# US 2014/0155422 A1 · New Process for the Synthesis of Rifaximin and a New Pseudo-Crystalline Form of Rifaximin Obtained Thereby

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- Number: US 2014/0155422 A1
- Document ID: US20140155422A1
- Status: Published application
- Kind: A1
- Application number: 14/118,561
- Filed: 2012-05-21
- Published: 2014-06-05
- Earliest claimed: 2011-05-19
- Assignees: Friulchem SPA
- Applicants: Friulchem SPA
- Inventors: Disma Mazzola; Silvia Moiana; Germano Coppi
- Web page: https://patentgrep.com/patent/US20140155422A1

## CPC

- C07D 498/22: in which the condensed system contains four or more hetero rings
- A61P 31/04: Antibacterial agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Process for the preparation of rifaximin, pseudo-crystalline rifaximin and a new pseudo-crystalline form of rifaximin with fewer impurities obtained thereby.

## Claims

### Claim 1

A process for the preparation of rifaximin comprising the following steps:
a) Reacting under stirring a molar equivalent of rifamycin O with an excess of 2-amino-4-methylpyridine in a solvent comprising water, ethyl alcohol and acetone, at a temperature comprised between 15° C.-40° C. and for a period of time comprised between 20-35 hours;
b) Precipitating the solid by cooling the solution;
c) Filtering and washing the precipitated solid;
d) Suspending the precipitated solid in a mixture of ethyl alcohol and water comprising at least 95% ethyl alcohol, under heating at a temperature comprised between 35° C.-45° C. for 2.5-3.5 hours under stirring;
e) Cooling the suspension to a temperature of 10° C. in 60 minutes and keeping the solution at 10° C. for at least 30 additional minutes;
f) Filtering and washing the resulting solid;
g) Drying the solid.

### Claim 2 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein the 2-amino-4-methylpyridine is from 2 to 4 molar equivalents.

### Claim 3 (depends on 1)

The process for preparation of rifaximin according to claim 1 wherein the solvent comprises water, ethyl alcohol and acetone in a volumetric ratio comprised between 6:3:2 and 3:3:1.

### Claim 4 (depends on 1)

The process for preparation of rifaximin according to claim 1 wherein the solvent comprises water, ethyl alcohol and acetone in a volumetric ratio of 4:3:1.

### Claim 5 (depends on 1)

The process for preparation of rifaximin according to claim 1 wherein the reaction in step a) is performed at a pH comprised between 9.0 and 9.5.

### Claim 6 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein precipitating the solid in step b) is performed by cooling the solution to a temperature comprised between 0° C.-15° C. in a period of time comprised between 15-60 minutes.

### Claim 7 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein washing the precipitated solid in step c) comprises washing with a mixture of ethyl alcohol/water and final washing with water.

### Claim 8 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein in step d) the solid is suspended in ethyl alcohol and water under heating at a temperature comprised between 38° C.-42° C. for three hours.

### Claim 9 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein in step f) washing the resulting solid comprises washing with a mixture of ethyl alcohol and water.

### Claim 10 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein in step f) washing the resulting solid comprises washing with a mixture of ethyl alcohol and water in a volumetric ratio 1:2.

### Claim 11 (depends on 1)

The process for the preparation of rifaximin according to claim 1 wherein in step g) the solid is dried until the water content is comprised between 0.5% and 7%.

### Claim 12 (depends on 1)

A Rifaximin obtainable according to the process of claim 1.

### Claim 13 (depends on 12)

The Rifaximin according to claim 12 having the XRPD pattern as shown in FIG. 1.

### Claim 14 (depends on 12)

The Rifaximin according to claim 12 having an XRPD pattern with main peaks at about 5.9°, 7.3°, 7.9° and 8.4° 2theta.

### Claim 15 (depends on 12)

The Rifaximin according to claim 12 having a water content comprised between 0.5% and 7%.