Preparation method for high-purity gliclazide intermediate namely p-toluenesulfonylurea

A technology for tosyl urea, crude tosyl urea, applied in the field of pharmaceutical chemical synthesis, can solve the problems of restricting the production and development of tosyl urea products, having a purity of only 98%, low product quality and the like, achieving mild conditions and easy Storage, high purity effect
CN110372545AActive Publication Date: 2019-10-25山东海佑福瑞达制药有限公司
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
山东海佑福瑞达制药有限公司
Publication Date
2019-10-25

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Abstract

The invention discloses a simple and convenient preparation method for p-toluenesulfonylurea. The preparation method comprises the following reaction steps: according to a reaction flow as shown in aformula 3 which is described in the specification, filling a reaction container with nitrogen gas to replace air in the reaction container, then adding an organic solvent and p-toluenesulfonyl isocyanate, then charging ammonia gas, carrying out a reaction at a low temperature under stirring so as to generate a crude p-toluenesulfonylurea product, then carrying out filtering, adding acetonitrile / water for refluxing, carrying out programmed cooling (10 DEG C / h), and carrying out centrifuging and drying so as to obtain a white crystal, namely, the p-toluenesulfonylurea. The preparation method provided by the invention prepares the p-toluenesulfonylurea by ammonolysis of the p-toluenesulfonyl isocyanate with the ammonia gas in toluene and can reach a yield up to 96.3%; and a product has a purity of 99.9% or more, is a white crystalline solid and is free of impurities. The preparation method provided by the invention has the following advantages: operation is simple and convenient; conditions are mild; post-treatment is easy; and a product has high purity and high yield, is a white crystal and facilitates storage.
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Description

technical field

[0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a convenient preparation method of p-toluenesulfonylurea. Background technique

[0002] P-toluenesulfonylurea can be used to synthesize hypoglycemic drug Gliclazide (Gliclazide) and so on. There are many reports on the synthesis methods of p-toluenesulfonylurea. Literature reports mainly use p-toluenesulfonamide and p-toluenesulfonyl chloride as starting materials. For example, Chinese patent CN201210012306.X discloses a preparation method of p-toluenesulfonylurea shown in formula 1, using p-toluenesulfonamide It is produced by condensation with urea. The post-treatment of this method is cumbersome, the required temperature is too high, and the product quality is poor, and the yield is only 75.2%.

[0003]

[0004] And the Mannich-like reaction research report of the sulfonylurea shown in formula 2 is obtained by reacting p-toluenesulfonyl chlorid...

Claims

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