# US 8,772,503 B2 · Processes for the preparation of deferasirox, and deferasirox polymorphs

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,772,503 B2
- Document ID: US8772503B2
- Status: Granted
- Kind: B2
- Application number: 13/514,155
- Filed: 2010-01-28
- Published: 2012-09-27
- Granted: 2014-07-08
- Earliest claimed: 2009-12-07
- Assignees: Mapi Pharma Ltd.
- Applicants: Michael Mizhiritskii; Ehud Marom; Shai Rubnov
- Inventors: Michael Mizhiritskii; Ehud Marom; Shai Rubnov
- Web page: https://patentgrep.com/patent/US8772503B2

## CPC

- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- A61P 3/12: for electrolyte homeostasis
- A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04)
- A61P 39/04: Chelating agents
- C07D 291/06: Six-membered rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to processes for the preparation of deferasirox, an oral iron chelator developed to treat iron overload due to e.g. multiple blood transfusions. The present invention further provides novel deferasirox pseudopolymorphs and a novel amorphous form of deferasirox, processes for their preparation, as well as pharmaceutical compositions comprising same, and use thereof in treating iron overload.

## Claims

### Claim 1

A process for the preparation of deferasirox, comprising the steps of:
a) converting salicylic acid to its acyl chloride:
b) reacting salicyl chloride with an amidating reagent so as to produce a deferasirox intermediate of formula:
and
c) reacting intermediate with 4-hydrazinobenzoic acid to form deferasirox:

### Claim 2 (depends on 1)

The process according to claim 1, wherein the amidating reagent in step (b) is selected from the group consisting of disilazanes of general formula (R1R2R3Si)2NH and cyclosilazanes of general formula (R1R2SiNH)n, wherein n is 3 or 4 and R1, R2 and R3 are each independently alkyl or aryl.

### Claim 3 (depends on 1)

The process according to claim 1, wherein in step (b) the reaction between salicyl chloride and the amidating reagent is conducted in the presence of catalyst, wherein the catalyst is selected from the group consisting of tertiary amine selected from the group consisting of triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, lutidine, DBU, DBN, DABCO and picoline.

### Claim 4 (depends on 1)

The process according to claim 1, wherein step (a) and step (b) are combined as a one-pot synthesis.

### Claim 5 (depends on 1)

The process according to claim 1, wherein step (c) is performed in a solvent in the presence of acid, wherein the solvent is selected from the group consisting of alcohols, ethers, DMF, NMP, DMSO, water and mixtures thereof; and wherein the acid is an inorganic acid selected from the group consisting of hydrochloric acid, hydrobromic acid, phosphoric acid and sulfuric acid; or an organic acid selected from the group consisting of formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid and propionic acid.

### Claim 6 (depends on 1)

The process according to claim 1, wherein step (b) is conducted in a solvent selected from the group consisting of hydrocarbons and halogenated hydrocarbons, aromatic hydrocarbons and halogenated aromatic hydrocarbons, esters, ethers, carboxylic acid amides, acetonitrile, and mixtures of these solvents.

### Claim 7 (depends on 6)

The process according to claim 6, wherein the solvent is DMF or toluene.

### Claim 8 (depends on 2)

The process according to claim 2, wherein the amidating reagent is hexamethyldisilizane.

### Claim 9 (depends on 3)

The process according to claim 3, wherein the catalyst in step (b) is pyridine or DMF.

### Claim 10 (depends on 4)

The process according to claim 4, wherein step (a) and (b) are conducted in toluene.