DESC:FIELD OF THE INVENTION
The present invention relates to solvates of Lumacaftor including Lumacaftor dichloromethane solvate, Lumacaftor 1,4-dioxane solvate and Lumacaftor 1,4-dioxane-water solvate. The present invention also relates to the process for preparation of these solvates.

BACKGROUND OF THE INVENTION
The present invention is related to lumacaftor which is a drug for the treatment of cystic fibrosis. The drug is designed to be effective in patients that have the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein that causes the disease.

(I)
Lumacaftor (I) chemically known as 3-[6-({[1-(2,2-difluoro-1,3-benzodioxol-5-yl) cyclopropyl]carbonyl}amino)-3-methylpyridin-2-yl]benzoic acid is disclosed in the PCT application WO 2007/056341. The patent US 8,507,534 discloses crystalline form I of Lumacaftor.

US 20150080431 discloses various solvates of Lumacaftor as methanol solvate form A, ethanol solvate form A, acetone solvate form A, 2-propanol solvate form A, acetonitrile solvate form A, tetrahydrofuran solvate form A, methyl acetate solvate form A, 2-butanone solvate form A, ethyl formate solvate form A etc.

SUMMARY OF THE INVENTION
The present invention relates to Lumacaftor dichloromethane solvate, Lumacaftor 1,4-dioxane solvate and Lumacaftor 1,4-dioxane-water.

The present invention further provides process for the preparation of Lumacaftor dichloromethane solvate, Lumacaftor 1,4-dioxane solvate and Lumacaftor 1,4-dioxane-water.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1 - XRPD diffractogram for Lumacaftor dichloromethane solvate
Figure 2 - DSC for Lumacaftor dichloromethane solvate
Figure 3 - XRPD diffractogram for Lumacaftor 1,4-dioxane solvate
Figure 4 - DSC for Lumacaftor 1,4-dioxane solvate
Figure 5 - XRPD diffractogram for Lumacaftor 1,4-dioxane-water solvate
Figure 6 - DSC for Lumacaftor 1,4-dioxane-water solvate

DETAILED DESCRIPTION OF THE INVENTION
In one embodiment there is provided Lumacaftor dichloromethane solvate.
Lumacaftor dichloromethane solvate of the present invention can be characterized by X-ray crystallography and differential scanning calorimetry (DSC).
In another embodiment there is provided Lumacaftor 1,4 dioxane solvate.
Lumacaftor 1,4 dioxane solvate of the present invention can be characterized by X-ray crystallography and differential scanning calorimetry (DSC).
In another embodiment there is provided Lumacaftor 1,4-dioxane-water solvate.
Lumacaftor 1,4-dioxane-water solvate of the present invention can be characterized by X-ray crystallography and differential scanning calorimetry (DSC).
In another embodiment there is provided Lumacaftor dichloromethane solvate wherein said Lumacaftor dichloromethane solvate is characterized by a powder X-ray diffraction pattern comprising peaks at 6.21, 8.84, 10.87, 12.21, 16.52, 17.95, 20.47, 21.54 degree 2-theta + 0.2 degree 2-theta.
The XRPD of Lumacaftor dichloromethane solvate is as shown in figure 1.
In yet another embodiment there is provided Lumacaftor 1,4 dioxane solvate wherein said Lumacaftor 1,4 dioxane solvate is characterized by a powder X-ray diffraction pattern comprising peaks at 6.49, 9.27, 10.42 degree 2-theta + 0.2 degree 2-theta.
The XRPD of Lumacaftor 1,4 dioxane solvate is as shown in figure 3.
In another embodiment there is provided Lumacaftor 1,4 dioxane-water solvate wherein said Lumacaftor 1,4 dioxane-water solvate is characterized by a powder X-ray diffraction pattern comprising peaks at 8.77, 9.23, 10.67 degree 2-theta + 0.2 degree 2-theta.
The XRPD of Lumacaftor 1,4 dioxane solvate is as shown in figure 5.

In another embodiment there is provided process for the preparation of Lumacaftor dichloromethane solvate.
Lumacaftor dichloromethane solvate is prepared by dissolving Lumacaftor in dichloromethane, heating the solution followed by cooling and isolation. The quantity of dichloromethane used is around 20 ml to 100 ml for 1 gm of Lumacaftor.
In further embodiment there is provided process for the preparation of Lumacaftor 1,4 dioxane solvate.
Lumacaftor 1,4 dioxane solvate is prepared by dissolving Lumacaftor in 1,4 dioxane, heating the solution followed by cooling and isolation. The quantity of 1,4 dioxane used is around 2 ml to 50 ml for 1 gm of Lumacaftor.
In yet another embodiment there is provided process for the preparation of Lumacaftor 1,4 dioxane-water solvate.
Lumacaftor 1,4 dioxane solvate is prepared by dissolving Lumacaftor in 1,4 dioxane-water mixture, heating the solution followed by cooling and isolation. The ratio of 1,4 dioxane to water used is around 1: 0.1 to 20: 15. The quantity of the solvent mixture used is 2 ml to 50 ml for 1 gm of Lumacaftor.

Experimental:
The X-ray powder diffraction spectrum (XRPD) was recorded at room temperature using PANalytical X’Pert PRO diffractogram with Cu Ka radiation (? = 1.54060 Å), running at 45 kV and 40 mA.
The present invention is described in the following examples, however it should be noted that the scope of present invention is not limited by the examples.
Example 1: Preparation of Lumacaftor dichlormethane solvate.
Lumacaftor (5gm) was added to dichloromethane (250 ml). The mixture was heated to get a clear solution. The reaction mass was stirred, cooled and chilled. The solid was filtered and dried under reduced pressure.
Yield: 2.2 gm.
Example 2: Preparation of Lumacaftor 1,4 dioxane solvate.
Lumacaftor (10 gm) was added to 1,4 dioxane (60 ml). The mixture was heated to get a clear solution. The reaction mass was stirred, cooled and chilled. The solid was filtered and dried under reduced pressure.
Yield: 6.2 gm.
Example 1: Preparation of Lumacaftor 1,4 dioxane-water solvate.
Lumacaftor (10 gm) was added to 1,4 dioxane: water mixture (8: 2) (70 ml). The mixture was heated to get a clear solution. The reaction mass was stirred, cooled and chilled. The solid was filtered and dried under reduced pressure.
Yield: 7.5 gm.
,CLAIMS:1) Lumacaftor dichloromethane solvate.
2) Process for the preparation of lumacaftor dichloromethane solvate comprising dissolving lumacaftor in dichloromethane, heating the solution followed by cooling.
3) Lumacaftor dichloromethane solvate as described in claim 1 having XRD shown in figure 1.
4) Lumacaftor 1,4-dioxane solvate.
5) Process for the preparation of lumacaftor 1,4 dioxane solvate comprising dissolving lumacaftor in 1,4 dioxane, heating the solution followed by cooling.
6) Lumacaftor 1,4-dioxane solvate as described in claim 1 having XRD shown in figure 3.
7) Lumacaftor 1,4-dioxane-water solvate.
8) Process for the preparation of lumacaftor 1,4 dioxane-water solvate comprising dissolving lumacaftor in 1,4 dioxane and water mixture, heating the solution followed by cooling.
9) Lumacaftor 1,4-dioxane-water solvate as described in claim 1 having XRD shown in figure 5.