Crystalline dasatinib process

Patent metadata

Field	Value
Publication number	US-2016264565-A1
Application number	US-201415033910-A
Country	US
Kind code	A1
Filing date	Apr 24, 2014
Priority date	Nov 8, 2013
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present invention relates to a process for preparation of crystalline Form-SDI of Dasatinib (I).

Said crystalline Form-SDI of Dasatinib is characterized by X-ray powder diffraction pattern comprising of at least seven 2θ° peaks selected from the XRPD peak set of 5.8, 11.5, 12.7, 13.2, 17.3, 17.5, 18.1, 20.1, 20.5, 22.1, 25.4, 26.6, 26.8±0.20 2θ°; IR spectrum having at least five absorption peaks selected from about 3390 cm −1 , 2923 cm −1 , 1621 cm −1 , 1615 cm −1 , 1537 cm −1 , 1316 cm −1 , 1061 cm −1 , 815 cm −1 and 783 cm −1 ; and DSC isotherm comprising at least two endothermic peaks ranging between −130° C. to 150° C., 160° C. to 175° C. or 280° C. to 290° C.
The pharmaceutical compositions of the crystalline Form-SDI of Dasatinib or its hydrate thereof may be useful as an anti-cancer agent.

First claim

We claim:

1 . A process for preparing crystalline Form-SDI of Dasatinib (I),

comprising the steps of:
a) Reacting N-(2-chloro-6-methylphenyl)-2-[6-chloro-2-methyl-4-pyrimidinyl) amino]-5-thiazole carboxamide (II) with 1-(3-Hydroxy)ethylpiperazine (III) in solvent 3-methylbutan-1-ol in absence of base;

b) Raising the temperature of reaction mixture to a temperature above 100° C.;
c) Cooling the reaction mixture to room temperature;
d) Filtering the reaction mass and washing it with 3-methylbutan-1-ol;
e) Optionally, treating the mass obtained from step d) with X—CH 2 —CH 2 —CH 2 —OH in presence of an organic base and 3-methylbutan-1-ol; wherein X is halogen;
f) Isolating the crystalline Form-SDI of Dasatinib (I).

2 . A process for preparing crystalline Form-SDI of Dasatinib according to claim 1 , wherein the organic base used in step e) is an amine or nitrogen-containing heterocyclic compound selected from diisopropyl ethyl amine, pyridine, methyl amine, trimethylamine or triethyl amine.

3 . A process for preparing crystalline Form-SDI of Dasatinib according to claim 1 , wherein step e) of treating the mass obtained from step d) with X—CH 2 —CH 2 —OH in presence of an organic base and 3-methylbutan-1-ol, further comprise the steps of—
i. Heating the reaction mixture to a temperature above 60° C.;
ii. Stirring of the reaction mixture for time ranging from 5-15 hrs;
iii. Cooling of the reaction mass to RT.

4 . A process for preparing crystalline Form-SDI of Dasatinib according to claim 1 , wherein the crystalline Form-SDI, isolated from step f) is further reacted to obtain pharmaceutically acceptable salts of Dasatinib selected from Dasatinib Glucuronate (A) or Dasatinib hydrochloride (B).

5 . A process for preparing pharmaceutically acceptable salts of Dasatinib according to claim 4 , wherein isolation of the pharmaceutically acceptable salt involves the treatment of the reaction mass with an organic solvent characterized by boiling point of less than 70° C.

6 . Crystalline Form-SDI of Dasatinib, synthesized according to the process of claim- 1 , wherein the crystalline Form-SDI is characterized by X-ray powder diffraction pattern comprising of at least seven 2θ° peaks selected from the XRPD peak set of 5.8, 11.5, 12.7, 13.2, 17.3, 17.5, 18.1, 20.1, 20.5, 22.1, 25.4, 26.6, 26.8±0.20 2θ°.

7 . Crystalline Form-SDI of Dasatinib, characterized by X-ray powder diffraction pattern comprising of at least seven 2θ° peaks selected from the XRPD peak set of 5.8, 11.5, 12.7, 13.2, 17.3, 17.5, 18.1, 20.1, 20.5, 22.1, 25.4, 26.6, 26.8±0.20 2θ°; IR spectrum having at least five absorption peaks selected from about 3390 cm −1 , 2923 cm −1 , 1621 cm −1 , 1615 cm −1 , 1537 cm −1 , 1316 cm −1 , 1061 cm −1 , 815 cm −1 and 783 cm −1 ; and DSC isotherm comprising at least two endothermic peaks ranging between—
a) 130° C. to 150° C.,
b) 160° C. to 175° C. or
c) 280° C. to 290° C.

8 . Crystalline Form-SDI of Dasatinib according to claim- 7 , wherein the Crystalline Form-SDI is characterized by 3-methylbutan-1-ol content in range of 10-16% w/w.

9 . Crystalline Form-SDI of Dasatinib according to claim 7 , characterized by X-ray powder diffraction pattern, substantially according to FIG. 1 or, exhibiting a doublet diffraction angle peak at 23.6 and 23.8±0.20 2θ°, IR absorption spectrum substantially according to FIG. 2 and DSC isothermal pattern substantially according to FIG. 3 .

10 . A pharmaceutical composition comprising Crystalline Form-SDI of Dasatinib or its hydrate thereof, together with at least one or more pharmaceutically acceptable excipients.

Assignees

• Shilpa Medicare Ltd

Inventors

• Rampalli Sriram
• Pothana Pradeep
• Garbapu Suresh
• Purohit Prashant
• Chaturvedi Akshaykant

Classifications

• C07H3/02

  Monosaccharides · CPC title

• C07D417/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title