Solid forms of a toll-like receptor modulator
The present invention provides crystalline forms, solvates and hydrates of 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one, and methods of making.
1. A crystalline Form II of Compound I having the structure:
characterized by an X-ray powder diffraction (XRPD) pattern comprising three peaks at 4.6, 9.2, 15.8, 17.8, 18.3, 19.2, 19.9, 22.4, 25.5 or 29.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
2. The crystalline form of claim 1 , characterized by an XRPD pattern comprising four peaks at 4.6, 9.2, 15.8, 17.8, 18.3, 19.2, 19.9, 22.4, 25.5 or 29.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
3. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at 4.6, 9.2, 15.8, 17.8, 18.3, 19.2, 19.9, 22.4, 25.5 and 29.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
4. The crystalline form of claim 1 , characterized by one or more differential scanning calorimetry (DSC) endotherms at about 98° C. or about 253° C.
5. The crystalline form of claim 1 , characterized by DSC endotherms at about 98° C. and about 253° C.
6. A crystalline Form III of Compound I having the structure:
characterized by an X-ray powder diffraction (XRPD) pattern comprising three peaks at 5.0, 10.1, 16.9, 20.3, 21.5, 22.0, 23.9 or 25.2 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
7. The crystalline form of claim 6 , characterized by an XRPD pattern comprising four peaks at 5.0, 10.1, 16.9, 20.3, 21.5, 22.0, 23.9 or 25.2 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
8. The crystalline form of claim 6 , characterized by an XRPD pattern comprising peaks at 5.0, 10.1, 15.2, 16.9, 20.3, 21.5, 22.0, 23.9, 25.2 and 29.4 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
9. The crystalline form of claim 6 , characterized by a differential scanning calorimetery (DSC) endotherm at about 181° C.
10. A method of preparing a crystalline Form II of the Compound I of claim 1 , comprising:
forming a mixture comprising a Form I of Compound I characterized by an XRPD pattern comprising three peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.19, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ, wherein the XRPD is made using CuK α1 radiation, and chloroform, under conditions suitable to prepare form II of Compound I.
11. A method of preparing a crystalline Form III of the Compound I of claim 6 , comprising:
heating a Form I of Compound I, characterized by an XRPD pattern comprising three peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.19, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ, wherein the XRPD is made using CuK α1 radiation, to a temperature of from about 130° C. to about 190° C. thereby preparing Form III.
12. The method of claim 11 , further comprising cooling Form III to room temperature.
13. A crystalline Form II of Compound I having the structure:
characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.6, 18.3, 19.9, 22.4, and 25.5 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
14. The crystalline form of claim 13 , characterized by differential scanning calorimetry (DSC) endotherms at about 98° C. and about 253° C.
15. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound I of claim 13 , and a pharmaceutically acceptable carrier or excipient.
16. A crystalline Form II of Compound I having the structure:
characterized by an X-ray powder diffraction (XRPD) pattern comprising three peaks at 9.2, 15.8, 17.8, 19.2, or 29.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
17. The crystalline form of claim 16 , characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.2, 15.8, 17.8, 19.2, and 29.1 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
18. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound I of claim 16 , and a pharmaceutically acceptable carrier or excipient.
19. A crystalline Form III of Compound I having the structure:
characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.0, 21.5, and 22.0 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
20. The crystalline form of claim 19 , characterized by an XRPD pattern further comprising an additional peak at 10.1, 16.9, 20.3, 23.9 or 25.2 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
21. The crystalline form of claim 19 , characterized by an XRPD pattern further comprising two additional peaks at 10.1, 16.9, 20.3, 23.9 or 25.2 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
22. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound I of claim 19 , and a pharmaceutically acceptable carrier or excipient.