# US 11,993,606 B2 · Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof

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- Number: US 11,993,606 B2
- Document ID: US11993606B2
- Status: Granted
- Kind: B2
- Application number: 18/453,085
- Filed: 2023-08-21
- Published: 2023-12-14
- Granted: 2024-05-28
- Earliest claimed: 2015-10-16
- Assignees: AbbVie Inc.
- Applicants: AbbVie Inc.
- Inventors: Mohamed-Eslam F. Mohamed; Ahmed A. Othman; Aileen L. Pangan; In-Ho Song; Ben Klünder; Jeffrey W. Voss; Robert J. Padley; Heidi S. Camp
- Web page: https://patentgrep.com/patent/US11993606B2

## CPC

- C07D 487/14: Ortho-condensed systems
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/38: Cellulose; Derivatives thereof
- C07D 487/04: Ortho-condensed systems
- 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)
- 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 processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis and various spondyloarthritic conditions, including types of axial spondyloarthritis (axSpA)), kits, methods of synthesis, and products-by-process. In various aspects, provided are methods for treating active non-radiographic axSpA (nr-axSpA) and methods for treating active ankylosing spondylitis (AS).

## Claims

### Claim 1

A method of treating a human patient having active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1), wherein the therapeutically effective amount is 15 mg.

### Claim 2 (depends on 1)

The method of claim 1, wherein the patient is an adult patient.

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).

### Claim 4 (depends on 1)

The method of claim 1, wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.

### Claim 5 (depends on 1)

The method of claim 1, wherein the 15 mg of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C, wherein Freebase Hydrate Form C has an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, 20.9±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.

### Claim 6 (depends on 1)

The method of claim 1, wherein the method results in an Assessment of SpondyloArthritis International Society 20 (ASAS20) response at 14 weeks after the first daily administration.

### Claim 7 (depends on 6)

The method of claim 6, wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).

### Claim 8 (depends on 6)

The method of claim 6, wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.

### Claim 9

A method of treating a human patient having active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount of(3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the method results in an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at 14 weeks after the first daily administration.

### Claim 10 (depends on 9)

The method of claim 9, wherein the patient is an adult patient.

### Claim 11 (depends on 9)

The method of claim 9, wherein the patient has had an inadequate response or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs).

### Claim 12 (depends on 9)

The method of claim 9, wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.

### Claim 13 (depends on 9)

The method of claim 9, wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C, wherein Freebase Hydrate Form C has an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, 20.9±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.