# US 12,180,158 B1 · Crystalline fumarate salts of n-ethyl-2-(5-fluoro-1H-indol-3-yl)-n-methylethan-1-amine

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- Number: US 12,180,158 B1
- Document ID: US12180158B1
- Status: Granted
- Kind: B1
- Application number: 18/368,124
- Filed: 2023-09-14
- Granted: 2024-12-31
- Earliest claimed: 2023-08-03
- Assignees: Gilgamesh Pharmaceuticals, Inc.
- Applicants: Gilgamesh Pharmaceuticals, Inc.
- Inventors: Andrew Carry Kruegel; William Leong; Yameng He; Lauren MacEachern
- Web page: https://patentgrep.com/patent/US12180158B1

## CPC

- C07D 209/14: Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- C07D 209/16: Tryptamines
- A61P 25/24: Antidepressants
- A61P 25/30: for treating abuse or dependence
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure relates to a crystalline salt selected from crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine fumarate and crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hydrochloride, methods of preparing them, and uses thereof for treating mood disorders. In addition, the present disclosure relates to polymorphs of the aforementioned salts. Further, the present disclosure relates to an oil or amorphous form of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine, methods of preparing the same, and uses thereof for treating mood disorders.

## Claims

### Claim 1

A crystalline salt of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine comprising crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine fumarate.

### Claim 2 (depends on 1)

The crystalline salt of claim 1, which is crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine monofumarate Form 1.

### Claim 3 (depends on 2)

The crystalline salt of claim 2 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 17.03±0.50, 17.46±0.50, 19.97±0.50, 21.47±0.50, and 23.18±0.50 degrees 2θ.

### Claim 4 (depends on 2)

The crystalline salt of claim 2 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 17.03±0.50, 17.46±0.50, 18.30±0.50, 19.97±0.50, 21.09±0.50, 21.47±0.50, 22.22±0.50, 23.18±0.50, 23.75±0.50, and 28.67±0.50 degrees 2θ.

### Claim 5 (depends on 2)

The crystalline salt of claim 2 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation substantially as depicted in FIG. 8.

### Claim 6 (depends on 2)

The crystalline salt of claim 2 characterized by a DSC thermogram having at least one endotherm with a peak temperature of about 126° C.

### Claim 7 (depends on 2)

The crystalline salt of claim 2 characterized by a DSC thermogram substantially as depicted in FIG. 10.

### Claim 8 (depends on 1)

The crystalline salt of claim 1, which is crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine monofumarate Form 2.

### Claim 9 (depends on 8)

The crystalline salt of claim 8 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 7.09±0.50, 11.24±0.50, 21.12±0.50, 23.12±0.50, and 28.25±0.50 degrees 2θ.

### Claim 10 (depends on 8)

The crystalline salt of claim 8 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 7.09±0.50, 11.05±0.50, 11.24±0.50, 11.80±0.50, 17.43±0.50, 21.12±0.50, 23.12±0.50, 23.73±0.50, 25.12±0.50, and 28.25±0.50 degrees 2θ.

### Claim 11 (depends on 8)

The crystalline salt of claim 8 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation substantially as depicted in FIG. 11.

### Claim 12 (depends on 8)

The crystalline salt of claim 8 characterized by a DSC thermogram having at least one peak temperature selected from the group consisting of about 92° C., about 101° C., and about 126° C.

### Claim 13 (depends on 8)

The crystalline salt of claim 8 characterized by a DSC thermogram substantially as depicted in FIG. 13.

### Claim 14 (depends on 1)

The crystalline salt of claim 1, which is crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hemifumarate Form 1.

### Claim 15 (depends on 14)

The crystalline salt of claim 14 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 5.79±0.50, 11.55 0.50, 17.96±0.50, 18.49±0.50, and 22.48±0.50 degrees 2θ.

### Claim 16 (depends on 14)

The crystalline salt of claim 14 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 5.79±0.50, 11.55±0.50, 16.28±0.50, 17.35±0.50, 17.96±0.50, 18.49±0.50, 19.23±0.50, 21.58±0.50, 22.48±0.50, and 23.59±0.50 degrees 2θ.

### Claim 17 (depends on 14)

The crystalline salt of claim 14 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation substantially as depicted in FIG. 14.

### Claim 18 (depends on 14)

The crystalline salt of claim 14 characterized by a DSC thermogram having at least one peak temperature selected from the group consisting of about 152° C., about 154° C., and about 161° C.

### Claim 19 (depends on 14)

The crystalline salt of claim 14 characterized by a DSC thermogram substantially as depicted in FIG. 16.

### Claim 20 (depends on 1)

The crystalline salt of claim 1, which is crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hemifumarate Form 2.

### Claim 21 (depends on 20)

The crystalline salt of claim 20 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 7.54±0.50, 17.04±0.50, 19.78±0.50, 20.46±0.50, and 23.43±0.50 degrees 2θ.

### Claim 22 (depends on 20)

The crystalline salt of claim 20 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation comprising peaks at 7.54±0.50, 12.86±0.50, 13.05±0.50, 16.74±0.50, 17.04±0.50, 19.78±0.50, 20.27±0.50, 20.46±0.50, 21.66±0.50, and 23.43±0.50 degrees 2θ.

### Claim 23 (depends on 20)

The crystalline salt of claim 20 characterized by an X-ray powder diffraction pattern measured using Cu K-alpha radiation substantially as depicted in FIG. 17.

### Claim 24

A mixture comprising at least two of the following crystalline salts: crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine monofumarate Form 1, crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine monofumarate Form 2, crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hemifumarate Form 1, and crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hemifumarate Form 2.

### Claim 25

A solid form of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine comprising any one or more crystalline forms of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine fumarate.

### Claim 26 (depends on 25)

The solid form of claim 25 comprising (a) crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine monofumarate Form 1, crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine monofumarate Form 2, or a mixture thereof or (b) crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hemifumarate Form 1, crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine hemifumarate Form 2, or a mixture thereof.

### Claim 27 (depends on 25)

The solid form of claim 25 comprising at least 50% by weight of the crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine fumarate.

### Claim 28 (depends on 25)

The solid form of claim 25 comprising at least 90% by weight of the crystalline N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine fumarate.

### Claim 29

A pharmaceutical composition comprising any one or more crystalline forms of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine fumarate and a pharmaceutically acceptable carrier.

### Claim 30 (depends on 29)

A method of treating a mood disorder in a subject in need of such treatment comprising administering to said subject a therapeutically effective amount of the composition of claim 29.