[go: up one dir, main page]

WO2014110259A1 - Formes solides d'un inhibiteur de jak - Google Patents

Formes solides d'un inhibiteur de jak Download PDF

Info

Publication number
WO2014110259A1
WO2014110259A1 PCT/US2014/010876 US2014010876W WO2014110259A1 WO 2014110259 A1 WO2014110259 A1 WO 2014110259A1 US 2014010876 W US2014010876 W US 2014010876W WO 2014110259 A1 WO2014110259 A1 WO 2014110259A1
Authority
WO
WIPO (PCT)
Prior art keywords
solid form
degrees
ray powder
powder diffraction
diffraction pattern
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2014/010876
Other languages
English (en)
Inventor
Simon Adam O'NEIL
Yushi Feng
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vertex Pharmaceuticals Inc
Original Assignee
Vertex Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Publication of WO2014110259A1 publication Critical patent/WO2014110259A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the present invention relates to solid state forms of JAK inhibitor (R)-2-(2-(lH- pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2- trifluoroethyl)butanamide, pharmaceutical compositions thereof, and methods therewith.
  • the Janus kinases are a family of tyrosine kinases consisting of JAK1, JAK2, JAK3 and TYK2.
  • the JAKs play a critical role in cytokine signaling.
  • the down-stream substrates of the JAK family of kinases include the signal transducer and activator of transcription (STAT) proteins.
  • STAT signal transducer and activator of transcription
  • JAK/STAT signaling has been implicated in the mediation of many abnormal immune responses such as allergies, asthma, autoimmune diseases such as transplant rejection, rheumatoid arthritis, amyotrophic lateral sclerosis and multiple sclerosis as well as in solid and hematologic malignancies such as leukemias and lymphomas.
  • JAK2 has also been implicated in myeloproliferative disorders, which include polycythemia vera, essential thrombocythemia, chronic idiopathic myelofibrosis, myeloid metaplasia with myelofibrosis, chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic eosinophilic leukemia, hypereosinophilic syndrome and systematic mast cell disease.
  • Compound 1 is useful for treating or reducing the severity of symptoms of one or more JAK mediated diseases (e.g., rheumatoid arthritis, psoriasis, vasculitis, uveitis, myositis, Sjogren's disease, scleroderma lung disease, bronchiolitis, idiopathic pulmonary fibrosis, Guillain-Barre' syndrome (GBS), chronic inflammatory demyelinating polyradiculopathy (CIDP), multifocal motor neuropathy (MMN), Lewis-Sumner syndrome, sarcoidosis, celiac disease, monoclonal gammopathy, amyloidosis, cryoglobulinemia, ulcerative colitis, systemic lupus erythematosis, and the like, or any combination thereof) in a patient.
  • JAK mediated diseases e.g., rheumatoid arthritis, psoriasis, vasculitis, uveit
  • the present invention relates to solid forms of (R)-2-(2-(lH-pyrrolo[2,3-b]pyridin-3- yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide (“Compound 1 ”) having the structure below:
  • compositions thereof are useful for treating or lessening the severity of a variety of JAK mediated diseases.
  • the invention also provides a method of treating or lessening the severity of a JAK-mediated disease (e.g., rheumatoid arthritis (RA), psoriasis, ulcerative colitis (UC), systemic lupus erythematosis (SLE), or the like, or any combination thereof) in a patient comprising administering to the patient one of the compositions (e.g., solid forms) as defined herein.
  • a JAK-mediated disease e.g., rheumatoid arthritis (RA), psoriasis, ulcerative colitis (UC), systemic lupus erythematosis (SLE), or the like, or any combination thereof
  • a JAK-mediated disease e.g., rheumatoid arthritis (RA), psoriasis, ulcerative colitis (UC), systemic lupus erythematosis (SLE), or the like, or any combination thereof
  • the disease is RA or psoriasis.
  • Another aspect of the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a solid form of Compound 1 (as described herein) and a chemotherapy agent (e.g., methotrexate or the like, or any combination thereof).
  • a chemotherapy agent e.g., methotrexate or the like, or any combination thereof.
  • the present invention provides a solid form of a solvate of Compound 1, wherein the solvate comprises Compound 1 and a solvent selected from dimethyl formamide, ethyl acetate, methyl acetate, N-methyl pyrrolidone, tetrahydrofuran (THF), 2-methyl tetrahydrofuran, or 1,4-dioxane.
  • the present invention provides a solid form of a dimethyl formamide solvate of Compound 1 designated as Form XI .
  • solid Form XI is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ⁇ 0.2, 13.3 ⁇ 0.2, 14.1 ⁇ 0.2, 15.4 ⁇ 0.2, 19.3 ⁇ 0.2, and 25.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • solid Form XI is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.6 ⁇ 0.2, 23.4 ⁇ 0.2, and 27.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of an ethyl acetate solvate of Compound 1 designated as Form X2.
  • the solid Form X2 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ⁇ 0.2, 1 1.9 ⁇ 0.2, and 24.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 18.5 ⁇ 0.2 and 28.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a methyl acetate solvate of Compound 1 designated as Form X3.
  • the solid Form X3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ⁇ 0.2, 11.1 ⁇ 0.2, 12.0 ⁇ 0.2, and 24.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X3 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.1 ⁇ 0.2 and 29.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of an N-methyl pyrrolidone solvate of Compound 1 designated as Form X4.
  • the solid Form X4 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.9 ⁇ 0.2, 17.4 ⁇ 0.2, 19.1 ⁇ 0.2, and 24.4 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.9 ⁇ 0.2 and 27.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a
  • the solid Form X5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.9 ⁇ 0.2, 16.1 ⁇ 0.2, 18.7 ⁇ 0.2, 22.3 ⁇ 0.2, and 23.7 ⁇ 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.7 ⁇ 0.2 and 24.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a
  • Form X6 2-methyltetrahydrofuran solvate of Compound 1 designated as Form X6.
  • the solid Form X6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.2 ⁇ 0.2, 15.2 ⁇ 0.2, 22.6 ⁇ 0.2, and 23.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.1 ⁇ 0.2, 11.8 ⁇ 0.2, 16.0 ⁇ 0.2, 17.8 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 20.0 ⁇ 0.2, and 20.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a 1,4-dioxane solvate of Compound 1 designated as Form X7.
  • the solid Form X7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.5 ⁇ 0.2, 15.7 ⁇ 0.2, 21.7 ⁇ 0.2, 22.9 ⁇ 0.2, and 23.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ⁇ 0.2, 11.8 ⁇ 0.2,
  • the present invention provides a solid form of a salt of Compound
  • the salt comprises a hydrochloride, hydrobromide, sulfate, nitrate, mesylate, esylate, besylate, tosylate, naphthalate, naphthalene disulfonate, phosphate, edysilate, or camphor- 10-sulfonate salt of Compound 1.
  • the present invention provides a solid form of a hydrobromide salt of Compound 1 designated as Form X8.
  • the solid Form X8 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the solid Form X8 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.2 ⁇ 0.2, 18.0 ⁇ 0.2, and 30.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9a.
  • the solid Form X9a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.5 ⁇ 0.2, 15.5 ⁇ 0.2, 19.4 ⁇ 0.2, and 23.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X9a is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.6 ⁇ 0.2 and 29.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9b.
  • the solid Form X9b of claim 28 characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ⁇ 0.2, 16.1 ⁇ 0.2, 18.6 ⁇ 0.2, 20.6 ⁇ 0.2, and 28.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X9b of claim 29 further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.1 ⁇ 0.2, 17.9 ⁇ 0.2, 22.1 ⁇ 0.2, 25.6 ⁇ 0.2, and 26.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XI 0a.
  • the solid Form X 10a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ⁇ 0.2, 16.5 ⁇ 0.2, 19.4 ⁇ 0.2, 21.6 ⁇ 0.2, 23.6 ⁇ 0.2, 25.4 ⁇ 0.2, and 27.2 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form XlOa is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XI 0b.
  • the solid Form XI 0b is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.6 ⁇ 0.2, 17.9 ⁇ 0.2, 20.1 ⁇ 0.2, 22.0 ⁇ 0.2, 24.3 ⁇ 0.2, 25.0 ⁇ 0.2, and 27.5 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form XI 0b is further characterized by a peak corresponding to a 2-theta value measured in degrees of 13.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a nitrate salt of Compound 1 designated as Form XI 1.
  • the solid Form XI 1 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the solid Form XI 1 is further characterized by one or more peaks
  • the present invention provides a solid form of a mesylate salt of Compound 1 designated as Form X12.
  • the solid Form X12 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.8 ⁇ 0.2, 20.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21.4 ⁇ 0.2, 22.5 ⁇ 0.2, 23.2 ⁇ 0.2, and 26.7 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form XI 2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the present invention provides a solid form of an esylate salt of Compound 1 designated as Form XI 3.
  • the solid Form XI 3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.3 ⁇ 0.2, 12.6 ⁇ 0.2, 13.8 ⁇ 0.2, 23.7 ⁇ 0.2, 25.2 ⁇ 0.2, and 28.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 3 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a besylate salt of Compound 1 designated as Form X14.
  • the solid Form X14 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.6 ⁇ 0.2, 21.8 ⁇ 0.2, 24.0 ⁇ 0.2, and 29.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.6 ⁇ 0.2, 15.7 ⁇ 0.2, 22.3 ⁇ 0.2,
  • the present invention provides a solid form of a tosylate salt of Compound 1 designated as Form XI 5.
  • the solid Form XI 5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ⁇ 0.2, 12.1 ⁇ 0.2, 15.7 ⁇ 0.2, and 21.9 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a naphthalate salt of Compound 1 designated as Form XI 6.
  • the solid Form XI 6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ⁇ 0.2, 14.0 ⁇ 0.2, 16.6 ⁇ 0.2, 19.1 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, and 26.1 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form XI 6 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the present invention provides a solid form of a naphthalene disulfonate salt of Compound 1 designated as Form XI 7.
  • the solid Form XI 7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ⁇ 0.2, 22.9 ⁇ 0.2, 26.1 ⁇ 0.2, and 27.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.9 ⁇ 0.2, 17.7 ⁇ 0.2, 19.6 ⁇ 0.2, and 24.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a phosphate salt of Compound 1 designated as Form XI 8.
  • the solid Form XI 8 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ⁇ 0.2, 16.1 ⁇ 0.2, 17.5 ⁇ 0.2, 19.8 ⁇ 0.2, 26.0 ⁇ 0.2, and 27.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of an edysilate salt of Compound 1 designated as Form X19.
  • the solid Form X19 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.2 ⁇ 0.2, 23.7 ⁇ 0.2, and 28.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 9 is further characterized by one or more peaks
  • the present invention provides a solid form of a
  • the solid Form X20 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.4 ⁇ 0.2, 17.0 ⁇ 0.2, 17.8 ⁇ 0.2, 23.5 ⁇ 0.2, 24.9 ⁇ 0.2, and
  • the solid Form X20 of claim 63 further characterized by a peak corresponding to a 2-theta value measured in degrees of 16.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising Compound 1 and an acid selected from malonic acid, succinic acid, glutaric acid, fumaric acid, maleic acid, acetylsalicylic acid, 2-oxoglutaric acid, oxalic acid, or glycolic acid.
  • the present invention provides a solid form of a co-crystal comprising malonic acid and Compound 1 designated as Form X21.
  • the solid Form X21 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ⁇ 0.2, 14.7 ⁇ 0.2, 16.1 ⁇ 0.2, 18.2 ⁇ 0.2, 25.0 ⁇ 0.2, 25.7 ⁇ 0.2, and 26.4 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X21 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.0 ⁇ 0.2 and 19.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising succinic acid and Compound 1 designated as Form X22.
  • the solid Form X22 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ⁇ 0.2, 11.3 ⁇ 0.2, 15.4 ⁇ 0.2, 17.2 ⁇ 0.2, 19.2 ⁇ 0.2, and 23.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X22 of claim 69 further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.7 ⁇ 0.2, 13.9 ⁇ 0.2, and 18.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising glutaric acid and Compound 1 designated as Form X23.
  • the solid Form X23 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.3 ⁇ 0.2, 19.0 ⁇ 0.2, 24.1 ⁇ 0.2, and 26.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X23 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.6 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising fumaric acid and Compound 1 designated as Form X24.
  • the solid Form X24 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 5.5 ⁇ 0.2, 8.5 ⁇ 0.2, 14.1 ⁇ 0.2, 19.4 ⁇ 0.2, 21.1 ⁇ 0.2, 23.8 ⁇ 0.2, and 26.6 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X24 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 12.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X25.
  • the solid Form X25 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 3.9 ⁇ 0.2, 5.3 ⁇ 0.2, 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, and 28.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X25 is further
  • the present invention provides a solid form of a co-crystal comprising malic acid and Compound 1 designated as Form X26.
  • the solid Form X26 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.1 ⁇ 0.2, 19.5 ⁇ 0.2, 21.6 ⁇ 0.2, 23.8 ⁇ 0.2, and 26.0 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form X25 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 15.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising acetylsalicylic acid and Compound 1 designated as Form X27.
  • the solid Form X27 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.0 ⁇ 0.2, 19.9 ⁇ 0.2, and 24.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X27 is further
  • the present invention provides a solid form of a co-crystal comprising 2-oxoglutaric acid and Compound 1 designated as Form X28.
  • the solid Form X28 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ⁇ 0.2, 15.8 ⁇ 0.2, 17.1 ⁇ 0.2, 18.2 ⁇ 0.2, and
  • the solid Form X28 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.9 ⁇ 0.2 and 20.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the present invention provides a solid form of a co-crystal comprising oxalic acid and Compound 1 designated as Form X29.
  • the solid Form X29 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ⁇ 0.2, 15.8 ⁇ 0.2, 17.1 ⁇ 0.2, 18.2 ⁇ 0.2, and 23.6 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form X29 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the present invention provides a solid form of a co-crystal comprising glycolic acid and Compound 1 designated as Form X30.
  • the solid Form X30 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ⁇ 0.2, 15.6 ⁇ 0.2, and 23.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X30 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.5 ⁇ 0.2, 18.4 ⁇ 0.2,
  • the present invention provides an amorphous form of
  • Figure 1 is an exemplary X-Ray powder diffraction pattern of Form XI .
  • Figure 2 is an exemplary X-Ray powder diffraction pattern of Form X2.
  • Figure 3 is an exemplary X-Ray powder diffraction pattern of Form X3.
  • Figure 4 is an exemplary X-Ray powder diffraction pattern of Form X4.
  • Figure 5 is an exemplary X-Ray powder diffraction pattern of Form X5.
  • Figure 6 is an exemplary X-Ray powder diffraction pattern of Form X6.
  • Figure 7 is an exemplary X-Ray powder diffraction pattern of Form X7.
  • Figure 8 is an exemplary X-Ray powder diffraction pattern of Form X8.
  • Figure 9 is an exemplary X-Ray powder diffraction pattern of Form X9a.
  • Figure 10 is an exemplary X-Ray powder diffraction pattern of Form X9b.
  • Figure 1 1 is an exemplary X-Ray powder diffraction pattern of Form XlOa.
  • Figure 12 is an exemplary X-Ray powder diffraction pattern of Form XI 0b.
  • Figure 13 is an exemplary X-Ray powder diffraction pattern of Form XI 1.
  • Figure 14 is an exemplary X-Ray powder diffraction pattern of Form XI 2.
  • Figure 15 is an exemplary X-Ray powder diffraction pattern of Form XI 3.
  • Figure 16 is an exemplary X-Ray powder diffraction pattern of Form X14.
  • Figure 17 is an exemplary X-Ray powder diffraction pattern of Form XI 5.
  • Figure 18 is an exemplary X-Ray powder diffraction pattern of Form XI 6.
  • Figure 19 is an exemplary X-Ray powder diffraction pattern of Form XI 7.
  • Figure 20 is an exemplary X-Ray powder diffraction pattern of Form XI 8.
  • Figure 21 is an exemplary X-Ray powder diffraction pattern of Form X19.
  • Figure 22 is an exemplary X-Ray powder diffraction pattern of Form X20.
  • Figure 23 is an exemplary X-Ray powder diffraction pattern of Form X21.
  • Figure 24 is an exemplary X-Ray powder diffraction pattern of Form X22.
  • Figure 25 is an exemplary X-Ray powder diffraction pattern of Form X23.
  • Figure 26 is an exemplary X-Ray powder diffraction pattern of Form X24.
  • Figure 27 is an exemplary X-Ray powder diffraction pattern of Form X25.
  • Figure 28 is an exemplary X-Ray powder diffraction pattern of Form X26.
  • Figure 29 is an exemplary X-Ray powder diffraction pattern of Form X27.
  • Figure 30 is an exemplary X-Ray powder diffraction pattern of Form X28.
  • Figure 31 is an exemplary X-Ray powder diffraction pattern of Form X29.
  • Figure 32 is an exemplary X-Ray powder diffraction pattern of Form X30.
  • Figure 33 is an exemplary X-Ray powder diffraction pattern of Form X31. DETAILED DESCRIPTION
  • the present invention provides solid forms of Compound 1 , methods of preparing solid forms of Compound 1, and methods of treating JAK-mediated diseases (e.g., RA, psoriasis, UC, SLE, or the like, or any combination thereof) using a solid form of Compound 1.
  • JAK-mediated diseases e.g., RA, psoriasis, UC, SLE, or the like, or any combination thereof
  • Compound 1 is (R)-2-(2-(lH-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin- 4-ylamino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide (“Compound 1") having the structure below:
  • solid form refers to a compound or composition (e.g., salts, solvates, or co-crystals of compounds) in a solid physical state.
  • Solid forms includes crystalline, semi-crystalline, and amorphous compounds and compositions.
  • Crystalline solid forms of compounds or compositions possess structural units that are arranged in fixed geometric patterns or lattices, so that crystalline solids have rigid long range order.
  • the structural units that constitute the crystal structure can be atoms, molecules, or ions.
  • Crystalline solids may possess physical properties that may include a definite melting point.
  • an “ion” refers to an atom or polyatomic species wherein the total number of electrons is not equal to the total number of protons, giving the atom a net positive or negative electrical charge.
  • salt refers to an ionic compound that results from the
  • Salts are composed of cations (positively charged ions) and anions (negative ions) so that the product is electrically neutral (without a net charge).
  • a "co-crystal” consists of two or more components that form a unique crystalline structure having unique properties.
  • a co-crystal comprises a crystalline structure composed of at least two components, where the components may be atoms, ions or molecules.
  • the components of the co-crystal are solid in their pure forms at ambient conditions.
  • a "solvate" refers to a crystal form of a compound with either stoichiometric or non-stoichiometric amount of solvent.
  • X-ray powder diffraction and “XRPD” are used interchangeable.
  • Method 1 XRPD patterns were acquired at room temperature in reflection mode using a Bruker D8 Discover diffractometer equipped with a sealed tube Cu source and a Hi- Star area detector (Bruker AXS, Madison, WI). The X-Ray generator was operating at a voltage of 40 kV and a current of 35 mA. The powder sample was placed in a nickel holder. Two frames were registered with an exposure time of 120 s each. The data frames were subsequently integrated over the range of 4.5° - 22.4° and 21.0° - 39.0° 2q merged into one continuous pattern.
  • Method 2 XRPD patterns were recorded at room temperature in reflection mode using a Bruker D8 Advance diffractometer equipped with a sealed tube Cu source and a Vantec PSD detector (Bruker AXS, Madison, WI). The X-ray generator was operating at a voltage of 40 kV and a current of 40 mA. The powder sample was placed in a silicon or PMM holder. The data were recorded in a q-q scanning mode over the range of 4°-45° 2q with a step size of 0.014° and a dwell time of Is per step.
  • One aspect the present invention provides a solid form of a solvate of Compound 1, wherein the solvate comprises Compound 1 and a solvent selected from dimethyl formamide, ethyl acetate, methyl acetate, N-methyl pyrrolidone, tetrahydrofuran (THF), 2-methyl tetrahydrofuran, or 1,4-dioxane.
  • a solvent selected from dimethyl formamide, ethyl acetate, methyl acetate, N-methyl pyrrolidone, tetrahydrofuran (THF), 2-methyl tetrahydrofuran, or 1,4-dioxane.
  • the present invention provides a solid form of a dimethyl formamide solvate of Compound 1 designated as Form XI .
  • solid form of a dimethyl formamide solvate of Compound 1 designated as Form XI .
  • Form XI is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ⁇ 0.2, 13.3 ⁇ 0.2, 14.1 ⁇ 0.2, 15.4 ⁇ 0.2, 19.3 ⁇ 0.2, and 25.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • solid Form XI is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.6 ⁇ 0.2,
  • Form XI is characterized by an XRPD
  • Table 1 XRPD pattern for Form XI .
  • the present invention provides a solid form of an ethyl acetate solvate of Compound 1 designated as Form X2.
  • the solid Form X2 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ⁇ 0.2, 11.9 ⁇ 0.2, and 24.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 18.5 ⁇ 0.2 and 28.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X2 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 2 XRPD pattern for Form X2.
  • the present invention provides a solid form of a methyl acetate solvate of Compound 1 designated as Form X3.
  • the solid Form X3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ⁇ 0.2, 1 1.1 ⁇ 0.2, 12.0 ⁇ 0.2, and 24.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X3 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.1 ⁇ 0.2 and 29.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X3 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 3 XRPD pattern for Form X3.
  • N-methyl pyrrolidone Solvate of Compound 1 provides a solid form of an N-methyl pyrrolidone solvate of Compound 1 designated as Form X4.
  • the solid Form X4 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.9 ⁇ 0.2, 17.4 ⁇ 0.2, 19.1 ⁇ 0.2, and 24.4 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.9 ⁇ 0.2 and 27.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X4 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 4 XRPD pattern for Form X4.
  • the present invention provides a solid form of a
  • the solid Form X5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.9 ⁇ 0.2, 16.1 ⁇ 0.2, 18.7 ⁇ 0.2, 22.3 ⁇ 0.2, and 23.7 ⁇ 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • Form X5 is characterized by an XRPD
  • Table 5 XRPD pattern for Form X5.
  • the present invention provides a solid form of a
  • Form X6 2-methyltetrahydrofuran solvate of Compound 1 designated as Form X6.
  • the solid Form X6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.2 ⁇ 0.2, 15.2 ⁇ 0.2, 22.6 ⁇ 0.2, and 23.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.1 ⁇ 0.2, 11.8 ⁇ 0.2, 16.0 ⁇ 0.2, 17.8 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 20.0 ⁇ 0.2, and 20.7 ⁇ 0.2, in an X-ray powder diffraction pattern.
  • Form X6 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 6 XRPD pattern for Form X6.
  • the present invention provides a solid form of a 1,4-dioxane solvate of Compound 1 designated as Form X7.
  • the solid Form X7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of
  • the solid Form X7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ⁇ 0.2, 1 1.8 ⁇ 0.2,
  • Form X7 is characterized by an XRPD
  • the present invention provides a salt of Compound 1.
  • the salt of Compound 1 comprises a solid form of a salt of Compound 1 , wherein the salt comprises a hydrochloride, hydrobromide, sulfate, nitrate, mesylate, esylate, besylate, tosylate, naphthalate, naphthalene disulfonate, phosphate, edysilate, or
  • the present invention provides a hydrobromide salt of
  • Compound 1 Compound 1 ⁇ HBr.
  • the present invention provides a solid form of a hydrobromide salt of Compound 1 designated as Form X8.
  • the solid Form X8 is characterized by one or more peaks corresponding to
  • the solid Form X8 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.2 ⁇ 0.2, 18.0 ⁇ 0.2, and 30.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X8 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 8 XRPD pattern for Form X8.
  • the present invention provides a hydrochloride salt of Compound 1 : Compound 1 ⁇ HC1.
  • the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9a.
  • the solid Form X9a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.5 ⁇ 0.2, 15.5 ⁇ 0.2, 19.4 ⁇ 0.2, and 23.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X9a is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.6 ⁇ 0.2 and 29.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X9a is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 9 XRPD pattern for Form X9a.
  • the present invention provides a hydrochloride salt of Compound 1 : Compound 1 ⁇ HC1.
  • the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9b.
  • the solid Form X9b of claim 28 characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ⁇ 0.2, 16.1 ⁇ 0.2, 18.6 ⁇ 0.2, 20.6 ⁇ 0.2, and 28.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X9b of claim 29, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.1 ⁇ 0.2, 17.9 ⁇ 0.2, 22.1 ⁇ 0.2, 25.6 ⁇ 0.2, and 26.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X9b is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 10 XRPD pattern for Form X9b.
  • the present invention provides a sulfate salt of Compound 1 : Compound 1 ⁇ H 2 S0 4 .
  • the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XlOa.
  • the solid Form X 10a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ⁇ 0.2, 16.5 ⁇ 0.2, 19.4 ⁇ 0.2, 21.6 ⁇ 0.2, 23.6 ⁇ 0.2, 25.4 ⁇ 0.2, and 27.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 0a is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.8 ⁇ 0.2 and 24.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form XI 0a is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 11 XRPD pattern for Form XI 0a.
  • the present invention provides a sulfate salt of Compound 1 : Compound 1 ⁇ H 2 S0 4 .
  • the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XI Ob.
  • the solid Form XI Ob is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.6 ⁇ 0.2, 17.9 ⁇ 0.2, 20.1 ⁇ 0.2, 22.0 ⁇ 0.2, 24.3 ⁇ 0.2, 25.0 ⁇ 0.2, and 27.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 0b is further characterized by a peak corresponding to a 2-theta value measured in degrees of 13.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form XI 0b is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 12 XRPD pattern for Form XlOb.
  • the present invention provides a nitrate salt of Compound 1 : Compound 1 ⁇ HNO3.
  • the present invention provides a solid form of a nitrate salt of Compound 1 designated as Form XI 1.
  • the solid Form XI 1 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.9 ⁇ 0.2, 25.4 ⁇ 0.2, and 33.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 1 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.5 ⁇ 0.2, 13.2 ⁇ 0.2, 14.7 ⁇ 0.2, 15.6 ⁇ 0.2, 19.0 ⁇ 0.2, 22.5 ⁇ 0.2, and 23.9 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form XI 1 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 13 XRPD pattern for Form X 1 1.
  • the present invention provides a mesylate salt of Compound 1 : Compound 1 ⁇ CH3SO3H.
  • the present invention provides a solid form of a mesylate salt of Compound 1 designated as Form XI 2.
  • the solid Form XI 2 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.8 ⁇ 0.2, 20.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21.4 ⁇ 0.2, 22.5 ⁇ 0.2, 23.2 ⁇ 0.2, and 26.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.5 ⁇ 0.2, and 18.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X12 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 14 XRPD pattern for Form X12.
  • the present invention provides an esylate salt of Compound 1 : Compound 1 ⁇ CH3CH2SO3H.
  • the present invention provides a solid form of an esylate salt of Compound 1 designated as Form XI 3.
  • the solid Form XI 3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.3 ⁇ 0.2, 12.6 ⁇ 0.2, 13.8 ⁇ 0.2, 23.7 ⁇ 0.2, 25.2 ⁇ 0.2, and 28.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 3 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form XI 3 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 15 XRPD pattern for Form X13.
  • the present invention provides a besylate salt of Compound 1 : Compound 1 ⁇ benzenesulfonic acid.
  • the present invention provides a solid form of a besylate salt of Compound 1 designated as Form XI 4.
  • the solid Form XI 4 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.6 ⁇ 0.2, 21.8 ⁇ 0.2, 24.0 ⁇ 0.2, and 29.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.6 ⁇ 0.2, 15.7 ⁇ 0.2, 22.3 ⁇ 0.2, 24.9 ⁇ 0.2, and 30.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X14 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 16 XRPD pattern for Form X14.
  • the present invention provides a tosylate salt of Compound 1 : Compound 1 ⁇ p-toluenesulfonic acid. In some embodiments, the present invention provides a solid form of a tosylate salt of Compound 1 designated as Form XI 5. In some
  • the solid Form XI 5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ⁇ 0.2, 12.1 ⁇ 0.2, 15.7 ⁇ 0.2, and 21.9 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form XI 5 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 17 XRPD pattern for Form XI 5.
  • the present invention provides a naphthalate salt of Compound 1 : Compound 1 ⁇ naphthalic acid.
  • the present invention provides a solid form of a naphthalate salt of Compound 1 designated as Form XI 6.
  • the solid Form XI 6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ⁇ 0.2, 14.0 ⁇ 0.2, 16.6 ⁇ 0.2, 19.1 ⁇ 0.2,
  • the solid Form XI 6 is further characterized by one or more peaks
  • Form XI 6 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 18 XRPD pattern for Form XI 6.
  • the present invention provides a naphthalene disulfonate salt of Compound 1 : Compound 1 ⁇ naphthalene- 1,2-disulfonic acid.
  • the present invention provides a solid form of a naphthalene disulfonate salt of Compound 1 designated as Form XI 7.
  • the solid Form XI 7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ⁇ 0.2, 22.9 ⁇ 0.2, 26.1 ⁇ 0.2, and 27.2 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.9 ⁇ 0.2, 17.7 ⁇ 0.2, 19.6 ⁇ 0.2, and 24.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form XI 7 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 19 XRPD pattern for Form XI 7.
  • the present invention provides a phosphate salt of Compound 1 : Compound 1 ⁇ phosphoric acid. In some embodiments, the present invention provides a solid form of a phosphate salt of Compound 1 designated as Form XI 8. In some
  • the solid Form XI 8 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ⁇ 0.2, 16.1 ⁇ 0.2, 17.5 ⁇ 0.2, 19.8 ⁇ 0.2,
  • Form XI 8 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks: Table 20: XRPD pattern for Form XI 8.
  • the present invention provides an edisilate salt of Compound 1 : Compound 1 ⁇ ethane- 1 ,2-disulfonic acid.
  • the present invention provides a solid form of an edysilate salt of Compound 1 designated as Form XI 9.
  • the solid Form XI 9 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.2 ⁇ 0.2, 23.7 ⁇ 0.2, and 28.1 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form XI 9 is further
  • Form X19 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 21 XRPD pattern for Form XI 9.
  • the present invention provides a camphor- 10-sulfonate salt of Compound 1 : Compound 1 ⁇ camphor- 10-sulfonic acid.
  • the present invention provides a solid form of a camphor- 10-sulfonate salt of Compound 1 designated as Form X20.
  • the solid Form X20 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.4 ⁇ 0.2, 17.0 ⁇ 0.2, 17.8 ⁇ 0.2, 23.5 ⁇ 0.2, 24.9 ⁇ 0.2, and 27.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X20 of claim 63 further characterized by a peak corresponding to a 2-theta value measured in degrees of 16.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X20 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 22 XRPD pattern for Form X20.
  • the present invention provides a solid form of a co-crystal comprising Compound 1 and malonic acid, succinic acid, glutaric acid, fumaric acid, maleic acid, or 2-oxoglutaric acid.
  • the present invention provides a solid form of a co-crystal comprising malonic acid and Compound 1 designated as Form X21.
  • the solid Form X21 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ⁇ 0.2, 14.7 ⁇ 0.2, 16.1 ⁇ 0.2, 18.2 ⁇ 0.2, 25.0 ⁇ 0.2, 25.7 ⁇ 0.2, and 26.4 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X21 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ⁇ 0.2, 14.7 ⁇ 0.2, 16.1 ⁇ 0.2, 18.2 ⁇ 0.2, 25.0 ⁇ 0.2, 25.7 ⁇ 0.2, and 26.4 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X21 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ⁇ 0.2, 14.7 ⁇
  • X21 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.0 ⁇ 0.2 and 19.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X21 is characterized by an XRPD
  • Table 23 XRPD pattern for Form X21.
  • the present invention provides a solid form of a co-crystal comprising succinic acid and Compound 1 designated as Form X22.
  • the solid Form X22 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ⁇ 0.2, 11.3 ⁇ 0.2, 15.4 ⁇ 0.2, 17.2 ⁇ 0.2, 19.2 ⁇ 0.2, and 23.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X22 of claim 69 further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.7 ⁇ 0.2, 13.9 ⁇ 0.2, and 18.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X22 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 24 XRPD pattern for Form X22.
  • the present invention provides a solid form of a co-crystal comprising glutaric acid and Compound 1 designated as Form X23.
  • the solid Form X23 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.3 ⁇ 0.2, 19.0 ⁇ 0.2, 24.1 ⁇ 0.2, and 26.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X23 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.6 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X23 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks: Table 25: XRPD pattern for Form X23.
  • the present invention provides a solid form of a co-crystal comprising fumaric acid and Compound 1 designated as Form X24.
  • the solid Form X24 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 5.5 ⁇ 0.2, 8.5 ⁇ 0.2, 14.1 ⁇ 0.2, 19.4 ⁇ 0.2, 21.1 ⁇ 0.2, 23.8 ⁇ 0.2, and 26.6 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X24 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 12.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X24 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 26 XRPD pattern for Form X24.
  • the present invention provides a solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X25.
  • the solid Form X25 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 3.9 ⁇ 0.2, 5.3 ⁇ 0.2, 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, and 28.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X25 is further
  • Form X25 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 27 XRPD pattern for Form X25.
  • the present invention provides a solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X26.
  • the solid Form X26 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.1 ⁇ 0.2, 19.5 ⁇ 0.2, 21.6 ⁇ 0.2, 23.8 ⁇ 0.2, and 26.0 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form X26 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 15.5 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X26 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 28 XRPD pattern for Form X26.
  • the present invention provides a solid form of a co-crystal comprising acetylsalicylic acid and Compound 1 designated as Form X27.
  • the solid Form X27 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ⁇ 0.2, 19.9 ⁇ 0.2, and 24.7 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X27 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ⁇ 0.2, 15.1 ⁇ 0.2, and 28.0 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X27 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:
  • Table 29 XRPD pattern for Form X27.
  • the present invention provides a solid form of a co-crystal comprising 2-oxoglutaric acid and Compound 1 designated as Form X28.
  • the solid Form X28 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 12.9 ⁇ 0.2, 22.6 ⁇ 0.2, 24.7 ⁇ 0.2, and 25.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X28 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.9 ⁇ 0.2 and 20.3 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X28 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 30 XRPD pattern for Form X28.
  • the present invention provides a solid form of a co-crystal comprising oxalic acid and Compound 1 designated as Form X29.
  • the solid Form X29 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ⁇ 0.2, 15.8 ⁇ 0.2, 17.1 ⁇ 0.2, 18.2 ⁇ 0.2, and 23.6 ⁇ 0.2 in an X- ray powder diffraction pattern.
  • the solid Form X29 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.7 ⁇ 0.2, 25.4 ⁇ 0.2, and 26.6 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • Form X29 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:
  • Table 31 XRPD pattern for Form X29.
  • the present invention provides a solid form of a co-crystal comprising glycolic acid and Compound 1 designated as Form X30.
  • the solid Form X30 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ⁇ 0.2, 15.6 ⁇ 0.2, and 23.8 ⁇ 0.2 in an X-ray powder diffraction pattern.
  • the solid Form X30 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.5 ⁇ 0.2, 18.4 ⁇ 0.2,
  • Form X30 is characterized by an XRPD
  • Table 32 XRPD pattern for Form X30.
  • Example 1 Solvates of Compound 1.
  • Solvates of Compound 1, described in section B were generated by suspending 500 mg of Compound 1 in 0.5 to 2 ml of the relevant solvent overnight, i.e., from 12 to 72 hrs. The solvent was evaporated to dryness to generate the resulting solvates of Compound 1 . identified as solid forms XI -X7. The dried solvates were tested without further purification.
  • Example 2 Salts of Compound 1.
  • Salts of Compound 1, as described in section C, were generated at a scale of 250 mg by mixing Compound 1 and the salt coformer as described by Table 31.
  • Example 3 Co-crystals of Compound 1.
  • Example 4 Form X31
  • Amorphous Compound 1 was generated by spray drying a mixture of Compound 1 in a 1 :2 methanol: dichloromethane solution using a Buchi Mini Spray Dryer B-290.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des formes à l'état solide d'un inhibiteur de JAK de (R)-2-(2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-méthyl-N-(2,2,2-trifluoroéthyl)butanamide (composé 1) comprenant des solvates, des sels, des co-cristaux et une forme amorphe de celui-ci. La présente invention concerne également des compositions pharmaceutiques comprenant ces formes solides du composé 1 et des procédés de traitement d'une maladie à médiation par JAK avec ceux-ci.
PCT/US2014/010876 2013-01-09 2014-01-09 Formes solides d'un inhibiteur de jak Ceased WO2014110259A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361750433P 2013-01-09 2013-01-09
US61/750,433 2013-01-09

Publications (1)

Publication Number Publication Date
WO2014110259A1 true WO2014110259A1 (fr) 2014-07-17

Family

ID=50023877

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2014/010876 Ceased WO2014110259A1 (fr) 2013-01-09 2014-01-09 Formes solides d'un inhibiteur de jak

Country Status (1)

Country Link
WO (1) WO2014110259A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018515527A (ja) * 2015-05-13 2018-06-14 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ インフルエンザウイルスの複製の阻害剤
WO2019132654A1 (fr) * 2017-12-27 2019-07-04 Erasmus University Medical Center Rotterdam Méthodes de traitement de la sarcoïdose
WO2020009566A1 (fr) * 2018-07-04 2020-01-09 Erasmus University Medical Center Rotterdam Méthodes de traitement de la sarcoïdose

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005095400A1 (fr) 2004-03-30 2005-10-13 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases et d'autres proteines kinases
WO2007084557A2 (fr) 2006-01-17 2007-07-26 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005095400A1 (fr) 2004-03-30 2005-10-13 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases et d'autres proteines kinases
WO2007084557A2 (fr) 2006-01-17 2007-07-26 Vertex Pharmaceuticals Incorporated Azaindoles utiles comme inhibiteurs de janus kinases

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BRITTAIN H G ED - BRITTAIN H G: "Methods for the Characterization of Polymorphs and Solvates", POLYMORPHISM IN PHARMACEUTICAL SOLIDS, 1999, pages - 278, XP008098996, ISBN: 978-0-8247-0237-9 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018515527A (ja) * 2015-05-13 2018-06-14 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ インフルエンザウイルスの複製の阻害剤
US10273233B2 (en) 2015-05-13 2019-04-30 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
WO2019132654A1 (fr) * 2017-12-27 2019-07-04 Erasmus University Medical Center Rotterdam Méthodes de traitement de la sarcoïdose
WO2020009566A1 (fr) * 2018-07-04 2020-01-09 Erasmus University Medical Center Rotterdam Méthodes de traitement de la sarcoïdose

Similar Documents

Publication Publication Date Title
JP6162904B2 (ja) 新規複素環式化合物
AU2018236703A1 (en) Pyrimidine derivatives for the treatment of viral infections
TWI649314B (zh) 吲唑之合成
KR102774784B1 (ko) Jak를 억제하기 위한 화합물 및 방법
EP2970304B1 (fr) Modulateurs de p2x7
IL263306A (en) Pyrazolopyrimidine derivatives as kinase inhibitors
ES2989149T3 (es) Inhibidores de HAT p300/CBP
CN103889987A (zh) 作为btk-抑制剂的4-咪唑并哒嗪-1-基-苯甲酰胺类和4-咪唑并三嗪-1-基-苯甲酰胺类
ES2714048T3 (es) Moduladores de P2X7
TWI851747B (zh) 介導酪氨酸激酶2活性的雜環化合物
WO2014110259A1 (fr) Formes solides d'un inhibiteur de jak
EP3752250B1 (fr) Inhibiteurs de hat p300/cbp
KR102220848B1 (ko) 화합물 (s)-3-｛4-[5-(2-시클로펜틸-6-메톡시-피리딘-4-일)-[1,2,4]옥사디아졸-3-일]-2-에틸-6-메틸-페녹시｝-프로판-1,2-디올의 결정형
EP4249469A2 (fr) Nouveaux procédés et intermédiaires pour la préparation de stimulateurs de la guanylate cyclase soluble
CZ2014773A3 (cs) Soli (3R)-3-cyklopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propannitrilu
AU2019339994B2 (en) Furo[3,4-b]pyrrole-containing BTK inhibitor
CN108699082B (zh) 具有jak抑制作用的化合物的晶体
WO2015078424A1 (fr) Formes cristallines de vémurafenib
WO2015120393A1 (fr) Triazolobenzodiazépines substituées
WO2022002859A1 (fr) N-phénylacétamides substitués ayant une activité antagoniste du récepteur p2x4
EP3959204A1 (fr) Modulateur du récepteur de la sphingosine-1-phosphate
TWI905843B (zh) 嘧啶胺類nuak抑制劑及其製備方法和用途
TWI902351B (zh) 嘧啶胺類nuak抑制劑及其製備方法和用途
WO2025172882A1 (fr) Dérivés d'acide pyrrolidine-2-carboxylique substitués, utilisés en tant qu'inhibiteurs de cgas
EA037031B1 (ru) Имидазопиразиновые ингибиторы тирозинкиназы брутона

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14701645

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14701645

Country of ref document: EP

Kind code of ref document: A1