# US 11,993,605 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 11,993,605 B2
- Document ID: US11993605B2
- Status: Granted
- Kind: B2
- Application number: 18/176,664
- Filed: 2023-03-01
- Published: 2023-10-05
- Granted: 2024-05-28
- Earliest claimed: 2015-10-16
- Assignees: AbbVie Inc.
- Applicants: AbbVie Inc.
- Inventors: Mohamed-Eslam F. Mohamed; Ahmed A. Othman; Ben Klünder; Aileen L. Pangan; Jaclyn Kay Anderson; Jeffrey W. Voss; Robert J. Padley; Heidi S. Camp
- Web page: https://patentgrep.com/patent/US11993605B2

## CPC

- C07D 487/14: Ortho-condensed systems
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- 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
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- 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 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, ankylosing spondylitis, and psoriatic arthritis), kits, methods of synthesis, and products-by-process.

## Claims

### Claim 1

A method of treating a human patient having active psoriatic arthritis, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount 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 (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 disease-modifying antirheumatic drugs.

### Claim 4 (depends on 1)

The method of claim 1, wherein the patient has had an inadequate response or intolerance to methotrexate.

### Claim 5 (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 6 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.

### Claim 7

A method of treating a human patient having active psoriatic arthritis, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount 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 (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the method results in an ACR70 response at 12 weeks after the first daily administration.

### Claim 8 (depends on 7)

The method of claim 7, wherein the patient is an adult patient.

### Claim 9 (depends on 7)

The method of claim 7, wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

### Claim 10 (depends on 7)

The method of claim 7, wherein the patient has had an inadequate response or intolerance to methotrexate.

### Claim 11 (depends on 7)

The method of claim 7, wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.

### Claim 12 (depends on 7)

The method of claim 7, wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.

### Claim 13

A method of treating a human patient having active psoriatic arthritis, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount 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 (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the method results in an ACR50 response at 12 weeks after the first daily administration.

### Claim 14 (depends on 13)

The method of claim 13, wherein the patient is an adult patient.

### Claim 15 (depends on 13)

The method of claim 13, wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

### Claim 16 (depends on 13)

The method of claim 13, wherein the patient has had an inadequate response or intolerance to methotrexate.

### Claim 17 (depends on 13)

The method of claim 13, wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.

### Claim 18 (depends on 13)

The method of claim 13, wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.

### Claim 19

A method of treating a human patient having active psoriatic arthritis, comprising orally administering once daily to the patient a tablet comprising a therapeutically effective amount 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 (Compound 1), wherein the therapeutically effective amount is 15 mg, and wherein the method results in an ACR20 response at 12 weeks after the first daily administration.

### Claim 20 (depends on 19)

The method of claim 19, wherein the patient is an adult patient.

### Claim 21 (depends on 19)

The method of claim 19, wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

### Claim 22 (depends on 19)

The method of claim 19, wherein the patient has had an inadequate response or intolerance to methotrexate.

### Claim 23 (depends on 19)

The method of claim 19, wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent.

### Claim 24 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of Compound 1 is administered as 15.4 mg of Freebase Hydrate Form C.