A Study on the Synthesis of Risedronic Acid: The Role of an Ionic liquid Additive

被引：6
作者：
Nagy, David Illes [1 ]
Grun, Alajos [1 ]
Sinkovicz, Julia [1 ]
Garadnay, Sandor [2 ]
Greiner, Istvan [2 ]
Keglevich, Gyorgy [1 ]
机构：
[1] Budapest Univ Technol & Econ, Dept Organ Chem & Technol, H-1521 Budapest, Hungary
[2] Gedeon Richter Plc, H-1475 Budapest, Hungary
来源：
LETTERS IN DRUG DESIGN & DISCOVERY | 2019年 / 16卷 / 03期
关键词：
Risedronic acid; 3-pyridylacetic acid; P-reagents; sulfolane; ionic liquid additive; optimization; HETEROCYCLIC DRONIC ACIDS; EFFICIENT SYNTHESIS; ZOLEDRONIC ACID; BISPHOSPHONATES; NITROGEN;
D O I：
10.2174/1570180815666180626122630
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Background: The synthesis of high value risedronic acid is not fully resolved, as, for the time being, the best method based on the preparation from 3-pyridylcarboxylic acid by reaction with phosphorus trichloride in methanesulfonic acid gives risedronic acid in a good yield, but in an unpure form. Methods: Alternative protocols realizing the synthesis in sulfolane as the solvent and/or in the presence of suitable IL additive were developed to obtain the target dronic acid in a pure form. Results & Conclusion: Using phosphorus trichloride and phosphorous acid in two equivalents quantities together with 0.6 equivalents of [bmim][BF4] without any solvent, the method afforded the target dronic acid in a yield of 66% in a pure form.
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收藏
页码：238 / 244
页数：7
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