Efficient Synthesis of Ibandronate in the Presence of an Ionic Liquid

Author(s): David Illes Nagy, Alajos Grun, Oliver Pavela, Sandor Garadnay, Istvan Greiner, Gyorgy Keglevich*

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 7 , 2018

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Graphical Abstract:


Background: Ibandronate is a prominent representative of α-hydroxymethylenebisphosphonic acid (dronic acid) derivatives applied in the treatment of bone diseases.

Methods: Ibandronate was synthesized from N-methyl-N-pentyl-β-alanine using phosphorus trichloride and phosphorous acid in different ratios, applying sulfolane as the solvent (1.), or under solvent-free conditions (2.), or in ionic liquids as additives (3.).

Results: In the first two cases (1. and 2.), using phosphorus trichloride and phosphorous acid in molar ratios of 2:4 and 3:4, pure ibandronate was obtained in yields of 72-83%. In the presence of 10% of [bmim][BF4] as an additive (3.), a better yield of 82/90% was obtained applying ratios of 2:2 and 3:2 of the P-reagents assuming less of the phosphorous acid.

Conclusion: The new methods developed mean record outcomes in respect of the valuable drug, ibandronate.

Keywords: Ibandronate, N-methyl-N-pentyl-β-alanine, P-reagents, sulfolane, ionic liquid additive, osteoporosis.

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Article Details

Year: 2018
Page: [713 - 720]
Pages: 8
DOI: 10.2174/1570180814666171027160324

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