356783-16-9Relevant articles and documents
PROCESS FOR THE PREPARATION OF 3,6-DICHLOROCYANO PYRAZINE, 3,6-DIOXOPIPERAZINE DERIVATIVES AND PRODUCTION OF FAVIPIRAVIR THEREOF
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Paragraph 0038; 0053-0054, (2021/12/31)
The present invention relates to a method of preparing derivatives of 3,6-dichlorocyano pyrazine, 3,6-dioxopiperizin and the production of favipiravir by cyclization and chlorination mediated by ammonia or amine using POCl3 in the presence of pyridine or PCl5. [Formula] In derivatives of 3,6-dioxopiperazine (III), X represents CN, CONH2 or COOR2', R1, R 2 and R2' are individually selected from H, alkyl C1-C12, COOR3 and SO2R3, R 3 being a linear or branched lower alkyl substituted or unsubstituted.
Favipiravir intermediate 3, 6-dichloro-2-cyanopyrazine synthesis process
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Paragraph 0014; 0043; 0045-0059, (2021/07/17)
The present invention relates to a favipiravir intermediate 3, 6-dichloro-2-cyanopyrazine synthesis process, which is characterized in that the synthesis route is as follows as described in the specification. The cheap 2-chloropyrazine is used as the raw material, the product 3, 6-dichloro-2-cyanopyrazine can be obtained only through two-step reaction, the total yield is 55% or above, all the used reagents can be common reagents which can be purchased commercially, the production cost is reduced, and a synthesis process for large-scale industrial production of the 3, 6-dichloro-2-cyanopyrazine is achieved. According to the method disclosed by the invention, the synthesis process conditions are optimized, and particularly, the catalyst and the cocatalyst in the step (2) are selected, so that the yield and the purity of the product are further improved.
Favipiravir intermediate and synthesis method of favipiravir
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Paragraph 0060; 0061, (2020/08/12)
The invention discloses a favipiravir intermediate and a synthesis method of favipiravir. The synthesis method comprises the following steps: taking 2,5-dihalopyrazine as an initial raw material, reacting 2,5-dihalopyrazine with formamide under the action of an oxide and a catalyst to generate 6-halo-3-chloro-2-amide pyrazine; carrying out a reaction on 6-halo-3-chloro-2-amide pyrazine under the action of a dehydration chlorinating agent and an acid-binding agent to generate a favipiravir intermediate 3,6-dichloro-3-cyanopyrazine; carrying out an aromatic ring fluorination reaction on the obtained favipiravir intermediate and potassium fluoride in dimethyl sulfoxide to generate 3,6-difluoro-3-cyanopyrazine; adding the 3,6-difluoro-3-cyanopyrazine into a water solution containing sodium acetate, and carrying out hydrolysis to obtain 6-fluoro-3-hydroxyl-2-cyanopyrazine; and finally, carrying out a cyano hydrolysis reaction to obtain favipiravir. A mixture of 2,5-dichloropyrazine and 2-chloro-5-bromopyrazine are used as raw materials to synthesize the favipiravir intermediate, the raw material cost is remarkably reduced, and the provided synthesis method has the technical advantages of high yield and low cost.