Process for the preparation of biphosphonic acids

Abstract

An improved process for bisphosphonylation of acids, substituted acids to obtain compounds with the formula

Description

Claims

1. An improved process for the preparation of bisphosphonic derivatives of Formula (I),

2. The process according to claim 1, wherein the halophosphorus compound is selected from phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, phosphorus tribromide, phosphorus oxybromide, phosphorus pentabromide or mixtures thereof.

3. The process according to claim 1, wherein the solvent is selected from phenol or substituted phenols.

4. The process according to claim 3, wherein phenol or substituted phenols is selected from o-cresol, m-cresol, p-cresol, o-fluorophenol, m-fluorophenol, p-fluorophenol, o-chlorophenol, m-chlorophenol, p-chlorophenol, o-bromophenol, m-bromophenol, p-bromophenol, o-iodophenol, m-iodophenol, p-iodophenol, o-aminophenol, m-aminophenol, p-aminophenol, o-nitrophenol, m-nitrophenol, p-nitrophenol, 2,4-dintrophenol, 2,4,6-trinitrophenol 2,6-ditertiary butyl-4-methyl phenol or mixtures thereof, more preferably phenol.

5. The process according to claim 1, wherein the carboxylic acid is selected from the group consisting of 4-aminobutyric acid, 3-aminopropionic acid, 3-pyridyl acetic acid, 1-imidazoylacetic acid, N-(n-pentyl)-N-methyl-3-aminopropionic acid, 2-(imidazo[1,2-a]pyridin-2-yl)ethanoic acid, and 6-aminohexanoic acid, 3-(dimethylamino)propionic acid.

6. The process according to claim 1, wherein the carboxylic acid is 4-aminobutyric acid.

7. The process according to claim 1, wherein the carboxylic acid is 3-pyridylacetic acid.

8. The process according to claim 1, wherein the carboxylic acid is N-(n-pentyl)-N-methyl-3-aminopropionic acid.