The present invention relates to processes for the preparation of Type I, Type II and Type III crystals of Prulifloxacin.
Prulifloxacin is chemically 6-fluoro-1-methyl-7-{4-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]piperazin-1-yl}-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid of Formula I having the structure as depicted below:

Prulifloxacin has an excellent antibacterial activity and has been placed in the market as a synthetic antibacterial agent. US Patent No 5,086,049 provides a process for the preparation of prulifloxacin, wherein the final prulifloxacin is recrystallized from chloroform-methanol mixture.
IYAKUHIN KENKYU, Vol. 28(1), pp 1-11 (1997) provides processes for the preparation of Type I, Type II and Type III crystals of prulifloxacin by crystallization from acetonitrile. EP Publication No 1,626,051 mentions that Type III crystals have been placed in the market by considering the solubility, absorbability, therapeutic effect and the like of the respective crystal forms. EP '051 application further mentions that the conditions of crystallization from acetonitrile for preparing Type I, Type II and Type III crystals are not known through IYAKUHIN KENKYU, Vol. 28(1), pp 1-11 (1997).
EP '051 application provides processes for the preparation of Type I and Type II crystals from acetonitrile by the addition of respective seed crystals. However, EP '051 application does not disclose the details of the preparation of seed crystals. EP '051 application also provides a process for the preparation of acetonitrile solvate of prulifloxacin and the preparation of Type III crystals by desolvation of said solvate. EP '051 application further quotes that acetonitrile solvate is an important intermediate for producing Type III crystals and Type III crystals are not directly obtained by recrystallization from acetonitrile. The process provided in EP '051 application for the

preparation of acetonitrile solvate is observed to be complicated and it requires monitoring of supersaturation concentration at specific ranges.
The present inventors have developed simple methods for the preparation of Type I, Type II and Type III crystals from acetonitrile. The present process does not involve the addition of seed crystals at any stage. Further, the present inventors have surprisingly found that Type III crystals can be obtained directly by crystallization from acetonitrile without involving the preparation and desolvation of acetonitrile solvate. By employing the present invention, prulifloxacin present in any solid form can be converted into Type I, Type II or Type III crystal form. Thus the present invention provides simple, cost effective and industrially preferable processes for the preparation of Type I, Type II and Type III crystals of prulifloxacin.
A first aspect of the present invention provides a process for the preparation of Type I crystals of prulifloxacin, wherein said process comprises,
a) dissolving prulifloxacin in acetonitrile by heating to a temperature of about 75°C or
more,
b) cooling the solution obtained in step a) to a temperature of about 25°C to about 35°C
in about 2 hours or more,
c) isolating Type I crystals of prulifloxacin from the reaction mixture thereof.
Prulifloxacin present in any crystalline form can be used as a starting material. The prulifloxacin is dissolved in acetonitrile by heating to a temperature of about 75°C or more. The solution so obtained is cooled to a temperature of about 25°C to about 35°C in about 2 hours or more. After the formation of crystals, the reaction mixture is optionally further cooled to about 0°C to about 10°C accompanied by stirring. The crystals are then dried to obtain Type I crystals of prulifloxacin.
A second aspect of the present invention provides a process for the preparation of Type II crystals of prulifloxacin, wherein said process comprises,
a) dissolving prulifloxacin in acetonitrile by heating to a temperature of about 75°C or
more,
b) cooling the solution obtained in step a) to a temperature of about 0°C to about 10°C
in about 1 hour or less,
c) isolating Type II crystals of prulifloxacin from the reaction mixture thereof.

Prulifloxacin present in any crystalline form can be used as a starting material. The prulifloxacin is dissolved in acetonitrile by heating to a temperature of about 75°C or more. The solution so obtained is cooled to a temperature of about 0°C to about 10°C in about 1 hour or less. The reaction mixture is stirred at the same temperature to effect maximum crystallization. The crystals are then dried to obtain Type II crystals of prulifloxacin.
A third aspect of the present invention provides a process for the preparation of Type III crystals of prulifloxacin, wherein said process comprises,
a) dissolving prulifloxacin in acetonitrile by heating to a temperature of about 75°C or
more,
b) cooling the solution obtained in step a) to a temperature of about 25°C to about 35°C
in about 1 hour or less,
c) isolating Type III crystals of prulifloxacin from the reaction mixture thereof.
Prulifloxacin present in any crystalline form can be used as a starting material. The prulifloxacin is dissolved in acetonitrile by heating to a temperature of about 75°C or more. The solution so obtained is cooled to a temperature of about 25°C to about 35°C in about 1 hour or less. After the formation of crystals, the reaction mixture is optionally further cooled to about 0°C to about 10°C accompanied by stirring. The crystals are then dried to obtain Type III crystals of prulifloxacin.
While the present invention has been described in terms of its specific 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.
EXAMPLE 1
PROCESS FOR THE PREPARATION OF TYPE I CRYSTALS OF PRULIFLOXACIN:
Prulifloxacin (100 g) was dissolved in acetonitrile (5.5 L) at reflux temperature. The undissolved materials were filtered out. The filtrate obtained was cooled slowly for 8 h to 28°C.The reaction mixture was then cooled to 5°C and stirred for 3 h. The solid obtained was dried at 60°C for 24 h to get the title compound.

EXAMPLE 2 PROCESS FOR THE PREPARATION OF TYPE II CRYSTALS OF PRULIFLOXACIN:
Prulifloxacin (100 g) was dissolved in acetonitrile (5.5 L) at reflux temperature. The undissolved materials were filtered out. The filtrate obtained was cooled rapidly to 5° to 7°C in 10 minutes and stirred for 3 h. The solid obtained was dried at 55°C for 24 h to obtain the title compound.
EXAMPLE 3
PROCESS FOR THE PREPARATION OF TYPE III CRYSTALS OF PRULIFLOXACIN:
Prulifloxacin (100 g) was dissolved in acetonitrile (5.5 L) at reflux temperature. The undissolved materials were filtered out. The filtrate obtained was cooled to 28°C in 30 minutes, and subsequently to 5°C followed by stirring for 3h. The solid obtained was dried at 60°C for 24 h to obtain the title compound.

WE CLAIM:
1. A process for the preparation of Type I crystals of prulifloxacin, wherein said process
comprises,
a) dissolving prulifloxacin in acetonitrile by heating to a temperature of about 75°C or
more,
b) cooling the solution obtained in step a) to a temperature of about 25°C to about 35°C
in about 2 hours or more, and
c) isolating Type I crystals of prulifloxacin from the reaction mixture thereof.

2. A process according to claim 1, wherein step b) further comprises cooling the
reaction mixture to about 0°C to about 10°C.
3. A process according to claim 2, wherein step b) further comprises stirring.
4. A process for the preparation of Type II crystals of prulifloxacin, wherein said process
comprises,

a) dissolving prulifloxacin in acetonitrile by heating to a temperature of about 75°C or
more,
b) cooling the solution obtained in step a) to a temperature of about 0°C to about 10°C
in about 1 hour or less,
c) isolating Type II crystals of prulifloxacin from the reaction mixture thereof.

5. A process according to claim 4, wherein step b) further comprises stirring.
6. A process for the preparation of Type III crystals of prulifloxacin, wherein said
process comprises,

a) dissolving prulifloxacin in acetonitrile by heating to a temperature of about 75°C or
more,
b) cooling the solution obtained in step a) to a temperature of about 25°C to about 35°C
in about 1 hour or less,
c) isolating Type I crystals of prulifloxacin from the reaction mixture thereof.

7. A process according to claim 6, wherein step b) further comprises cooling the
reaction mixture to about 0°C to about 10°C.
8. A process according to claim 7, wherein step b) further comprises stirring.