DESC:The following specification particularly describes the invention and the manner in which it is to be performed:

INTRODUCTION
The present invention provides Benzyl alcohol solvate of Dasatinib.
BACKGROUND OF THE INVENTION
The drug compound having the adopted name “Dasatinib” has a chemical name N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyridiminyl]amino]-5-thiazolecarboxamide, and is structurally represented by Formula I.

Formula I
Dasatinib is sold under the trade name Sprycel®. Dasatinib is an oral dual BCR/ ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblasticjeukemia (Ph+ ALL).
The PCT application WO2005077945 discloses several crystalline forms of Dasatinib which are designated as monohydrate, butanol solvate, ethanol solvate, crystalline neat form (?-6) and crystalline neat form (T1H1-7).
US patent no. 7973045 discloses anhydrous form and various other solvates of dasatinib. US ‘045 also disclose process for the preparation of amorphous dasatinib by evaporating the solvent from the suspension. The solvents used in the process were selected from dimethylformamide, 1, 2-dichlorobenzene, propylene glycol, ethylene glycol, glycerol and benzyl alcohol. Example 56 of US ‘045 discloses preparation of amorphous Dasatinib by slurring in benzyl alcohol and heating.
US20140343073A1 discloses process for the preparation of amorphous form of dasatinib by milling.
WO2017134615A1 disclose Dasatinib (S) – propylene glycol solvate and Dasatinib (R) – propylene glycol solvate.
WO2017002131A1 disclose crystalline 1, 2-propnaediol solvate of Dasatinib.
For a compound to be suitable for use as a therapeutic agent, the physical properties of the compound should be such that they do not negatively impact the effectiveness and cost of a formulated active ingredient.
The inventors of the present invention have surprisingly found a novel crystalline form of dasatinib and process for its preparation.
SUMMARY OF THE INVENTION
In an aspect, the present invention provides crystalline form of benzyl alcohol solvate of Dasatinib.
In an aspect, the present invention provides crystalline form of benzyl alcohol solvate of Dasatinib characterized by PXRD pattern as shown in figure 1.
In an aspect, the present invention provides crystalline form of benzyl alcohol solvate of Dasatinib characterized by PXRD pattern having peaks at about 5.62, 12.37, 17.06, 22.37 and 27.50 ± 0.20 degrees 2-theta and also having peaks at about 11.17, 11.36, 16.73, 18.30 and 24.66 ± 0.20 degrees 2-theta.
In an aspect, the present invention provides processes for the preparation of crystalline form of benzyl alcohol solvate of Dasatinib.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 illustrates the PXRD pattern of crystalline form of benzyl alcohol solvate of Dasatinib.
DETAILED DESCRIPTION
In an aspect, the present invention provides crystalline form of benzyl alcohol solvate of Dasatinib.
In an aspect, the present invention provides crystalline form of benzyl alcohol solvate of Dasatinib characterized by PXRD pattern as shown in figure 1.
In an aspect, the present invention provides crystalline form of benzyl alcohol solvate of Dasatinib characterized by PXRD pattern having peaks at about 5.62, 12.37, 17.06, 22.37 and 27.50 ± 0.20 degrees 2-theta and also having peaks at about 11.17, 11.36, 16.73, 18.30 and 24.66 ± 0.20 degrees 2-theta.
In an aspect, the present invention provides process for the preparation of crystalline form of benzyl alcohol solvate of Dasatinib, comprising the steps of:
a) mixing dasatinib and benzyl alcohol;
b) heating the reaction mixture at 40-90° C;
c) cooling the reaction mixture to a temperature below 35° C;
d) isolating the crystalline form of dasatinib.
In step a) either dasatinib is added to benzyl alcohol or benzyl alcohol is added to dasatinib at temperature of about 0°C to about 50°C, preferably at about 10°C to about 40°C, more preferably at about 25°C to about 35°C. The ratio of dasatinib to benzyl alcohol may vary from about 1:5 to 1:25 by volume. Preferably the ratio is about 1:10 to 1:25 by volume.
Step b) comprises heating the reaction mixture at 40-90° C. In an embodiment, the reaction mixture of step a) is heated at a temperature of about 40°C to about 90 °C, more preferably at about 50°C to about 80 °C and stirring was performed for a time period of about 30 minutes to about 24 hours.
Step c) involves cooling the reaction mixture below 35 oC. In a preferred embodiment, the reaction mixture is cooled to 10-30 oC, more preferably to about 20°C to 30°C. The reaction mixture is maintained for a sufficient time to ensure the formation of benzyl alcohol solvate of dasatinib. The crystalline benzyl alcohol solvate of dasatinib is isolated in a manner known per se, which include, but not limited to filtration by gravity or by suction/vacuum, distillation, centrifugation, or slow evaporation or the like. In an embodiment, crystalline benzyl alcohol solvate of dasatinib may be isolated by filtration under vacuum and suction drying at a temperature of about 20°C to about 30°C.
In one embodiment, the present invention provides pharmaceutical composition comprising crystalline form of benzyl alcohol solvate of Dasatinib and at least one pharmaceutically acceptable excipient.
Pharmaceutically acceptable excipients include, but are not limited to, suitable surface modifiers. Such excipients include various polymers, low molecular weight oligomers, natural products, and surfactants.
The following examples further illustrate the invention but should not be construed in any way limiting its scope.
General description of the PXRD equipment:
Instrumental parameters.
Model & Detector
Model Bruker AXS, D8 Discover
Detector PSD-Lynxeye_XE
Instrument Setting
Goniometer Theta/Theta Vertical
Mode of Collection Reflection
Measuring circle 560 mm
Radiation Cu Ka (Wavelength =1.5418 Å)
Scan Parameters
Voltage (kV) and Current (mA) 40, 40
Scan range (°2?) 3-40
Step size (°2?) 0.02
Time/step (s) 0.9
Run Time (min) 30
Scan mode Continuous
Divergent slit (°) 0.3
Anti-scattering slit (mm) 8.0
Rotation/min On

EXAMPLES
Example 1: Preparation of benzyl alcohol solvate of dasatinib
2.25 g of dasatinib and 35 mL of benzyl alcohol were taken in an EasyMax reactor at 25 to 30 oC. The contents were stirred and heated to 65oC and maintained for 1-2 hours. The contents were then cooled to 20-30 oC. The obtained material was filtered and dried in vacuum tray dryer at 45oC to afford benzyl alcohol solvate of dasatinib characterized by PXRD pattern as shown in figure 1.
,CLAIMS:We Claim:
1. A crystalline form of benzyl alcohol solvate of Dasatinib.
2. The benzyl alcohol solvate of Dasatinib according to claim 1, characterized by X-ray powder diffraction pattern having peaks at about 5.62, 12.37, 17.06, 22.37 and 27.50 ± 0.20°2?.
3. The benzyl alcohol solvate of Dasatinib according to claim 2, characterized by X-ray powder diffraction pattern having additional peaks at about 11.17, 11.36, 16.73, 18.30 and 24.66 ± 0.20° 0.2° 2?.
4. A process for the preparation of crystalline form of benzyl alcohol solvate of Dasatinib, comprising the steps of:
a) mixing dasatinib and benzyl alcohol;
b) heating the reaction mixture at 40-90° C;
c) cooling the reaction mixture to a temperature below 35° C;
d) isolating the crystalline form of dasatinib.