Process for making 1-hydroxyalkylidene-1,1-biphosphonic acids
AssigneeSynthon BV
InventorJiri Bartl
Life of this patent
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Abstract
Synthesis of biphosphonate compounds can be advantageously carried out in a solvent/diluent comprising a compound of formula (3) wherein R is hydrogen or a C1-C6 alkyl group; each of R1 is a C1-C6 alkyl group or both R1 groups are linked to form a C1-C3 alkylene group; and R2 is hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, or is linked together with R to form a C3-C7 carbon ring.
Claims13
A process of making a biphosphonate, which comprises:
- reacting in a solvent/diluent a carboxylic acid compound of formula (2) or a salt thereof
- Z—COOH (2),
- wherein Z represents a C1-C6 alkyl group optionally substituted by an amino group, one or two C1-C6 alkylamino group(s), or a nitrogen-containing heterocyclic group, with a phosphonation agent to form cyclic pyrophosphonate intermediates, wherein said solvent/diluent comprises at least one compound of formula (3)
- wherein R is hydrogen or a C1-C6 alkyl group;
- each of R1 is a C1-C6 alkyl group or both R1 groups are linked to form a C1-C3 alkylene group;
- and R2 is hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, or is linked together with R to form a C3-C7 carbon ring;
- and
- hydrolyzing said cyclic pyrophosphonate intermediates to form a compound of formula (1) or a salt or hydrate thereof
- wherein Z is as defined above.
In a process of making biphosphonate compounds by reacting an acid or ester with a phosphonation agent, the improvement for which comprises carrying out said reaction in a solvent/diluent that comprises a compound of formula (3)
- wherein R is hydrogen or a C1-C6 alkyl group;
- each of R1 is a C1-C6 alkyl group or both R1 groups are linked to form a C1-C3 alkylene group;
- and R2 is hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, or is linked together with R to form a C3-C7 carbon ring.
Dependencies are inferred from the claim text.