Abstract

Ibandronate and Alendronate/Alendronic acid were prepared by the reaction of the corresponding amino acids (N-methyl-Npentylalanine and γ-aminobutyric acid) with 3.2 equivalents of phosphorus trichloride, in the absence of any phosphorous acid, in methanesulfonic acid at 75 °C for 12 h followed by hydrolysis, pH adjustment and purification. The first intermediate of the reaction sequence is the corresponding chloride (>N(CH2)nC(O)Cl) or mixed ester (>N(CH2)nC(O)OS(O)2Me).

Keywords: Ibandronate, Alendronate, Synthesis, Optimization, Intermediate.