Stable crystalline form of bifeprunox mesylate (7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate)

1. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2 θ at approximately 7.0, 9.3, 10.0, 12.5, 15.4, 16.7, 17.2, 17.4, 17.7, 18.7, 21.3, 22.2, 25.2, 27.2, 28.3, 28.8 and 30.1.

2. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, having a melting point at approximately 277° C.

3. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting a DSC trace as shown in FIG. 2 .

4. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting an attenuated total reflectance infrared spectrum having characteristic absorption bands expressed in reciprocal centimeters at approximately 1764, 1217, 795, 746 and 694.

5. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, according to claim 4 , exhibiting an attenuated total reflectance infrared spectrum having characteristic absorption bands expressed in reciprocal centimeters at approximately 1764, 1636, 1284, 1217, 809, 795, 746, 694, 663 and 509.

6. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting an infrared spectrum as shown in FIG. 3 .

7. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting 13 C solid state NMR chemical shifts expressed relative to glycine (δ c =176.03 for the C═O resonance) at approximately 40.4, 48.7, 56.5, 106.8 and 137.7 ppm.

8. A crystalline polymorph of 7-[4-([1,1′-biphenyll]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate according to claim 7 , exhibiting 13 C solid state NMR chemical shifts expressed relative to glycine (δ c =176.03 for the C═O resonance) at approximately 40.4, 48.7, 50.3, 56.5, 106.8, 110.7, 124.9, 126.9, 127.8, 129.2, 130.8, 134.2, 137.7, 141.6, and 153.8 ppm.

9. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting a 13 C solid state NMR chemical as shown in FIG. 4 .

10. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate exhibiting a single crystal X-ray crystallographic analysis at 150 K with (a) crystal parameters that are approximately equal to the following:

Cell dimensions

a = 9.283 Å

b = 10.737 Å

c = 12.690 Å

α = 98.553°

β = 93.749°

γ = 116.097°

Crystal system

triclinic

Space group

P-1

Molecules/unit cell

2

Density (g/cm 3 )

1.481.

and (b) atomic positions of all atoms relative to the origin of the unit cell as recited in Table 5.

11. A crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting a single X-ray diffraction as shown in FIG. 5 .

12. A composition comprising 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, wherein at least about 50 weight % of the 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate is in the crystalline polymorphic form α.

13. The composition according to claim 12 , wherein at least about 60 weight % of the 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1 -piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate is in the crystalline polymorphic form α.

14. The composition according to claim 13 , wherein at least about 80 weight % of the 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1 -piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate is in the crystalline polymorphic form α.

15. The composition according to claim 14 , wherein at least about 90 weight % of the 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate is in the crystalline polymorphic form α.

16. The composition according to claim 15 , characterized in that at least 95 weight % of the 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate is in the crystalline polymorphic form α.

17. A process for the preparation of crystalline polymorphic form αof 7-[4-([1,1′-biphenyl]-3-yimethyl)-1-piperazinyl]-2(3H )-benzoxazolone monomethanesulfonate comprising crystallizing 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate from a solution thereof in an organic solvent or a mixture of an organic solvent with water.

18. A process for the preparation of crystalline polymorphic form α of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, comprising recrystallizing crystalline polymorphic formγ or δ of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate or a mixture of crystalline polymorphic forms γ and δ from a solution thereof in an organic solvent or a mixture of an organic solvent with water.

19. The process according to claim 17 , wherein said organic solvent is chosen from 2-propanol and acetonitrile.

20. The process according to claim 18 , wherein said organic solvent is chosen from 2-propanol and acetonitrile.