Processes for preparing jak inhibitors and related intermediate compounds
AssigneeIncyte Corporation
InventorJiacheng Zhou
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Abstract
The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.
Claims34
The process according to claim 70, further comprising the process of preparing the compound of Formula Ia:
- comprising reacting a compound of Formula II:
- with hydrogen gas in the presence of a hydrogenation catalyst;
- wherein:
- * indicates a chiral carbon;
- R1 is selected from C3-7 cycloalkyl, C1-6 alkyl, and C1-6 fluoroalkyl;
- R2 is cyano;
- and
- P1 is a protecting group.
10-11. (canceled)
The process according to claim 70, further comprising forming a compound of Formula Ia:
- by reacting a compound of Formula I under dehydrating conditions:
- wherein:
- * indicates a chiral carbon;
- R1 is selected from C3-7 cycloalkyl, C1-6 alkyl, and C1-6 fluoroalkyl;
- R2 is —C(═O)—NH2;
- and
- P1 is a protecting group.
14-21. (canceled)
24-50. (canceled)
The process according to claim 70 further comprising preparing a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia:
- comprising passing a composition comprising a racemate of a compound of Formula Ia through a chiral chromatography unit using a mobile phase and collecting the composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia;
- wherein:
- the process of preparing said composition comprising a racemate of a compound of Formula Ia:
- comprises:
- (a) treating a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia with a compound of Formula D-1:
- in the presence of a first base under conditions sufficient to form a compound of Formula IV:
- and
- (b) reacting a compound of Formula IV with a compound of Formula D-1 in the presence of a second base;
- and
- wherein:
- * is a chiral carbon;
- P1 is a protecting group;
- and
- R1 is selected from C3-7 cycloalkyl, C1-6 alkyl, and C1-6 fluoroalkyl.
The process according to claim 70 further comprising preparing a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia:
- comprising passing a composition comprising a racemate of a compound of Formula Ia through a chiral chromatography unit using a mobile phase and collecting a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia;
- wherein:
- the process of preparing said composition comprising a racemate of a compound of Formula Ia:
- comprises treating a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia with a compound of Formula D-1:
- in the presence of a base under conditions sufficient to form said racemate of said compound of Formula Ia;
- and
- wherein:
- * is a chiral carbon;
- P1 is a protecting group;
- and
- R1 is selected from C3-7 cycloalkyl, C1-6 alkyl, and C1-6 fluoroalkyl.
The process according to claim 70 further comprising preparing a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia:
- comprising passing a composition comprising a racemate of a compound of Formula Ia through a chiral chromatography unit using a mobile phase and collecting a composition comprising an enantiomeric excess of the (R)- or (S)-enantiomer of a compound of Formula Ia;
- wherein:
- * is a chiral carbon;
- R1 is selected from C3-7 cycloalkyl, C1-6 alkyl, and C1-6 fluoroalkyl;
- and
- P1 is a protecting group.
61-69. (canceled)
A process of preparing a compound of Formula III:
- comprising reacting a compound of Formula Ia:
- under deprotection conditions to form a compound of Formula III;
- wherein:
- * is a chiral carbon;
- R1 is selected from C3-7 cycloalkyl, C1-6 alkyl, and C1-6 fluoroalkyl;
- and
- P1 is a protecting group.
75-105. (canceled)
Dependencies are inferred from the claim text.