IBANDRONATE
IBANDRONATE Basic information
- Product Name:
- IBANDRONATE
- Synonyms:
-
- IBANDRONATE
- IBANDRONATE NA
- MF:
- C9H23NO7P2
- MW:
- 319.23
- Mol File:
- Mol File
IBANDRONATE Usage And Synthesis
Description
This bisphosphonate, a calcium metabolic inhibitor and osteogenesis inhibitor, was developed and launched by Boehringer Mannheim (now Roches) for the treatment of tumor-induced hypercalcemia (TIH) and is available in both injectable and oral formulations. In In collaboration with GlaxoSmithKline, the ibandronic acid was also developed in both iv and oral formulations for the treatment and prevention of postmenopausal osteoporosis.
Synthesis
The synthesis of ibandronate sodium (XIII) is shown in the scheme. However some reaction details are not available in the literature. N -pentylamine (110) was reacted with benzaldehyde to give oily Schiff base 111 in 94% yield. Hydrogenation with palladium/charcoal gave N-benzyl-Npentylamine as oil in 74% yield. The secondary amine was reductively alkylated with formaldehyde and formic acid to give the tertiary amine 112 in 95% yield. Hydrogenolytic cleavage of the benzyl group of 112 with palladium/charcoal gave secondary amine 113, which was reacted with methyl acrylate (114) in toluene to give compound 115 in 93% yield. Methyl ester 115 was then saponified with 1N NaOH to give carboxylic acid. The acid was then heated to 80oC with phosphorous acid. The melt was mixed with phosphorus oxychloride at the same temperature for 16 hours. Water was then added and the reaction mixture was stirred at 100°C for 24 hours to give free diphosphonic acid. The free diphosphonic acid was finally treated with sodium hydroxide to give ibandronate sodium (XIII).