Continuous low-cost preparation method of ibrutinib

The invention discloses a continuous low-cost preparation method of ibrutinib, belonging to the technical field of medicine synthesis. The method comprises the following steps: 1) carrying out a Mitsunobu reaction on a raw material, DIAD and triphenylphosphine to obtain an intermediate; 2) removing...

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Hauptverfasser: LIU DONGNA, ZHENG XIANGZHANG, LIU YANJUN, LIANG BINGCHEN, LIU ZHENQIANG, LIU XINYUAN, WANG YUDONG
Format: Patent
Sprache:chi ; eng
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Zusammenfassung:The invention discloses a continuous low-cost preparation method of ibrutinib, belonging to the technical field of medicine synthesis. The method comprises the following steps: 1) carrying out a Mitsunobu reaction on a raw material, DIAD and triphenylphosphine to obtain an intermediate; 2) removing a Boc protecting group from a reaction solution, extracting unreacted 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine, and feeding and applying the unreacted 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine indiscriminately; 3) adding dichloromethane into a water phase obtained afterraw material extraction in the step 2), adjusting a pH value by using an aqueous sodium hydroxide solution, separating out an organic phase, carrying out drying by using anhydrous sodium sulfate, anddirectly adding triethylamine and acryloyl chloride for an acylation reaction; and 4) conducting washing, removing impurities, and performing evaporating to remove solvents to obtain ibrutinib. The preparation method of the in