Method for synthesizing Eltrombopag using microchannel reactor

Abstract

The invention discloses a method for synthesizing Eltrombopag by using a microchannel reactor. The method includes the following steps: S1, material synthesis: adding the raw material 3,4-dimethylaniline into the acid aqueous solution, and the dissolved material is a Dissolving sodium nitrite in water to obtain material two, dissolving sodium bisulfite and sodium hydroxide in water to obtain material three, the solution made of hydrochloric acid and water is material four, and the raw material 3-amino-2 hydroxyl-[ 1,1-biphenyl]-3 formic acid is added to the acid aqueous solution, and the material five is obtained by dissolving, and the sodium nitrite is dissolved in water to obtain the material six; S2, the material is passed into the microchannel reactor S3, and the first intermediate 3,4 is obtained ‑Dimethylphenylhydrazine hydrochloride, reacted with ethyl acetoacetate to give the second intermediate 2‑(3,4‑dimethylphenyl)‑5‑methyl‑1H‑pyrazole‑3(2H)‑ Ketone; S4, material five and material six are passed into the microchannel reactor to react, and the reaction solution flowing out directly flows into the 2-(3,4-dimethylphenyl)-5-methyl-1H-pyrazole ‑3(2H)‑ketone solution in the reaction flask, to obtain Eltrombopag.

Description

technical field [0001] The invention belongs to the field of drug synthesis in organic synthesis, and in particular relates to a method for synthesizing Eltrombopag by using a microchannel reactor. Background technique [0002] Eltrombopag was developed by GlaxoSmithKline in the UK and was approved by the US FDA in November 2008 for marketing in the US. Eltrombopag is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpura and in patients who do not respond well to corticosteroids, immunoglobulins, or splenectomy. Eltrombopag is the first oral non-peptide thrombopoietin receptor agonist approved for the treatment of adults with chronic ITP. Preclinical and clinical studies have shown that stimulating this product can increase the proliferation and differentiation of bone marrow megakaryocytes in platelets. Its chemical name is 3'-{(2Z)-2-[1-(3,4-xylyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazole-4...

AI Technical Summary

Problems solved by technology

[0006] Thus, the synthesis of Eltrombopag and its intermediates in the prior art are all synthesized by the traditional still-type diazotization process, but the traditional still-type diazotization process has certain dangers. Slightly higher or under the action of light, especially diazonium salts containing nitro groups are easy to decompose, and some can even decompose at room temperature

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