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A kind of preparation method of 4-amino-2,6-dimethoxypyrimidine

A technology of dimethoxypyrimidine and methoxy, which is applied in the field of preparation of 4-amino-2,6-dimethoxypyrimidine, can solve a large number of colored phosphorus-containing waste water, the intermediate products are easily hydrolyzed and ring-opened, and the yield is reduced. rate and other issues, to achieve the effect of simplifying the production process, improving productivity and selectivity, and major social benefits

Active Publication Date: 2021-08-24
NANJING TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the one hand, the intermediate product of this method is very easy to hydrolyze and open the ring, reducing the yield
On the other hand, this method also uses the toxic chlorinating agent phosphorus oxychloride, which will produce the by-product 4-amino-2,6-dichloropyrimidine phosphoryl dichloride which is explosive in contact with water
Moreover, a large amount of colored phosphorus-containing wastewater will be produced during the synthesis process, so it is very meaningful to develop a new green and environmentally friendly process route

Method used

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  • A kind of preparation method of 4-amino-2,6-dimethoxypyrimidine
  • A kind of preparation method of 4-amino-2,6-dimethoxypyrimidine
  • A kind of preparation method of 4-amino-2,6-dimethoxypyrimidine

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Using o-methylisourea bisulfate and methyl cyanoacetate as raw materials

[0035] Step 1. In a 100mL three-necked flask, add 12mmol of o-methylisourea bisulfate, dissolve 20mL of methanol and heat and stir. When the temperature reaches 60°C, add 10mmol of methyl cyanoacetate, and keep warm at 60°C for 3 hours. After the heat preservation is complete, Control the distillation temperature to 40°C, distill methanol at normal pressure first, then distill under negative pressure until the negative pressure is -0.08MPa, until there is no distillate, 1.25g of light yellow powder N'-ethylcyanocarbonyl-O-methyliso urea.

[0036] Step 2. Take 10mmol (1.29g) of the light yellow powder obtained in step (1), add 3mmol potassium carbonate, 0.8mmol tetrabutylammonium bromide and 10mmol dimethyl sulfate, and dissolve in 20mL acetone. Then reflux reaction at 50°C for 5h, after the heat preservation was completed, the temperature was lowered to 30°C, and filtered. Control the distillat...

Embodiment 2

[0041] Using o-methylisourea hydrochloride and methyl cyanoacetate as raw materials

[0042] Step 1. In a 100mL three-necked flask, add 15mmol o-methylisourea hydrochloride, dissolve in 20mL methanol, heat and stir, add 10mmol methyl cyanoacetate when the temperature reaches 70°C, keep warm at 70°C for 5h, keep warm After that, control the distillation temperature to 80°C, first distill methanol under normal pressure, and then distill under negative pressure until the negative pressure is -0.08MPa, until there is no distillate, 1.23g of light yellow powder N'-ethylcyanocarbonyl-O-methanol is obtained. isourea.

[0043] Step 2. Take 10mmol (1.29g) of the light yellow powder obtained in step (1), add 5mmol potassium carbonate, 0.8mmol tetrabutylammonium bromide and 12mmol dimethyl sulfate, dissolve in 20mL acetone, and then reflux at 60°C After 6 hours, heat preservation is completed, cool down to 40°C, and filter. Control the distillation temperature to 40°C, distill acetone ...

Embodiment 3

[0048] Using o-methylisourea nitrate and methyl cyanoacetate as raw materials

[0049] Step 1. In a 100mL three-necked flask, add 18mmol of o-methylisourea nitrate, dissolve in 20mL of methanol and heat and stir. When it reaches 70°C, add 10mmol of methyl cyanoacetate, and keep warm at 70°C for 6h. After the heat preservation is complete, control The distillation temperature is 80°C, distill methanol at normal pressure first, then distill under negative pressure until the negative pressure is -0.08MPa, and until there is no distillate, 1.21g of light yellow powder N'-ethylcyanocarbonyl-O-methyliso urea.

[0050] Step 2. Take 10mmol (1.29g) of the light yellow powder obtained in step (1), add 8mmol potassium carbonate, 1mmol tetrabutylammonium bromide and 16mmol dimethyl sulfate, and dissolve in 20mL acetone. Then reflux reaction at 70°C for 6h, after the heat preservation was completed, the temperature was lowered to 50°C, and filtered. Control the distillation temperature t...

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Abstract

The invention relates to a preparation method of 4-amino-2,6-dimethoxypyrimidine. The method uses o-methylisourea salt and cyanoacetate as raw materials, undergoes condensation, methylation, and self-cyclization to generate 4-amino-2,6-dimethoxypyrimidine. The invention not only simplifies the production process, optimizes the reaction conditions, improves the yield and selectivity of the reaction, but also solves the problem that the original process will produce a large amount of colored phosphorus-containing waste water, and provides a new method for industrial production of 4-amino-2,6 ‑Dimethoxypyrimidine offers a green and viable route. The structural formula of 4-amino-2,6-dimethoxypyrimidine is as follows:

Description

technical field [0001] The invention relates to an organic synthesis method, in particular to a preparation method of 4-amino-2,6-dimethoxypyrimidine. Background technique [0002] 4-Amino-2,6-dimethoxypyrimidine is an important pharmaceutical intermediate, which can be used in the synthesis of long-acting sulfa drug-sulfadimethoxine. This drug is particularly effective for infections of the upper respiratory tract and urinary tract, and has very slight irritation to the kidneys, with low side effects. As a long-acting sulfa drug with excellent performance, the concentration of sulfadimethoxine in the blood can be maintained for a long time, so the frequency and dosage of administration can be greatly reduced. [0003] There are mainly two mature synthesis techniques for 4-amino-2,6-dimethoxypyrimidine. The first is the barbituric acid method, using barbituric acid as the raw material, phosphorus oxychloride as the chlorinating agent, chlorination, ammoniation, and methoxy...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/52
CPCC07D239/52
Inventor 管国锋丁靖黄武万辉杨南松赵云德郭恒和
Owner NANJING TECH UNIV