Preparation method of Avopan and intermediate thereof

Abstract

The invention provides a preparation method of Avopan and an intermediate thereof, and relates to the technical field of organic synthesis. The preparation method of the Avopan intermediate as shown in a formula (IV) comprises the step of carrying out transamination reaction on a compound as shown in a formula (V) and isopropylamine or salt thereof, wherein the transamination reaction is carried out under the catalysis of [omega]-transaminase and pyridoxal phosphate. In the preparation method disclosed by the invention, asymmetric transamination reaction of the compound shown in the formula (V) is catalyzed by the [omega]-transaminase and the pyridoxal phosphate, selectivity is very high,hardly any diastereoisomer is generated, ee% (excessive enantiomer) is greater than 98.0%, the reaction yield is greater than 80%, purification cost in production is reduced, atom economy is high, and good industrial application prospects are realized.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of Avacopan and its intermediate. Background technique [0002] The complement system plays a very important role in the immune response to clear the source of infection, foreign antigens, virus-infected cells and tumor cells. But inappropriate or excessive activation of the complement system can lead to severe inflammation and tissue destruction, and these results can even be life-threatening. These consequences are manifested clinically in various diseases, including transplant rejection, nephritis, pathological inflammation, and autoimmune diseases (the role of the complement system in trauma and infection, "International Journal of Surgery", 1993, No. 17 -18). [0003] Activation of the complement pathway produces biologically active fragments of complement proteins. For example, C3a, C4a and C5a hypersensitive response protein and C5b-9 memb...

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Problems solved by technology

[0012] Among the above three methods, the first method is similar to the second method, but the reaction sequence is different. Both methods involve chiral prosthetic groups, and the atom economy is relatively low; and the hydrogenation reaction catalyzed by palladium is not very It is selective and needs to resolve and enrich the chiral isomers, which will lead to the reduction of the purity and yield of the target product, so the cost of both preparation methods is high

The third method, involving palladium-catalyzed Suzuki reaction, platinum-catalyzed hydrogenation reaction, has low atom economy and is not suitable for industrial production

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