Synthesis Of Antidiabetic Drug Interme Diates5-chloropyrazine-2-carboxylic Acid And Its Derivatives

In recent years, many chemical structure of the new anti-diabeticdrugs contains5-chloropyrazine-2-carboxylic acid structure and itsderivatives, for example: glucokinase activators, melanin-concentratinghormone receptor antagonist, Beta-site APP cleaving enzyme2inhibitorsand so on. For this reason,5-chloropyrazine-2-carboxylic acid and itsderivatives as important intermediates for these new anti-diabetic drugs arereceiving more and more attention in recent years. Thus, the study of5-chloropyrazine-2-carboxylic acid and its derivatives can providetheoretical and practical value for a new generation of anti-diabetic drugswhich contain5-chloropyrazine-2-carboxylic acid and its derivativesstructure.Under the principle of the convenient and cheap to get raw materials,easy to operate, safe and reliable to produce, we referred to the relevantliterature and decided to use the inverse synthetic analysis to synthetise5-clopyrazine-2-carboxylic acid from the starting materialsroute2-acetylfuran. On the basis of the synthetic method, six related derivatives weregathered, and the main results are as follows: 1. A new a four-step reaction synthesis of5-Chloropyrazine-2-carboxylic acid was established, which used2-acetyl furan as startingmaterial, oxidated by selenium dioxide, cyclized by glycine amide,chlorinate by phosphorus oxychloride,oxidated by potassiumpermanganate. The route has merit of the cheap raw materials, mildreaction conditions and simple operation.2. In the cyclization reaction, the optimal synthesis conditions usingorthogonal experiment method makes the step to improve the reaction yieldof23.1%compared to the literature.3. In the synthesis of5-chloropyrazine-2-carboxylic acid, theinnovative method of using hydrochloric acid extracting with ethyl acetate,instead of the expensive strongly acidic cation exchange column, reducedthe manufacturing cost.4. The synthesis not only gathered5-chloropyrazine-2-carboxylicacid but also received six5-chloropyrazine-2-carboxylic acidderivatives.In summary, this article reports a new a synthesis route of5-Chloropyrazine-2-carboxylic acid was established, which used2-acetylfuran as starting material, oxidated by selenium dioxide, cyclized byglycine amide, chlorinate by phosphorus oxychloride,oxidated bypotassium permanganate. The route has merit of the cheap raw materials,mild reaction conditions and simple operation. The synthesis gathered5- chloropyrazine-2-carboxylic acid and six5-chloropyrazine-2-carboxylic acid derivatives. The route lay a foundation for the study ofnovel anti-diabetic drugs and has a certain theoretical and practicalsignificance.