Synthetic study of vonoprazan fumarate / 国际药学研究杂志
Journal of International Pharmaceutical Research
; (6): 890-893, 2017.
Article
in Zh
| WPRIM
| ID: wpr-693331
Responsible library:
WPRO
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.
Full text:
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Database:
WPRIM
Language:
Zh
Journal:
Journal of International Pharmaceutical Research
Year:
2017
Document type:
Article