# US 7,411,087 B2 · Process for preparation of bisphosphonic acid compounds

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- Number: US 7,411,087 B2
- Document ID: US7411087B2
- Status: Granted
- Kind: B2
- Application number: 10/569,308
- Filed: 2004-08-10
- Published: 2006-12-28
- Granted: 2008-08-12
- Earliest claimed: 2003-08-21
- Assignees: Sun Pharmaceutical Industries Limited
- Inventors: Vijaykumar Muljibhai Patel; Trinadha Rao Chitturi; Rajamannar Thennati
- Web page: https://patentgrep.com/patent/US7411087B2

## CPC

- C07F 9/3873: {containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)}
- C07F 9/58: Pyridine rings
- C07F 9/6506: having the nitrogen atoms in positions 1 and 3
- C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention provides a novel process for preparation of bisphosphonic acids or salts thereof, e.g. alendronic acid, by reacting a carboxylic acid, phosphorous acid and a halophosphorous compound in a water miscible neutral solvent.

## Claims

### Claim 1

A process for preparation of bisphosphonic acid, a compound of formula 1 or a salt thereof,
comprising reacting a carboxylic acid compound of formula 2 or a salt thereof
wherein,
A is a straight chain alkyl, a branched alkyl or a cyclic alkyl chain with up to 10 carbon atoms, which can optionally contain hetero atoms in between and,
B is alkyl, aralkyl, aromatic or heteroaromatic group, which can be optionally substituted;
or
wherein, R1 and R2 may be selected from hydrogen or straight chain, branched or cyclic lower alkyl,
with phosphorous acid and a phosphorous chloride selected from PCl3, PCl5 and POCl3, in sulfolane.

### Claim 2 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 4-aminobutyric acid and the bisphosphonic acid is alendronic acid.

### Claim 3 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 3-aminopropionic acid and the bisphosphonic acid is pamidronic acid.

### Claim 4 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 3-pyridylacetic acid and the bisphosphonic acid is risedronic acid.

### Claim 5 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 1-imidazolylacetic acid and the bisphosphonic acid is zoledronic acid.

### Claim 6 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is N-(n-pentyl)-N-methyl-3-aminopropionic acid and the bisphosphonic acid is ibandronic acid.

### Claim 7 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 2-(imidazo[1,2-a]pyridin-2-yl)ethanoic acid and the bisphosphonic acid is minodronic acid.

### Claim 8 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 6-aminohexanoic acid and the bisphosphonic acid is neridronic acid.

### Claim 9 (depends on 1)

The process as claimed in claim 1, wherein the carboxylic acid is 3-(dimethylamino)propionic acid and the bisphosphonic acid is olpadronic acid.

### Claim 10 (depends on 2)

The process as claimed in claim 2, wherein the yield of alendronic acid is 69% of theoretical yield and the purity of the alendronic acid is at least 99%.

### Claim 11 (depends on 3)

The process as claimed in claim 3, wherein the yield of pamidronic acid is 76% of theoretical yield and the purity of the pamidronic acid is at least 99%.

### Claim 12 (depends on 4)

The process as claimed in claim 4, wherein the yield of risedronic acid is 70% of theoretical yield and the purity of the risedronic acid is at least 99%.

### Claim 13 (depends on 5)

The process as claimed in claim 5, wherein the yield of zoledronic acid is at least about 70% of theoretical yield.

### Claim 14 (depends on 5)

The process as claimed in claim 5, wherein the purity of the zoledronic acid is at least 99.5%.