Synthetic study of vonoprazan fumarate

VernacularTitle:富马酸沃诺拉赞的合成研究
Author: Jiu-An LV ¹ ; Kai ZHANG ; Ke-Jun ZHANG ; Long-Tao FAN ; Xiao-Ming PENG ; Jian-Ping CHAO
Author Information

1. 北京红惠新医药科技有限公司
Keywords: protonpump inhibitor; vonoprazan fumarate; synthesis study
From: Journal of International Pharmaceutical Research 2017;44(9):890-893
CountryChina
Language:Chinese
Abstract: Objective To develop a practical synthetic process of vonoprazan fumarate with high-yield and lower impurities to meet the quality requirements. Methods By using 5-(2-fluorophenyl)pyrrole-3-carboxaldehyde as the starting material,the qualified vonoprazan fumarate was synthesized via the following steps:①N-sulfonylation and the chloride impurity was removed by recrystalli-zation from MeOH;②the aldehyde was converted to amine by reductive amination,followed by forming the vonoprazan chloride to re-move the dimethylamino impurity;③vonoprazan free base was obtained by neutralization and then converted to fumarate at room tem-perature and finally recrystallized from MeOH/H2O(1:1). Results An impurity controllable synthetic process was developed with a 4％total yield improving. The final product was confirmed by ESI-MS and 1H NMR. Conclusion The synthetic process with single im-purity less than 0.1％and purity above 99.5％was obtained and suitable for scale production of vonoprazan fumarate.