Claims for Patent: 10,550,098

Summary for Patent: 10,550,098

Title:	Pyridin-2(1H)-one quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
Abstract:	The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, U, W1, W2, W3, R1-R6, and R9 are described herein.
Inventor(s):	Jian Lin, Anna Ericsson, Ann-Marie Campbell, Gary Gustafson, Zhongguo Wang, R. Bruce Diebold, Susan Ashwell, David R. Lancia, Jr., Justin Andrew Caravella, Wei Lu
Assignee:	Forma Therapeutics Inc
Application Number:	US16/290,240
Patent Claims:	1. A composition comprising Compound I-13 obtained by a process comprising a step of reacting Intermediate II-1 or a salt thereof and Intermediate III-1: 2. The composition of claim 1, wherein the process further comprises obtaining Intermediate III-1 from 5-fluoro-6-oxo-1,6-dihydropyridine-2-carbonitrile. 3. The composition of claim 2, wherein the process further comprises obtaining 5-fluoro-6-oxo-1,6-dihydropyridine-2-carbonitrile from 6-cyano-3-fluoropyridin-2-yl acetate. 4. The composition of claim 3, wherein the process further comprises obtaining 6-cyano-3-fluoropyridin-2-yl acetate from 2-cyano-5-fluoropyridine-1-oxide. 5. The composition of claim 4, wherein the process further comprises obtaining 2-cyano-5-fluoropyridine-1-oxide from 5-fluoropicolinonitrile. 6. The composition of claim 1, wherein the process further comprises obtaining Intermediate II-1, or a salt thereof, from (R)—N—((S)-1-(2,6-dichloroquinolin-3-yl)ethyl)-2-methylpropane-2-sulfinamide. 7. The composition of claim 6, wherein the process further comprises obtaining (R)—N—((S)-1-(2,6-dichloroquinolin-3-yl)ethyl)-2-methylpropane-2-sulfinamide from (R,E)-N-((2,6-dichloroquinolin-3-yl)methylene)-2-methylpropane-2-sulfinamide. 8. The composition of claim 7, wherein the process further comprises obtaining (R,E)-N-((2,6-dichloroquinolin-3-yl)methylene)-2-methylpropane-2-sulfinamide from 2,6-dichloroquinoline-3-carbaldehyde. 9. A method of preparing compound I-13: wherein the method comprises a step of reacting Intermediate II-1, or a salt thereof, and Intermediate III-1: to form compound I-13. 10. The method of claim 9, wherein the method further comprises a step of preparing Intermediate III-1: by a process comprising a step of reacting 5-fluoro-6-oxo-1,6-dihydropyridine-2-carbonitrile: with a suitable methylating agent to form Intermediate III-1. 11. The method of claim 10, wherein the method further comprises a step of preparing 5-fluoro-6-oxo-1,6-dihydropyridine-2-carbonitrile: by a process comprising a step of reacting 6-cyano-3-fluoropyridin-2-yl acetate: with a suitable base to form 5-fluoro-6-oxo-1,6-dihydropyridine-2-carbonitrile. 12. The method of claim 11, wherein the method further comprises a step of preparing 6-cyano-3-fluoropyridin-2-yl acetate: by a process comprising a step of reacting 2-cyano-5-fluoropyridine-1-oxide; with acetic anhydride to form 6-cyano-3-fluoropyridin-2-yl acetate. 13. The method of claim 12, wherein the method further comprises a step of preparing 2-cyano-5-fluoropyridine-1-oxide: by a process comprising a step of reacting 5-fluoropicolinonitrile: with a suitable oxidizing agent to form 2-cyano-5-fluoropyridine-1-oxide. 14. The method of claim 9, wherein the method further comprises a step of preparing Intermediate II-1, or a salt thereof: by a process comprising a step of reacting (R)—N—((S)-1-(2,6-dichloroquinolin-3-yl)ethyl)-2-methylpropane-2-sulfinamide: with a suitable acid to form Intermediate II-1, or a salt thereof. 15. The method of claim 14, wherein the method further comprises a step of preparing (R)—N—((S)-1-(2,6-dichloroquinolin-3-yl)ethyl)-2-methylpropane-2-sulfinamide: by a process comprising a step of reacting (R,E)-N-((2,6-dichloroquinolin-3-yl)methylene)-2-methylpropane-2-sulfinamide: with MeMgBr to form (R)—N—((S)-1-(2,6-dichloroquinolin-3-yl)ethyl)-2-methylpropane-2-sulfinamide. 16. The method of claim 15, wherein the method further comprises a step of preparing (R,E)-N-((2,6-dichloroquinolin-3-yl)methylene)-2-methylpropane-2-sulfinamide: by a process comprising a step of reacting 2,6-dichloroquinoline-3-carbaldehyde: with: to form (R,E)-N-((2,6-dichloroquinolin-3-yl)methylene)-2-methylpropane-2-sulfinamide. 17. The method of claim 10, wherein the suitable methylating agent is MeI. 18. The method of claim 11, wherein the suitable base is K2CO3. 19. The method of claim 13, wherein the suitable oxidizing agent is m-CPBA. 20. The method of claim 14, wherein the suitable acid is HCl. 21. A composition comprising Compound I-13: and at least one compound selected from the group consisting of Intermediate II-1 or a salt thereof and Intermediate III-1: 22. The composition of claim 21 comprising Compound I-13 and Intermediate II-1 or a salt thereof. 23. The composition of claim 21 comprising Compound I-13 and Intermediate III-1. 24. The composition of claim 21 comprising Compound I-13, Intermediate II-1 or a salt thereof, and Intermediate III-1. 25. The composition of claim 21, wherein Compound I-13 is obtained by a process comprising a step of reacting Intermediate II-1 or a salt thereof and Intermediate III-1.