Salts of an FGFR inhibitor
The present invention relates to salt forms of the Fibroblast Growth Factor Receptors (FGFR) inhibitor 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3′,2′:5,6]pyrido[4,3-d]pyrimidin-2-one, including methods of preparation thereof, where the compound is useful in the treatment of FGFR mediated diseases such as cancer.
1. A salt which is an acid salt of 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3′, 2′:5,6]pyrido[4,3-d]pyrimidin-2-one, having the structure:
or a hydrate or solvate thereof, wherein the acid is salicylic acid; wherein the salt is crystalline; and wherein the salt has at least one characteristic XRPD peak selected from about 10.4, about 11.8, about 12.1, about 13.4, and about 13.9 degrees 2-theta.
2. The salt of claim 1 which is a hydrate.
3. The salt of claim 1 which is a solvate.
4. The salt of claim 1 , having an X-ray powder diffraction pattern with characteristic peaks as substantially shown in FIG. 10 .
5. A pharmaceutical composition comprising a salt of claim 1 , and a pharmaceutically acceptable carrier or excipient.
6. A solid oral dosage form comprising the pharmaceutical composition of claim 5 .
7. The salt of claim 1 , having at least two characteristic XRPD peaks selected from about 10.4, about 11.8, about 12.1, about 13.4, and about 13.9 degrees 2-theta.
8. The salt of claim 1 , having at least three characteristic XRPD peaks selected from about 10.4, about 11.8, about 12.1, about 13.4, and about 13.9 degrees 2-theta.
9. The salt of claim 1 , which exhibits a DSC thermogram having an endothermic peak at a temperature of about 212° C.
10. The salt of claim 1 , having a DSC thermogram substantially as depicted in FIG. 11 .