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AssigneePfizer Inc.
InventorsR. Mark Guinn, Subramanian Sam Guhan, Karl K. Ng, Derek L. Tickner, Marcus Douglas Ewing, Clifford N. Meltz, Bryan Li, Kees Pouwer
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This invention relates to the enantiomers of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-y)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl) -phenyl]-1-methyl-1H-quinolin-2-one, prodrugs thereof, and pharmaceutically acceptable salts and solvates of said compounds and said prodrugs, that are useful in the treatment of hyperproliferative diseases, such as cancers, in mammals. The invention also relates to processes for the production of enantiomerically pure or optically enriched (+)- or (−)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl )-phenyl]-1 -methyl-1H-quinol in-2-one enantiomers from a mixture containing two enantiomers using continuous chromatography. The invention further relates to the L-(+)-tartaric acid or (S)-(−)-1 1'-binapthyl-2,2'-diyl hydrogenphosphate salts of (+)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one.
A compound selected from the group consisting of (+)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1 -ynyl)-phenyl]-1-methyl-1 H-quinolin-2-one and (−)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1 -ynyl)-phenyl]-1-methyl-1 H-quinolin-2-one, prodrugs thereof and pharmaceutically acceptable salts and solvates of said compounds and prodrugs.
A process for chromatographically resolving 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-i -ynyl )-phenyl]-1-methyl-1H-quinolin-2-one using continuous chromatography, the continuous chromatography comprising a liquid mobile phase comprising a least one polar solvent and a solid chiral stationary phase comprising a derivatized polysaccharide that is selected from the amylosic and cellulosic class of polysaccharides.
A process for the production of enantiomerically pure or optically enriched 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but- 1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one using simulated moving bed chromatography, the moving bed chromatography comprising a liquid mobile phase comprising a least one polar solvent and a solid chiral stationary phase comprising a derivatized polysaccharide that is selected from the amylosic and cellulosic class of polysaccharides.
The process of claim 25, wherein the separation factor a is about 1.2 to 5.0 47. The process of claim 46, wherein using a temperature of about 25° C. takes
A process for preparing (+)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1 -ynyl)-phenyl]-1 -methyl-1H-quinolin-2-one, L-(+)-tartaric acid comprising treating 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1 -ynyl)-phenyl]-1 -methyl-1 H-quinolin-2-one with L-(+)-tartaric acid.
A process for preparing (+)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1 -ynyl)-phenyl]-1 -methyl-1 H-quinolin-2-one, (S)-(−)-1,1′-binapthyl-2,2′-diyl hydrogenphosphate comprising treating 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1 -ynyl)-phenyl]-1-methyl-1 H-quinolin-2-one with (S)-(−)-1,1 ′-binapthyl-2,2′-diyl hydrogenphosphate.
Dependencies are inferred from the claim text.