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US 11,685,731 B2Granted
Processes of preparing a JAK1 inhibitor
AssigneeIncyte Corporation
InventorsJiacheng Zhou, Yingrui Dai, Zhongjiang Jia, Yongchun Pan, James M. Parks, Anthony J. Tomaine, Jianji Wang, Aibin Zhang
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Abstract
The present application provides processes for preparing 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H, 1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, and phosphoric acid salt thereof, which is useful as a selective (Janus kinase 1) JAK1 inhibitor, as well as salt forms and intermediates related thereto.
Claims80
A process of preparing
- or a salt thereof, comprising reacting
- to form Compound 1 free base, or a salt thereof.
A process of preparing a compound of Formula A:
- comprising reacting 3,5-dimethyl-1H,1′H-4,4′-bipyrazole with a compound of Formula B:
- wherein Pg1 is an amine protecting group.
A process of preparing Compound 1 phosphoric acid salt:
- comprising:
- reacting 3,5-dimethyl-1H,1′H-4,4′-bipyrazole with tent-butyl 3-(cyanomethylene)azetidine-1-carboxylate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene to form the compound of Formula A-1:
- deprotecting the compound of Formula A-1 to form the compound of Formula C-1:
- or a salt thereof;
- reacting the compound of Formula C-1 with triethylamine to form the free base form of the compound of Formula C-1;
- reacting the free base form of the compound of Formula C-1 with Compound 1a:
- in the presence of sodium bicarbonate and lithium chloride to form Compound 1:
- reacting Compound 1 with hydrochloric acid to form Compound 1 hydrochloric acid salt:
- reacting Compound 1 hydrochloric acid salt with potassium bicarbonate to form the free base form of Compound 1;
- and
- reacting the free base form of Compound 1 with phosphoric acid to form the Compound 1 phosphoric acid salt.
8 more elements
Dependencies are inferred from the claim text.