Synthesis process of crizotinib intermediate

Abstract

The invention discloses a synthesis process of a crizotinib intermediate. The synthesis process comprises the following steps: with 2,6-dichloro-3-fluoroacetophenone as the raw material in an alkali and solvent environment and hydrogen as a reducing agent, reacting under the action of a chiral catalyst to obtain (R)-1-(2,6-dichloro-3-fluorophenyl)ethyl alcohol; the high-chiral-purity crizotinib intermediate is obtained at one step as the process adopts the reduction system, the complex chiral resolution process of the existing process is omitted, the period of the process is greatly shortened,the production cost is low, the reaction condition is mild, the process is stable, the conversion rate is high, the environment pollution caused by the reaction is small, and the synthesis process isfavorable for realizing the industrial production.

Description

technical field

[0001] The invention belongs to the field of synthesis of pharmaceutical and chemical intermediates, and mainly relates to a synthesis process of a crizotinib intermediate. Background technique

[0002] Crizotinib (Crizotinib, English trade name Xalkori), chemical name: (R)-3-[1-(2,6-dichloro-3-fluoro-benzene)-ethoxy]-5-(1- Piperidine-4-alkyl-1hydro-pyrazole-4-alkyl)-pyrimidine-2-indan is an ATP-competitive multi-target protein kinase inhibitor developed by Pfizer that inhibits Met / ALK / ROS. It has been confirmed that crizotinib has a significant clinical effect on humans in tumor patients with abnormal activity of ALK, ROS and MET kinases. The structural formula of crizotinib is as follows:

[0003]

[0004] Crizotinib is one of the fastest drugs in the history of cancer drug development. It caused a sensation after it was launched in the United States in 2011. The inventor is Chinese scientist Dr. Cui Jingrong (US patent 7858643), who won the 38th US N...

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