Preparation and use of .alpha.-Keto Bisphosphonates
US6147245A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Jul 13, 1999 |
| Grant date | Nov 14, 2000 |
| Priority date | — |
| Expiry date | Jul 13, 2019 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07F9/4065
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
A unique method for the synthesis of substantially pure .alpha.-keto bisphosphonate esters and the usage of these esters in reactions with C, N, O, or P nucleophiles for synthesis of .alpha.-functionalized bisphosphonates. The method starts with a reaction mixture formed of an .alpha.-diazo methanediphosphonate ester, including tert-butylchlorite, a polar aprotic organic solvent, and an effective amount of water. After synthesis is complete, a water trapping reagent may be added to remove any excess water. The present invention provides a versatile pathway to new .alpha.-substituted bisphosphonate derivatives and could be readily adapted to combinatorial drug discovery synthetic strategies. The .alpha.-keto bisphosphonate esters can be converted to the corresponding acids by acid hydrolysis or mild silyldealkylation.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.