L, KH 2 PO 4 1.4mmol / L.

[0031] The obtained nicotinic acid accou...

Embodiment 3

[0033] The method of Example 1 was used to prepare the crude product of niacin and quinol, except that the following method was used to refine the crude product: the crude product of niacin and 95% ethanol was added to 4 times the mass of 95% ethanol, stirred and refluxed until it was fully dissolved, and the 15wt% dilute hydrochloric acid to adjust the pH of the solution to 2-3, then add 4wt% ordinary activated carbon for decolorization, reflux for 30 minutes and filter to remove the activated carbon, then add the solution to a flash tank for flash evaporation to remove ethanol to obtain niacin The finished product has a yield of 86% and a purity of over 93%.

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Abstract

The invention discloses a synthesis method of xanthinol nicotinate. The synthesis method comprises the following steps: synthesizing 2-hydroxy-3-(2-ethoxy-methylamino) chloropropane by epichlorohydrin and N-methylethanolamine; then reacting the 2-hydroxy-3-(2-ethoxy-methylamino) chloropropane with theophylline and niacin so as to synthesize crude xanthinol nicotinate; and finally, refining the crude xanthinol nicotinate so as to obtain the finished xanthinol nicotinate. The synthesis method is characterized in that solvents used when the 2-hydroxy-3-(2-ethoxy-methylamino) chloropropane is reacted with the theophylline and the niacin are absolute ethyl alcohol. Compared with a mixed solvent of toluene and isopropanol in the prior art, the absolute ethyl alcohol serving as a solvent in the invention has the advantages of cheap price and low toxicity, thereby lightening environmental pressure; and in addition, in the process, the purity and yield of the finished xanthinol nicotinate are improved through an improvement on activated carbon and a refining process. The process has the advantages that the route is clear, the operation is simple, the raw materials are saved and the cost isreduced, thus being beneficial to industrial mass production.

Description

technical field [0001] The invention relates to a method for preparing medicine, in particular to a method for synthesizing zantinoniacin, which belongs to the technical field of medicine synthesis. Background technique [0002] Niacin Zantinol is a xanthine vasodilator that is safe, effective and has few side effects. Its chemical name is 7-[2-hydroxy-3-(2-hydroxyethyl-methylamino)]theophylline nicotinate , the molecular formula is C 13 h 21 N 5 o 4 ·C 6 h 5 NO 2 , the molecular weight is 434.45, and the molecular structure formula is: [0003] . [0004] Niacin can directly act on the smooth muscle of small arteries and capillaries to dilate blood vessels, improve blood rheology, reduce the resistance of peripheral blood vessels, promote glucose to pass through the blood-brain barrier, and enhance the utilization of glucose and oxygen in brain cells. Improves glucose metabolism and brain function in the brain. It also has the effect of promoting fat metabolism,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D473/04C07D213/80
Inventor 陈广岭张彭魏乐坤白磊
Owner SHANDONG KEYUAN PHARMA
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