Methods of making 2-amino-1-(3-hydroxy-2,6-dimethylphenyl)-5,6-dimethyl-1h-pyrrolo-[2,3-b]pyridine-3-carboxamide, a myt1 inhibitor
AssigneeRepare Therapeutics Inc.
InventorsAngelos DOVLETOGLOU, Robert Charles LIVINGSTON, Jill A. CAPUTO, Sarah M. POUND, Qi GAO
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Abstract
Disclosed are methods for preparing enantioenriched Compound 1, which involve chiral salt resolution of Compound 1, or of intermediate INT If or intermediate INT 1g. Said Compound 1 is useful for the treatment of a disease or condition (e.g., cancer), in particular those diseases or conditions which depend on the activity of membrane-associated tyrosine and threonine-specific cdc2-inhibitory kinase (Myt1).
Claims49
A method of preparing an enantioenriched Compound 1:
- or a salt thereof,
- the method comprising the steps of
- (a) producing an enantioenriched chiral salt of compound INT 1f:
- and
- (b) converting the enantioenriched chiral salt of compound INT 1f to Compound 1 or a salt thereof.
A method of preparing an enantioenriched Compound 1, or a salt thereof, the method comprising the steps of
- (a) producing an enantioenriched chiral salt of compound INT 1g;
- and
- (b) converting the enantioenriched chiral salt of compound INT 1g to Compound 1 or a salt thereof.
A method of preparing an enantioenriched Compound 1, the method comprising the steps of
- (a) producing an enantioenriched chiral salt of Compound 1;
- and
- (b) converting the enantioenriched chiral salt of Compound 1 to Compound 1.
A chiral acid addition salt of compound INT 1f, wherein the chiral acid is (S)-(+)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate;
- (R)-(−)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate;
- (1S)-(+)-3-Bromocamphor-10-sulfonic acid hydrate;
- (1R)-(−)-10-camphorsulfonic acid;
- (1S)-(+)-10-Camphorsulfonic acid;
- (+)-2,3-dibenzoyl-D-tartaric acid;
- (−)-2,3-dibenzoyl-L-tartaric acid;
- (−)-O,O′-di-p-toluoyl-L-tartaric acid;
- (+)-O,O′-di-p-toluoyl-D-tartaric acid;
- (S)-TCYP;
- (R)-TCYP;
- (S)-TRIP;
- or (R)-TRIP.
A chiral acid addition salt of compound INT 1g, wherein the chiral acid is (S)-(+)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate;
- (R)-(−)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate;
- (1S)-(+)-3-Bromocamphor-10-sulfonic acid hydrate;
- (1R)-(−)-10-camphorsulfonic acid;
- (1S)-(+)-10-Camphorsulfonic acid;
- (+)-2,3-dibenzoyl-D-tartaric acid;
- (−)-2,3-dibenzoyl-L-tartaric acid;
- (−)-O,O′-di-p-toluoyl-L-tartaric acid;
- (+)-O,O′-di-p-toluoyl-D-tartaric acid;
- (S)-TCYP;
- or (R)-TCYP.
A chiral acid addition salt of Compound 1, wherein the chiral acid is (S)-(+)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate;
- (R)-(−)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate;
- (1S)-(+)-3-Bromocamphor-10-sulfonic acid hydrate;
- (1R)-(−)-10-camphorsulfonic acid;
- or (1S)-(+)-10-Camphorsulfonic acid.
Dependencies are inferred from the claim text.