SALTS AND PROCESSES OF PREPARING A PI3K INHIBITOR
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.
2 - 13 . (canceled)
14 . A pharmaceutical composition comprising a salt of claim 1 and a pharmaceutically acceptable carrier.
15 . A method of inhibiting an activity of a PI3K kinase, comprising contacting the kinase with a salt of claim 1 .
16 . The method of claim 15 , wherein the PI3K is PI3Kδ.
17 . The method of claim 16 , wherein said salt is a selective inhibitor for PI3Kδ over one or more of PI3Kα, PI3Kβ, or PI3Kγ.
18 . A method of treating a disease in a patient, wherein said disease is associated with abnormal expression or activity of a PI3K kinase, comprising administering to said patient a therapeutically effective amount of a salt of claim 1 .
19 - 30 . (canceled)
31 . A process of preparing the salt of claim 1 , comprising reacting a compound of Formula I:
with hydrochloric acid to form said salt.
32 - 35 . (canceled)
36 . A process, comprising reacting a compound of Formula XVI:
with formamidine acetate to form a compound of Formula I:
37 - 80 . (canceled)
81 . A compound selected from a compound of Formula XIV:
or a pharmaceutically acceptable salt thereof;
a compound of Formula XV:
or a pharmaceutically acceptable salt thereof;
a compound of Formula XVI:
or a pharmaceutically acceptable salt thereof;
a compound of Formula XIX:
or a pharmaceutically acceptable salt thereof;
a compound of Formula XX:
or a pharmaceutically acceptable salt thereof; and
a compound of Formula XXI:
or a pharmaceutically acceptable salt thereof.
82 - 86 . (canceled)