Claims for Patent: 12,247,012

Summary for Patent: 12,247,012

Title:	Synthesis of nirogacestat
Abstract:	The present disclosures are directed to processes for synthesizing (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide (“nirogacestat”).
Inventor(s):	Kristin Patterson, Mark Hatcher
Assignee:	SpringWorks Therapeutics Inc
Application Number:	US17/937,283
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,247,012
Patent Claims:	1. A process for preparing a composition comprising Compound 1 or a pharmaceutically acceptable salt thereof which is susceptible to oxidation that is substantially free of Compound 13 comprising the steps of: i) dissolving Compound 11 in a solvent, ii) reacting Compound 9 with 1,1′-carbonyldiimidazole to form Compound 10, and iii) combining Compound 10 with Compound 11 to form a composition comprising Compound 1 or a pharmaceutically acceptable salt thereof, where Compound 1 has the formula 2. The process of claim 1, wherein the solvent is an alcohol of the formula R—OH, wherein R is an alkyl, with the proviso that R is not ethyl. 3. The process of claim 1, wherein the solvent is a primary alcohol, other than ethanol. 4. The process of claim 1, wherein the solvent is a secondary alcohol. 5. The process of claim 1, wherein the solvent is a tertiary alcohol. 6. The process of claim 1, wherein the solvent is 2-methylpropan-1-ol. 7. The process of claim 1, wherein the solvent is propanol. 8. The process of claim 1, wherein the solvent is isopropanol. 9. The process of claim 1, wherein the process further comprises treating Compound 1 with hydrobromic acid. 10. The process of claim 1, wherein the mixture is maintained at a pH less than 6. 11. The process of claim 1, wherein the mixture is maintained at a pH less than 3. 12. A pharmaceutical composition comprising Compound 1 prepared by the process of claim 1, wherein (a) the composition is substantially free of Compound 13 (b) the composition comprises Compound 2 or a pharmaceutically acceptable salt thereof. 13. The process of claim 9, wherein the mixture is warmed to 0-5° C. during hydrobromic acid treatment. 14. The process of claim 1, wherein the process further comprises reacting Compound 1 with an aqueous inorganic acid to form a pharmaceutically acceptable salt of Compound 1. 15. The pharmaceutical composition of claim 12, wherein the composition comprises: (1) 98.0% to 99.9% of Compound 1 or a pharmaceutically acceptable salt thereof; and (2) 0.6% to 0.01% of Compound 2 or a pharmaceutically acceptable salt thereof.