Efficient synthesis of ibandronate in the presence of an ionic liquid

Dávid Illés Nagy, A. Grün, Olivér Pavela, Sándor Garadnay, István Greiner, G. Keglevich

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalLetters in Drug Design and Discovery
Volume15
Issue number7
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Ionic Liquids
Acids
Bone Diseases
Alanine
ibandronic acid
Pharmaceutical Preparations
phosphonic acid
phosphorus chloride

Keywords

  • Ibandronate
  • Ionic liquid additive
  • N-methyl-n-pentyl-β-alanine
  • Osteoporosis
  • P-reagents
  • Sulfolane

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Efficient synthesis of ibandronate in the presence of an ionic liquid. / Nagy, Dávid Illés; Grün, A.; Pavela, Olivér; Garadnay, Sándor; Greiner, István; Keglevich, G.

In: Letters in Drug Design and Discovery, Vol. 15, No. 7, 01.01.2018, p. 713-720.

Research output: Contribution to journalArticle

Nagy, Dávid Illés ; Grün, A. ; Pavela, Olivér ; Garadnay, Sándor ; Greiner, István ; Keglevich, G. / Efficient synthesis of ibandronate in the presence of an ionic liquid. In: Letters in Drug Design and Discovery. 2018 ; Vol. 15, No. 7. pp. 713-720.
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AB - 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.

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