Processes for the preparation of selective estrogen receptor degraders
AssigneeEli Lilly and Company
InventorsAlonso Jose ARGUELLES DELGADO, Boris Arnoldovich CZESKIS, Mai Khanh Nguyen HAWK, Douglas Patton KJELL, Yu LU, Nicholas Andrew MAGNUS, David Michael REMICK
Life of this patent
Estimating the term…
Abstract
Disclosed are methods of making selective estrogen receptor degraders (SERDs) of Formula A, as well as intermediates thereof, salts thereof including a pharmaceutically acceptable salt, and pharmaceutical compositions thereof: wherein either R1 or R2 is independently Cl, F, —CF3, or —CH3, and the other is H; and R7 is H or PG.
Claims14
1-19. (canceled)
A compound of Formula A
- or a pharmaceutically acceptable salt thereof, wherein either R1 or R2 is independently Cl, F, —CF3, or —CH3, and the other is H;
- and R7 is H or PG, wherein the compound of Formula A is at least 98% area and containing less than 1% area of one or more dihydroquinoline or quinoline based impurities.
A compound of Formula A
- or a pharmaceutically acceptable salt thereof, wherein either R1 or R2 is independently Cl, F, —CF3, or —CH3, and the other is H;
- and R7 is H or PG, obtainable by reacting a compound of structure 8:
- or a salt thereof, in a solvent with an amine of structure 9
- or a salt thereof, and a reducing agent.
A compound of Formula A
- or a pharmaceutically acceptable salt thereof, wherein either R1 or R2 is independently Cl, F, —CF3, or —CH3, and the other is H;
- and R7 is H or PG, obtainable by reacting a compound of structure 8:
- or a salt thereof, in a solvent with an amine of structure 9
- or a salt thereof, and a reducing agent, wherein the compound of Formula A has an enantiomeric excess of at least about 92%.
A compound of Formula A
- or a pharmaceutically acceptable salt thereof, wherein either R1 or R2 is independently Cl, F, —CF3, or —CH3, and the other is H;
- and R7 is H or PG, which contains a C3-C7 alcohol.
The process according to claim 1, wherein R7 is H.
The process according to claim 1, wherein R1 is H, and R2 is CF3.
The process according to claim 1, wherein PG is methyl.
A compound of Formula B
- or a pharmaceutically acceptable salt thereof, that is at least 98.5% area.
A pharmaceutical composition comprising a compound made according to the process of claim 1, in combination with at least one pharmaceutically acceptable excipient, carrier, or diluent.
(canceled)
Dependencies are inferred from the claim text.