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 selected from L-(+)-tartaric acid and D-(−)-tartaric acid, wherein the salt is crystalline, and wherein:
the salt is 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 L-(+)-tartrate having at least one characteristic X-ray powder diffraction peak selected from about 3.8, about 8.5, about 9.1, about 10.3, and about 12.0 degrees 2-theta; or
the salt is 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 D-(−)-tartrate having at least one characteristic XRPD peaks selected from about 7.4, about 10.5, about 12.9, about 13.6, about 14.8, and about 16.4 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 , wherein the salt is 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 L-(+)-tartrate.
5. The salt of claim 1 , wherein the salt is 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 D-(−)-tartrate.
6. The salt of claim 4 , having an X-ray powder diffraction pattern with characteristic peaks as substantially shown in FIG. 6 .
7. The salt of claim 5 , having an X-ray powder diffraction pattern with characteristic peaks as substantially shown in FIG. 2 .
8. A pharmaceutical composition comprising a salt of claim 1 , and a pharmaceutically acceptable carrier or excipient.
9. A solid oral dosage form comprising the pharmaceutical composition of claim 8 .
10. The salt of claim 4 , having at least two characteristic X-ray powder diffraction peaks selected from about 3.8, about 8.5, about 9.1, about 10.3, and about 12.0 degrees 2-theta.
11. The salt of claim 4 , having at least three characteristic X-ray powder diffraction peaks selected from about 3.8, about 8.5, about 9.1, about 10.3, and about 12.0 degrees 2-theta.
12. The salt of claim 5 , having at least two characteristic X-ray powder diffraction peaks selected from about 7.4, about 10.5, about 12.9, about 13.6, about 14.8, and about 16.4 degrees 2-theta.
13. The salt of claim 5 , having at least three characteristic X-ray powder diffraction peaks selected from about 7.4, about 10.5, about 12.9, about 13.6, about 14.8, and about 16.4 degrees 2-theta.