# US 11,993,588 B2 · Crystalline forms of a MAGL inhibitor

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,993,588 B2
- Document ID: US11993588B2
- Status: Granted
- Kind: B2
- Application number: 17/469,535
- Filed: 2021-09-08
- Published: 2022-07-28
- Granted: 2024-05-28
- Earliest claimed: 2016-11-16
- Assignees: H. Lundbeck A/S
- Applicants: H. Lundbeck A/S
- Inventors: Cheryl A. Grice; Todd K. Jones; Kurt G. Grimm; Jacqueline Lorayne Blankman; Channing Rodney Beals
- Web page: https://patentgrep.com/patent/US11993588B2

## CPC

- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 403/10: linked by a carbon chain containing aromatic rings
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07C 57/15: Fumaric acid
- C07D 295/205: Radicals derived from carbonic acid
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Described herein is the MAGL inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, including crystalline forms and pharmaceutically acceptable salts and solvates thereof.

## Claims

### Claim 1

A crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base, wherein the crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 7.8° 2-Theta, 12.0° 2-Theta, 18.5° 2-Theta, 19.0° 2-Theta, 19.6° 2-Theta and 21.2° 2-Theta.

### Claim 2

A crystalline form 1 of 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate mono-hydrochloride salt, wherein the crystalline form 1 has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.4° 2-Theta, 14.9° 2-Theta, 16.9° 2-Theta, 18.4° 2-Theta, and 20.9° 2-Theta.

### Claim 3

A crystalline form 2 of 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate mono-hydrochloride salt, wherein the crystalline form 2 has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 8.6° 2-Theta, 14.3° 2-Theta, 15.6° 2-Theta, 19.0° 2-Theta, 19.8° 2-Theta, and 20.7° 2-Theta.

### Claim 4

A crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate bis-hydrochloride salt, wherein the crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate bis-hydrochloride salt has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 6.4° 2-Theta, 12.0° 2-Theta, 12.5° 2-Theta, 14.3° 2-Theta, 18.5° 2-Theta, and 22.8° 2-Theta.

### Claim 5

A crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate fumarate salt, wherein the crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate fumarate salt has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 13.6° 2-Theta, 14.1° 2-Theta, 14.3° 2-Theta, 20.0° 2-Theta, and 21.9° 2-Theta.

### Claim 6

A crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate mesylate salt, wherein the crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate mesylate salt has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 8.6° 2-Theta, 12.4° 2-Theta, 14.6° 2-Theta, 16.5° 2-Theta, 17.7° 2-Theta, and 19.7° 2-Theta.