Continuous preparation method of Zebrutinib

• Main Authors: ZHU WEIPING, CHEN YAN, XU YUFANG, QIAN XUHONG, YAN HAOHUI, WANG DERONG, LIU PEIWEN
• Format: Patent
• Language: Chinese; English
• Published: 25.06.2024
• Subjects: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; THEIR RELEVANT APPARATUS; TRANSPORTING

The invention provides a continuous preparation method of Zerbutinib, which specifically comprises the following steps: pumping a feed liquid A and a feed liquid B into a first microreactor, and carrying out addition reaction to obtain an addition product; pumping the feed liquid C and the feed liquid D into a second microreactor, and carrying out cyclization reaction to obtain a cyclized product; pumping the feed liquid E and hydrogen into a third fixed bed microreactor, and carrying out a reduction reaction to obtain a reduction product; pumping the feed liquid F and the feed liquid G into a fourth microreactor, and carrying out deprotection reaction to obtain a deprotection product; feeding liquid H containing methanesulfonic acid and water are pumped into a fifth microreactor and a sixth microreactor for hydrolysis reaction, and a hydrolysis product is obtained; and pumping the feed liquid I and the feed liquid J into a seventh microreactor, and carrying out substitution reaction to obtain a crude product