Title:
LOW-COST PREPARATION METHOD FOR PALBOCICLIB
Document Type and Number:
WIPO Patent Application WO/2023/035667
Kind Code:
A1
Abstract:
Disclosed is a low-cost preparation method for palbociclib. The method comprises: taking 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester as an initial raw material, taking large-steric-hindrance alkali as an acid-binding agent, performing a nucleophilic substitution reaction with a compound represented by formula 3, and performing post-treatment, quenching and dealkalizing to obtain a large-particle compound represented by formula 4; then taking n-butyl alcohol and water as solvents, taking diisopropylethylamine as an acid-binding agent and a protective agent, and under the action of a composite catalyst palladium chloride and cuprous iodide, performing a Herk alkylation reaction with n-butyl vinyl ether; and under the protection of an organic alkali, refining by means of an ester solvent to obtain a high-purity compound represented by formula 5 with high yield, and hydrolyzing the compound represented by formula 5 by means of a mixed solvent of n-butyl alcohol, anisole and water under an acidic condition to obtain a finished product of palbociclib. The method greatly reduces the usage amount of a palladium catalyst, and is simple and convenient to operate, less in environmental pollution, high in yield, high in product quality and more suitable for industrial production.
Inventors:
LI TAITONG (CN)
SU MAN (CN)
ZHANG QINGTAO (CN)
LIU ZHONGHUA (CN)
HU XIUKANG (CN)
SU MAN (CN)
ZHANG QINGTAO (CN)
LIU ZHONGHUA (CN)
HU XIUKANG (CN)
Application Number:
PCT/CN2022/094111
Publication Date:
March 16, 2023
Filing Date:
May 20, 2022
Export Citation:
Assignee:
SHANDONG BOYUAN PHARMACEUTICAL CO LTD (CN)
International Classes:
C07D471/04
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Attorney, Agent or Firm:
JINAN CHENGZHI TRADEMARK & PATENT OFFICE CO., LTD. (CN)
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