Method used for preparing 4-chloropyrrolo[2,3-d]pyrimidine

Abstract

The invention discloses a novel method used for preparing high-purity 4-chloropyrrolo[2,3-d]pyrimidine in industrialization scale. According to the method, ethyl cyanoacetate, bromo-acetal, formamidine acetate, and sodium alcoholate are taken as raw materials; N,N-dimethylformamide, ethyl alcohol, and phosphorus oxychloride are taken as solvents; and 4-chloropyrrolo[2,3-d]pyrimidine is obtained via three-step approach. The process route of the method is simple; time is short; next step feed can be carried out directly without complex purification process of intermediates; no toxic agent is used; the method is safe and reliable, and is low in cost; total yield is higher than 30%; and the purity of obtained products is as high as 99.2%.

Description

[0001] technical field

[0002] The invention belongs to the field of organic chemistry and relates to a method for industrially preparing high-purity 4-chloropyrrolo[2,3-d]pyrimidine. Background technique

[0003] 4-Chloropyrrole[2,3-d]pyrimidine is an important pharmaceutical and chemical intermediate used in the preparation of the anti-rheumatic arthritis drug Tofacitinib.

[0004] In 2007, Mibenmei et al. disclosed a method for the gram-scale synthesis of 4-chloropyrrole[2,3-d]pyrimidine in "Chemical Reagents". The first step needs to be purified by high vacuum fractionation to obtain 2-cyano Base-4,4-diethoxybutyric acid ethyl ester makes it difficult to scale up the process. In the second and third steps, a large amount of high-risk metal sodium and Raney nickel are used. A total of 5 steps are required, and the steps are lengthy Complexity, long preparation period, and high potential safety hazards in the process, it is difficult to apply it in production. Patent CN...

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