# US 11,111,264 B2 · Morphic forms of 4-amino-7-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide and uses thereof

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- Number: US 11,111,264 B2
- Document ID: US11111264B2
- Status: Granted
- Kind: B2
- Application number: 16/645,876
- Filed: 2018-09-21
- Published: 2020-09-03
- Granted: 2021-09-07
- Earliest claimed: 2017-09-21
- Assignees: Chimerix, Inc.
- Applicants: Chimerix, Inc.
- Inventors: Roy W. Ware; Venkat Lakshmanan; Aaron Leigh Downey
- Web page: https://patentgrep.com/patent/US11111264B2

## CPC

- C07D 487/04: Ortho-condensed systems
- C07H 19/14: Pyrrolo-pyrimidine radicals
- A61P 31/12: Antivirals
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure relates to crystalline morphic forms of 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl) tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. The morphic form can be a stable hemihydrate crystalline form.

## Claims

### Claim 1

Crystalline 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide hemihydrate.

### Claim 2

A crystalline hemihydrate form (“Form A”) of 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide, wherein said Form has a powder X-ray diffraction pattern comprising a peak at a diffraction angle (20) of about 26.2°, wherein said powder X-ray diffraction pattern is obtained using Cu Kα1 X-rays at a wavelength of 1.5406 Å.

### Claim 3 (depends on 2)

The crystalline hemihydrate of claim 2, wherein the morphic form is further characterized by an endothermic peak at about 231° C. as measured by differential scanning calorimetry.

### Claim 4 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a mass loss of about 2.4% between a temperature of about 110° C. and 220° C. as measured by thermogravimetric analysis.

### Claim 5 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a PXRD pattern substantially similar to that set forth in FIG. 1A.

### Claim 6 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a PXRD pattern substantially similar to that set forth in FIG. 1B.

### Claim 7 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a TG-FTIR profile substantially similar to that set forth in FIG. 8.

### Claim 8 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a DSC profile substantially similar to that set forth in FIG. 15.

### Claim 9 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a DVS profile substantially similar to that set forth in FIG. 20A.

### Claim 10 (depends on 2)

The crystalline hemihydrate form of claim 2, further characterized by a DVS profile substantially similar to that set forth in FIG. 20B.

### Claim 11 (depends on 2)

The crystalline hemihydrate form of claim 2, wherein the morphic form is substantially non-hygroscopic.

### Claim 12

A method of preparing a crystalline hemihydrate form of 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide comprising:
recrystallizing the 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide from a solvent having a water activity of at least about 0.18.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising the crystalline 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide hemihydrate of claim 1, and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 1)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the crystalline 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide hemihydrate of claim 1.

### Claim 15 (depends on 2)

A pharmaceutical composition comprising the crystalline hemihydrate form of claim 2, and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 2)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the crystalline hemihydrate form of claim 2.