4-chloro pyrrolo[2,3-d]pyrimidine substituted compound and synthetic method thereof

Abstract

The invention relates to a method for synthesizing 4-chloro pyrrolo[2,3-b] pyridine. The method mainly comprises three steps: 1) carrying out p-toluenesulfonyl chloride protection on a 4-chloro pyrrolo[2,3-d]pyrimidine compound; 2) reacting the 4-chloro pyrrolo[2,3-d]pyrimidine compound protected by p-toluenesulfonyl chloride (Ts) with a compound to be substituted; and 3) carrying out Ts protecting group removal on the substituted compound obtained in the step 2 to obtain the target product. The 4-chloro pyrrolo[2,3-d]pyrimidine substituted compound obtained through a three-step chemical reaction process has a kinase inhibition effect, and is an important process for synthesizing a drug intermediate.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a 4-chloropyrrole[2,3-d]pyrimidine substituted compound and a synthesis method thereof. Background technique [0002] Pyrrole[2,3-d]pyrimidine is an important anticancer drug lead compound structure molecule, which plays an important role in the treatment of cancer, inflammatory diseases and autoimmune diseases. The compound itself is an effective protease inhibitor A large number of protease inhibitor molecules can be derived during structural modification. In previous reports, the ammonia water substituted 4-chloropyrrole [2,3-d] pyrimidine compound can effectively inhibit the activity of JAK3 kinase protein, so as to achieve The effect of treating autoimmune diseases, and can also be used to treat skin diseases, and pyrrole [2,3-d] pyrimidine compound molecules are also widely used in anti-tumor treatment, antibacterial and other aspects of treatment, and are importa...

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Problems solved by technology

[0003] Regarding the synthesis method of pyrrole[2,3-d]pyrimidine substituted compounds, the patent application number: 201510163913.X reports the synthesis of substituted pyrrole[2,3-d]pyrimidines with aminopyrrole[2,3-d] Pyrimidine, the inventor of the patent carried out the reaction of ammonia water and chloropyrrole [2,3-d] pyrimidine through a one-step method according to the ratio of 2 to 20:1 at a temperature of 0 to 70°C for 5 to 20 hours. Although this method A higher yield product is obtained by a one-step method, but the chemoselectivity is poor. The active group of chloropyrrole[2,3-d]pyrimidine includes the chlorine atom connected to the pyrimidine ring and the hydrogen atom on the pyrrole ring. Therefore, when ammoniacal liquor reacts chemically with chloropyrrole [2,3-d] pyrimidine compound, there are more by-products, and when reacting, the consumption of ammoniacal liquor is 2 times that of chloropyrrole [2,3-d] pyrimidine compound ~20 times, it is also a waste in terms of the amount of reactants. Secondly, in terms of impurity removal of the final product, the volatilization of ammonia water is also a pollution of the environment, and affects the purity of the target product at the same time

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