Salts of an LSD1 inhibitor and processes for preparing the same

Patent metadata

Field	Value
Publication number	US-11512064-B2
Application number	US-202117200082-A
Country	US
Kind code	B2
Filing date	Mar 12, 2021
Priority date	Aug 31, 2018
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

The present invention relates to processes and intermediates for preparing 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide, and salts and solid forms thereof, which selectively modulate demethylase. Particular embodiments contemplate compounds and disease indications amenable to treatment by modulation of lysine specific demethylase-1 (LSD1).

First claim

What is claimed is:

1. A process for preparing Compound 1 having the formula:

or a salt thereof, comprising:
deprotecting Compound 2 having the formula:

with A1, wherein A1 is an acid.

2. The process of claim 1 , wherein A1 is hydrochloric acid.

3. The process of claim 1 , wherein the process forms Compound 1 di-hydrochloric acid salt.

4. The process of claim 1 , wherein the deprotecting is performed in the presence of S1, wherein S1 is a protic solvent.

5. The process of claim 4 , wherein S1 is methanol.

6. The process of claim 1 , wherein the deprotecting comprises using about 1 to about 15 molar equivalents of A1 relative to Compound 2.

7. The process of claim 1 , further comprising precipitating Compound 1 from a solution comprising Compound 1 and S2, wherein S2 comprises a solvent and an anti-solvent.

8. The process of claim 1 , wherein Compound 2 is produced by a process comprising: contacting Compound 3 having the formula:

with Compound 4 having the formula:

9. The process of claim 8 , wherein Compound 3 is produced by a process comprising: treating Compound 5 having the formula:

with B1, wherein B1 is a base.

10. The process of claim 9 , wherein B 1 is a metal hydroxide base.

11. The process of claim 9 , wherein B1 is KOH.

12. The process of claim 9 , wherein Compound 5 is produced by a process comprising: reacting Compound 6 having the formula:

with di-tert-butyl dicarbonate.

13. The process of claim 12 , wherein Compound 6 is produced by a process comprising: contacting Compound 7 having the formula:

with Compound 8 having the formula:

in the presence of A2 and RA1, wherein A2 is an acid and RA1 is a reducing agent.

14. The process of claim 13 , wherein A2 is an organic acid.

15. The process of claim 13 , wherein A2 is acetic acid.

16. The process of claim 13 , wherein Compound 7 is produced by a process comprising contacting piperidin-4-one hydrochloride hydrate with 2,2,2-trifluoroacetic anhydride in the presence of B2, wherein B2 is a base.

17. The process of claim 16 , wherein B2 is an amine base.

18. The process of claim 16 , wherein B2 is triethylamine.

19. The process of claim 8 , wherein Compound 4 is produced by a process comprising: treating Compound 9 having the formula:

with A3, wherein A3 is an acid.

20. The process of claim 19 , wherein A3 is an organic acid.

21. The process of claim 19 , wherein A3 is trifluoroacetic acid.

22. A process for preparing Compound 1 having the formula:

or a salt thereof, comprising: deprotecting Compound 12 having the formula:

with A4, wherein A4 is an acid.

23. The process of claim 22 , wherein the salt of Compound 1 is a hydrochloric acid salt.

Assignees

• Incyte Corp

Inventors

• Jia Zhongjiang
• Han Wayne
• Pan Yongchun
• Martin Timothy
• Zhou Jiacheng
• Li Qun

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D205/06

  having one double bond between ring members or between a ring member and a non-ring member · CPC title