Salts and processes of preparing a PI3K inhibitor
View Patent ↗The present application provides processes for preparing (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, which is useful as an inhibitor phosphoinositide 3-kinase-delta (PI3Kδ), as well as a salt form and intermediates related thereto.
1. A salt which is (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one hydrochloric acid salt, that is crystalline, having at least four XRPD peaks, in terms of 2-theta, selected from about 11.3°, about 16.4°, about 21.0°, about 23.0°, about 28.1°, about 31.2°, and about 32.8°.
2. The salt of claim 1 that is a 1:1 stoichiometric ratio of (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one to hydrochloric acid.
3. The salt of claim 1 characterized by a DSC thermogram having an endothermic peak at about 207° C.
4. The salt of claim 1 having a DSC thermogram substantially as shown in FIG. 1 .
5. The salt of claim 1 having a TGA thermogram substantially as shown in FIG. 2 .
6. The salt of claim 1 having at least five XRPD peaks, in terms of 2-theta, selected from about 11.3°, about 16.4°, about 21.0°, about 23.0°, about 28.1°, about 31.2°, and about 32.8°.
7. The salt of claim 1 having an XRPD profile substantially as shown in FIG. 3 .
8. A pharmaceutical composition comprising a salt of claim 1 and a pharmaceutically acceptable carrier.