Preparation method of 6-(3-chloropropyl)amino-1,3-dimethyluracil

A technology of dimethyluracil and dimethyluracil, which is applied in the field of preparation of 6-amino-1,3-dimethyluracil, can solve the pressure of increasing the cost of labor protection and environmental protection, and increase the synthesis of drugs And drug quality analysis cost, human and environmental hazards and other issues, to achieve the effect of cheap raw materials, green and safe synthesis process, and cost reduction

Inactive Publication Date: 2021-09-17
沈阳信康药物研究有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] There is no report about solvent-free in the chlorination step of existing technology, all is to have the reaction that solvent participates in, and the solvent used is except 1,2-ethylene dichloride, also has chloroform (Zhou Junhong. Crystal form analysis [D]. Tianjin: Tianjin University, 2007), wherein 1,2-dichloroethane and chloroform are used as solvents for the chlorination reaction. Due to the high boiling point, it is difficult to remove, and more importantly, it is a known A class of solvents that can be carcinogenic and harmful to humans and the environment, and the quality standards of urapidil raw materials require analysis of the residual solvent of 1,2-dichloroethane in the later stage, which not only increases the cost of drug synthesis and drug quality analysis, At the same time, it also increases the cost of labor protection and the pressure on environmental protection

Method used

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  • Preparation method of 6-(3-chloropropyl)amino-1,3-dimethyluracil

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Effects of different molar ratios of 6-(3-hydroxypropyl)amino-1,3-dimethyluracil II to thionyl chloride on product yield and purity:

[0022]

[0023] Carry out the reaction according to the above reaction equation, change the molar ratio of 6-(3-hydroxypropyl)amino-1,3-dimethyluracil II to thionyl chloride, fix the reaction temperature at 50°C, and the reaction time for 2 hours. After the end, the excess thionyl chloride was directly distilled off under reduced pressure at 45° C. (thionyl chloride can be recovered and reused). Then add 95% acetone pre-cooled to 5-15°C, cool down to below 0°C, keep stirring for 2 hours, and filter with suction. Rinse with 95% acetone and air-dry at 70°C for 10-12h.

[0024] The results are shown in Table 1:

[0025] Table 1

[0026]

[0027]

Embodiment 2

[0029] The preparation method is as in Example 1, the molar ratio of fixed 6-(3-hydroxypropyl)amino-1,3-dimethyluracil II to thionyl chloride is 1:3, the reaction time is 0.5 hours, and the post-treatment method As in Example 1, the impact of different reaction temperatures on product yield and purity.

[0030] The results are shown in Table 2:

[0031] Table 2

[0032]

Embodiment 3

[0034] The preparation method is as in Example 1, the molar ratio of immobilized 6-(3-hydroxypropyl)amino-1,3-dimethyluracil II to thionyl chloride is 1:3, the temperature is 50°C, and the post-treatment method As in Example 1, the impact of different reaction times on product yield and purity.

[0035] The results are shown in Table 3:

[0036] table 3

[0037]

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Abstract

The invention belongs to the technical field of drug synthesis processes, and provides a preparation method of 6-(3-chloropropyl)amino-1,3-dimethyluracil. 6-(3-hydroxypropyl)amino-1,3-dimethyluracil is used as a raw material, and 6-(3-chloropropyl)amino-1,3-dimethyluracil is obtained by chlorination with thionyl chloride. According to the reaction, thionyl chloride is directly used as a reaction reagent and solvent, the yield can reach 85% or above, the highest yield can reach 90% or above, and the highest purity can reach 98% or above. Compared with the prior art, the method has the advantages that the yield and the purity are obviously improved, the post-treatment is convenient, the post-treatment solvent can be recycled, and more importantly, the use of 1,2-dichloroethane which is carcinogenic and harmful to human and environment is avoided. When the method is used for synthesizing an antihypertensive drug urapidil, not only are the types of solvents reduced, but also the analysis of a 1,2-dichloroethane residual solvent in the drug quality analysis is avoided, and the method is a green and safe preparation method which is very suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis technology, and in particular relates to a preparation method of 6-(3-chloropropyl)amino-1,3-dimethyluracil. Background technique [0002] 6-(3-Chloropropyl)amino-1,3-dimethyluracil is a very important intermediate in the synthesis of antihypertensive drug urapidil. [0003] The chemical structure of urapidil is not similar to that of prazosin. It has the effect of blocking postsynaptic receptors and blocking peripheral α2 receptors, but the former is the main one. In addition, it has the effect of activating the central serotonin 1A receptor, which can reduce the sympathetic feedback of the medullary cardiovascular regulation center and play a role in lowering blood pressure. The relaxation effect of this product on veins is greater than that on arteries, and it does not affect intracranial blood pressure when lowering blood pressure. This product can still reduce cardiac preload and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/545
CPCC07D239/545
Inventor 唐星陈国良黄浩于叶玲李腾飞
Owner 沈阳信康药物研究有限公司
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