The present invention relates to a process for the preparation of delafloxacin meglumine
salt.

Background of the Invention Delafloxacin meglumine is chemically known as 1-deoxy-1-(methylamino)-D-glucitol, 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (salt), and is represented by Formula I.
OO
H3C
OH
i OH .IOH
NH
HO
HO' HO
F
HO
Formula I
Delafloxacin meglumine is a fluoroquinolone antibacterial indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria.
U.S. Patent No. 6,133,284 discloses delafloxacin and process for the preparation. PCT Publication No. WO 2006/015194 discloses process for the preparation of delafloxacin.
U.S. Patent No. 7,728,143 discloses crystalline forms of delafloxacin meglumine salt and delafloxacin meglumine trihydrate salt. U.S. Patent No. 7,728,143 discloses a processes for the preparation of delafloxacin meglumine salt either by treating a mixture of 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-1,4-dihydro-7-(3-hydroxyazetidin-1-yl)-4-oxo-3-
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quinolinecarboxylate and 1-deoxy-1-(methylamino)-D-glucitol with water and isopropanol or by dehydrating delafloxacin trihydrate salt.
There is still a need in the art to develop an improved process for the preparation of delafloxacin meglumine salt.
Summary of the Invention The present invention provides an improved, economical, and industrially advantageous process for the preparation for delafloxacin meglumine salt.
Brief Description of the Drawing Figure 1 depicts an X-Ray Powder Diffraction (XRPD) pattern of delafloxacin meglumine salt.
Detailed Description of the Invention The term “about,” as used herein, refers to any value which lies within the range defined by a number up to ±10% of the value.
The term “ambient temperature,” as used herein, refers to a temperature in the range of 25°C to 35°C.
A first aspect of the present invention relates to a process for the preparation of delafloxacin meglumine salt comprising
(a) treating 1-deoxy-1-(methylamino)-D-glucitol with a mixture of acetonitrile and water to obtain a suspension;
(b) adding delafloxacin base to the suspension;
(c) stirring the suspension obtained in step (b) to a temperature of 50°C to 60°C to obtain a solution;
(d) treating the solution obtained in step (c) with activated carbon to obtain a reaction mixture;
(e) filtering the reaction mixture obtained in step (d) to obtain a filtrate; and
(f) washing the filtrate with isopropyl alcohol to obtain delafloxacin meglumine salt.
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Delafloxacin base used for the preparation of delafloxacin meglumine salt may be prepared by any method provided in the art, for example, the methods as described in U.S. Patent No. 6,133,284 or PCT Publication No. WO 2006/015194.
In an embodiment, the treatment of 1-deoxy-1-(methylamino)-D-glucitol with a mixture of acetonitrile and water is carried out at ambient temperature for about 15 minutes to about 2 hours, for example, for about 15 minutes to about 30 minutes.
In another embodiment, the suspension of step (b) is stirred for about 15 minutes to about 2 hours, for example, for about 15 minutes to about 30 minutes.
In another embodiment, the reaction mixture of step (d) is heated at a temperature of about 40°C to about 55°C, for example, at about 45°C to about 50°C.
In another embodiment, the filtration of the suspension obtained in step (d) can be performed through a hyflo bed and/or a filter paper.
Accordingly, a suspension of 1-deoxy-1-(methylamino)-D-glucitol is obtained by treating 1-deoxy-1-(methylamino)-D-glucitol with a mixture of acetonitrile and water at an ambient temperature. This is followed by addition of delafloxacin base while heating at about 50°C to about 60°C to obtain a solution. Activated charcoal is added to the solution and the resultant reaction mixture is stirred for about 30 minutes to about one hour at about 40°C to about 55°C. The reaction mixture is filtered through a hyflo bed and/or a filter paper, washed with a mixture of acetonitrile and water. The filtrate is cooled to an ambient temperature while stirring for about 6 hours to about 8 hours. The solution was filtered, washed with isopropyl alcohol and dried under vacuum to obtain delafloxacin meglumine salt.
While the present invention has been described in terms of its specific aspects and embodiments, certain modifications and equivalents will be apparent to those skilled in the art, and are intended to be included within the scope of the present invention.
Method
XRPD of the sample was determined by using a PANalytical® instrument; Model X'pert PRO; Detector: X'celerator®.
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The following example is for illustrative purpose only and should not be construed as limiting the scope of the invention in any way.
EXAMPLE
Example 1: Preparation of delafloxacin meglumine salt
1-Deoxy-1-(methylamino)-D-glucitol (17.8 g) was added to a mixture of acetonitrile (136 mL) and water (68 mL) at an ambient temperature to obtain a suspension. Delafloxacin base (34 g) was added to the suspension and then heated to a temperature of 55°C to 60°C. The suspension was stirred for 30 minutes to obtain a solution. Activated charcoal (1.7 g) was added to the solution at 45°C to 50°C and stirred for 30 minutes to obtain a reaction mixture. The reaction mixture was filtered over hyflo bed and washed with acetonitrile (20 mL) and distilled water (10 mL) at 45°C to 50°C to obtain a filtrate. The filtrate was cooled to ambient temperature and stirred was 6 hours. The filtrate was filtered and washed with isopropyl alcohol to obtain a solid. The solid was sucked dried under vacuum at 55°C to 60°C to obtain tilted compound. Yield: 71.5% Purity: 99.87%

WE CLAIMS

A process for the preparation of delafloxacin meglumine salt comprising
(a) treating 1-deoxy-1-(methylamino)-D-glucitol with a mixture of acetonitrile and water to obtain a suspension;
(b) adding delafloxacin base to the suspension;
(c) stirring the suspension obtained in step (b) to a temperature of 50°C to 60°C to obtain a solution;
(d) treating the solution obtained in step (c) with activated carbon to obtain a reaction mixture;
(e) filtering the reaction mixture obtained in step (d) to obtain a filtrate; and
(f) washing the filtrate with isopropyl alcohol to obtain delafloxacin meglumine salt.

2. The process according to claim 1, wherein 1-deoxy-1-(methylamino)-D-glucitol is treated with a mixture of acetonitrile and water at an ambient temperature.
3. The process according to claim 1, wherein the suspension of step (b) is stirred for 15 minutes to 2 hours.
4. The process according to claim 1, wherein the reaction mixture of step (d) is heated at a temperature of 40ºC to 55ºC.
5. The process according to claim 1, wherein the filtration of the suspension of step (d) is performed through hyflo bed and/or filter paper.