# US 12,110,298 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 12,110,298 B2
- Document ID: US12110298B2
- Status: Granted
- Kind: B2
- Application number: 18/369,272
- Filed: 2023-09-18
- Published: 2024-01-11
- Granted: 2024-10-08
- Earliest claimed: 2015-10-16
- Assignees: AbbVie Inc.
- Applicants: AbbVie Inc.
- Inventors: Mathew M. Mulhern; Fredrik Lars Nordstrom; Ahmad Y. Sheikh
- Web page: https://patentgrep.com/patent/US12110298B2

## CPC

- C07D 487/14: Ortho-condensed systems
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 47/02: Inorganic compounds
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 17/14: for baldness or alopecia
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C04B 35/62873: {Carbon}
- C04B 35/62886: {by wet chemical techniques}
- C04B 35/64: Burning or sintering processes (C04B33/32 takes precedence {; powder metallurgy B22F})
- C04B 35/657: for manufacturing refractories (C04B35/05, C04B35/107, C04B35/484 take precedence)
- C04B 35/83: Carbon fibres in a carbon matrix
- C07D 487/04: Ortho-condensed systems
- C04B 2235/422: Carbon
- C04B 2235/48: Organic compounds becoming part of a ceramic after heat treatment, e.g. carbonising phenol resins
- C04B 2235/5248: Carbon, e.g. graphite
- C04B 2235/5256: Two-dimensional, e.g. woven structures
- C04B 2235/616: Liquid infiltration of green bodies or pre-forms
- 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
- C04B: LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE {(roofing granules E04D7/005)}; CERAMICS (devitrified glass-ceramics C03C10/00); REFRACTORIES; TREATMENT OF NATURAL STONE
- 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), kits, methods of synthesis, and products-by-process.

## Claims

### Claim 1

A solid form 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) comprising amorphous freebase or Freebase Hydrate Form C.

### Claim 2 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises between about 0.8% and about 3.7% by weight water.

### Claim 3 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises about 3.7% by weight water.

### Claim 4 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises about 0.8% by weight water.

### Claim 5 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than about 4% by weight water.

### Claim 6 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than about 7% by weight water.

### Claim 7 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than about 10% by weight water.

### Claim 8 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than 12% by weight water.

### Claim 9 (depends on 1)

The solid form of claim 1, wherein the amorphous freebase has glass transition temperature onset at about 119° C.

### Claim 10 (depends on 1)

The solid form of claim 1, wherein the amorphous freebase has glass transition temperature midpoint at about 122° C.

### Claim 11 (depends on 1)

The solid form of claim 1, wherein the solid form is the amorphous freebase, and wherein the amorphous freebase reversibly sorbs up to 13% water at 90% relative humidity at 25° C.

### Claim 12

A process for preparing a pharmaceutical tablet, comprising contacting an amorphous freebase solid form 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) with a pharmaceutically acceptable carrier, wherein the amorphous freebase comprises less than about 13% by weight water.

### Claim 13 (depends on 12)

The process of claim 12, wherein the amorphous freebase comprises less than about 10% by weight water.

### Claim 14 (depends on 13)

The process of claim 13, wherein the amorphous freebase comprises less than about 7% by weight water.

### Claim 15 (depends on 14)

The process of claim 14, wherein the amorphous freebase comprises less than about 4% by weight water.

### Claim 16 (depends on 15)

The process of claim 15, wherein the amorphous freebase comprises about 3.7% by weight water.

### Claim 17 (depends on 15)

The process of claim 15, wherein the amorphous freebase comprises about 0.8% by weight water.

### Claim 18 (depends on 15)

The process of claim 15, wherein the amorphous freebase comprises between about 0.8% and about 3.7% by weight water.

### Claim 19 (depends on 12)

The process of claim 12, wherein the amorphous freebase has a glass transition temperature midpoint at about 119° C.

### Claim 20 (depends on 12)

The process of claim 12, wherein the amorphous freebase has a glass transition temperature midpoint at about 122° C.

### Claim 21 (depends on 12)

The process of claim 12, wherein the amorphous freebase reversibly sorbs up to 13% water at 90% relative humidity at 25° C.

### Claim 22 (depends on 1)

The solid form of claim 1, wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2A.

### Claim 23 (depends on 1)

The solid form of claim 1, wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2B.

### Claim 24 (depends on 2)

The solid form of claim 2, wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2A.

### Claim 25 (depends on 2)

The solid form of claim 2, wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2B.

### Claim 26 (depends on 1)

A pharmaceutical tablet comprising the solid form of claim 1 and a pharmaceutically acceptable carrier.

### Claim 27 (depends on 2)

A pharmaceutical tablet comprising the solid form of claim 2 and a pharmaceutically acceptable carrier.

### Claim 28 (depends on 22)

A pharmaceutical tablet comprising the solid form of claim 22 and a pharmaceutically acceptable carrier.

### Claim 29 (depends on 23)

A pharmaceutical tablet comprising the solid form of claim 23 and a pharmaceutically acceptable carrier.

### Claim 30 (depends on 24)

A pharmaceutical tablet comprising the solid form of claim 24 and a pharmaceutically acceptable carrier.

### Claim 31 (depends on 25)

A pharmaceutical tablet comprising the solid form of claim 25 and a pharmaceutically acceptable carrier.