Method for preparing Ibrutinib
Abstract:
Provided is a method for preparing Ibrutibin (I), and steps of preparing same comprise: 4-benzyloxybenzoyl chloride (II) is used as a raw material, condensation and methoxidation reactions occur among 4-benzyloxybenzoyl chloride (II), malononitrile, and dimethyl sulfate to generate 4-benzyloxyphenyl(methoxy)vinylidenedicyanomethane (III), pyrazole cyclization occurs between the intermediate (III) and 1-(3R-hydrazino-1-piperidino)-2-propylene-1-ketone (IV) to acquire 1-[(3R)-[3-(4-benzyloxyphenyl)-4-nitrile-5-amino-1H-pyrazole]-1-piperidino]-2 propylene-1-ketone (V), and pyrimidine cyclization occurs between an intermediate (V) and a cyclizing agent to prepare Ibrutinib (I). In the preparation method, the raw material is readily available, and the process is simple, economical, environmentally friendly, and is suitable for industrial production.
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