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WO2024148164A1 - Solid forms and methods of use - Google Patents

Solid forms and methods of use Download PDF

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Publication number
WO2024148164A1
WO2024148164A1 PCT/US2024/010321 US2024010321W WO2024148164A1 WO 2024148164 A1 WO2024148164 A1 WO 2024148164A1 US 2024010321 W US2024010321 W US 2024010321W WO 2024148164 A1 WO2024148164 A1 WO 2024148164A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
xrpd pattern
certain embodiments
peak
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
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PCT/US2024/010321
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French (fr)
Inventor
Sheila Dewitt
Vincent Jacques
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.)
Salarius Pharmaceuticals Inc
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Salarius Pharmaceuticals Inc
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Filing date
Publication date
Application filed by Salarius Pharmaceuticals Inc filed Critical Salarius Pharmaceuticals Inc
Priority to EP24705274.9A priority Critical patent/EP4646407A1/en
Priority to AU2024206378A priority patent/AU2024206378A1/en
Publication of WO2024148164A1 publication Critical patent/WO2024148164A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • a pharmaceutical composition comprising an anhydrous crystalline form of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient.
  • a pharmaceutical composition comprising the Form I of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient.
  • a pharmaceutical composition comprising the Form II of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient.
  • a pharmaceutical composition comprising the Form III of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient.
  • FIG.1A is an X-ray powder diffraction (XRPD) pattern of Form I of the compound of formula (I) calculated from single crystal X-ray diffraction (XRD) data, as further described in Example 2.
  • FIG.1B is an overlay of an XRPD pattern of Form I of the compound of formula (I) calculated from single crystal XRD data and an exemplary experimental XRPD pattern of Form I of a compound of formula (I).
  • FIG.5 is an XRPD pattern of Form V of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2.
  • FIG.6 is an XRPD pattern of Form VI of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2.
  • FIG.7 is an XRPD pattern of Form VII of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2.
  • FIG.8 is an XRPD pattern of Form VIII of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2.
  • FIG.21 is an exemplary water sorption isotherm recorded at 25°C for Form I of the compound of formula (I).
  • FIG.22 is an overlay of DSC and TGA thermograms for Form X of the compound of formula (I).
  • FIG.23 is an exemplary water sorption isotherm recorded at 25°C for Form X of the compound of formula (I).
  • Attorney Docket No. SLU-030WO [037]
  • FIG.24 is an exemplary XRPD pattern of the crystalline material prepared as described in Example 1 showing a mixture of Forms I and II of the compound of formula (I).
  • FIG.25 is an exemplary DSC thermogram for the crystalline material of the compound of formula (I) prepared as described in Example 1.
  • the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ⁇ 0.3° 2 ⁇ . In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ⁇ 0.3° 2 ⁇ . In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ⁇ 0.3°, 11.9° ⁇ 0.3°, and 14.1° ⁇ 0.3° 2 ⁇ .
  • the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1A. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.2. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.4. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.5.
  • the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ⁇ 0.2° 2 ⁇ .
  • Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 10.3° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 13.7° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 17.6° ⁇ 0.2°, 18.7° ⁇ 0.2°, 19.7° ⁇ 0.2°, 21.6° ⁇ 0.2°, 23.0° ⁇ 0.2°, 23.7° ⁇ 0.2°, and 24.6° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 26.1° ⁇ 0.2°, 26.4° ⁇ 0.2°, 26.8° ⁇ 0.2°, 28.2° ⁇ 0.2°, 30.3° ⁇ 0.2°, 30.5° ⁇ 0.2°, and 33.0° ⁇ 0.2° 2 ⁇ .
  • Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 10.3° ⁇ 0.2°, 11.0° ⁇ 0.2°, 11.9° ⁇ 0.2°, 13.7° ⁇ 0.2°, 14.0° ⁇ 0.2°, 14.8° ⁇ 0.2°, 15.3° ⁇ 0.2°, 17.4° ⁇ 0.2°, 17.6° ⁇ 0.2°, 18.7° ⁇ 0.2°, 19.7° ⁇ 0.2°, 20.6° ⁇ 0.2°, 21.1° ⁇ 0.2°, 21.6° ⁇ 0.2°, 23.0° ⁇ 0.2°, 23.2° ⁇ 0.2°, 23.7° ⁇ 0.2°, 24.1° ⁇ 0.2°, 24.6° ⁇ 0.2°, 25.6° ⁇ 0.2°, 26.1° ⁇ 0.2°, 26.4° ⁇ 0.2°, 26.8° ⁇ 0.2°, 27.1° ⁇ 0.2°, 28.2° ⁇
  • Form I of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1A.
  • Form I of the compound of formula (I) exists in an orthorhombic crystal system.
  • Form I of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group.
  • Form I of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 1.
  • Form I of the compound of formula (I) has a differential scanning calorimetry (DSC) thermogram comprising an endotherm with a peak onset at about 238 °C. In certain embodiments, Form I of the compound of formula (I) has a DSC thermogram comprising an endotherm with a peak onset at about 273.9 °C. In certain embodiments, Form I of the compound of formula (I) has a DSC thermogram comprising one or more endotherms with peak onsets at about 238 °C and about 273.9 °C.
  • Form I of the compound of formula (I) has a DSC thermogram substantially the same as shown in FIG.20.
  • Form I of the compound of formula (I) exhibits a change in mass of less than or equal to about 3% wt (weight) when varying the relative humidity between 0% and about 80%, when measured at 25 °C.
  • the mass change exhibited by Form I Attorney Docket No. SLU-030WO of the compound of formula (I) as a function of humidity can be determined, for example, using Dynamic Vapor Sorption (DVS).
  • Form I of the compound of formula (I) has a water sorption isotherm, when measured at 25 °C, substantially the same as shown in FIG.21.
  • the XRPD pattern further comprises one or more peaks selected from about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.8°, about 33.6°, about 33.8°, about 34.3°, and about 34.5° 2 ⁇ .
  • Form III of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, about 14.3°, about 15.1°, about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.0°, about 19.3°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 21.8°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, about 24.7°, about 24.9°, about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.1°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.3°, about 32.5°, about 32.8°, about 33.1°, about 33.6°, about 33.8
  • Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.7° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 12.2° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 15.1° ⁇ 0.3°, 19.0° ⁇ 0.3°, 19.3° ⁇ 0.3°, 21.8° ⁇ 0.3°, and 24.9° ⁇ 0.3° 2 ⁇ .
  • SLU-030WO further comprises one or more peaks selected from 27.7° ⁇ 0.3°, 28.3° ⁇ 0.3°, 28.6° ⁇ 0.3°, 28.8° ⁇ 0.3°, 29.6° ⁇ 0.3°, 30.3° ⁇ 0.3°, 30.6° ⁇ 0.3°, 31.0° ⁇ 0.3°, 31.4° ⁇ 0.3°, 32.8° ⁇ 0.3°, 33.6° ⁇ 0.3°, 33.8° ⁇ 0.3°, 34.3° ⁇ 0.3°, and 34.5° ⁇ 0.3° 2 ⁇ .
  • Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7° ⁇ 0.3°, 10.9° ⁇ 0.3°, 11.9° ⁇ 0.3°, 12.2° ⁇ 0.3°, 13.3° ⁇ 0.3°, 14.3° ⁇ 0.3°, 15.1° ⁇ 0.3°, 16.0° ⁇ 0.3°, 16.2° ⁇ 0.3°, 16.8° ⁇ 0.3°, 18.7° ⁇ 0.3°, 19.0° ⁇ 0.3°, 19.3° ⁇ 0.3°, 19.9° ⁇ 0.3°, 20.2° ⁇ 0.3°, 21.2° ⁇ 0.3°, 21.5° ⁇ 0.3°, 21.8° ⁇ 0.3°, 22.7° ⁇ 0.3°, 23.5° ⁇ 0.3°, 24.0° ⁇ 0.3°, 24.5° ⁇ 0.3°, 24.7° ⁇ 0.3°, 24.9° ⁇ 0.3°, 26.1° ⁇ 0.3°,
  • Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.7° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 12.2° ⁇ 0.2° 2 ⁇ .
  • Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 13.3° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7° ⁇ 0.2°, 10.9° ⁇ 0.2°, 11.9° ⁇ 0.2°, 12.2° ⁇ 0.2°, 13.3° ⁇ 0.2°, and 14.3° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 15.1° ⁇ 0.2°, 19.0° ⁇ 0.2°, 19.3° ⁇ 0.2°, 21.8° ⁇ 0.2°, and 24.9° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 16.0° ⁇ 0.2°, 16.2° ⁇ 0.2°, 16.8° ⁇ 0.2°, 18.7° ⁇ 0.2°, 19.9° ⁇ 0.2°, 20.2° ⁇ 0.2°, 21.2° ⁇ 0.2°, 21.5° ⁇ 0.2°, 22.7° ⁇ 0.2°, 23.5° ⁇ 0.2°, 24.0° ⁇ 0.2°, 24.5° ⁇ 0.2°, and 24.7° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 26.1° ⁇ 0.2°, 26.4° ⁇ 0.2°, 26.7° ⁇ 0.2°, 26.9° ⁇ 0.2°, 29.1° ⁇ 0.2°, 32.3° ⁇ 0.2°, 32.5° ⁇ 0.2°, 33.1° ⁇ 0.2°, and 34.1° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 27.7° ⁇ 0.2°, 28.3° ⁇ 0.2°, 28.6° ⁇ 0.2°, Attorney Docket No.
  • Form III of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2 ⁇ ) disclosed in Table 13. [144] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. [145] In certain embodiments, Form III of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form III of the compound of formula (I) exists in a monoclinic crystal system and has a P121/n1 space group. In certain embodiments, Form III of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 2.
  • Form X of a compound of formula (I) is an anhydrous crystalline form.
  • Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.6° 2 ⁇ .
  • Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 25.8°, about 26.4°, about 28.7°, about 30.6°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2 ⁇ .
  • Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 14.5° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ⁇ 0.3°, 10.9° ⁇ 0.3°, 12.0° ⁇ 0.3°, 14.1° ⁇ 0.3°, and 14.5° ⁇ 0.3° 2 ⁇ . [153] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ⁇ 0.3°, 19.1° ⁇ 0.3°, 21.9° ⁇ 0.3°, and 24.1° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 17.5° ⁇ 0.3°, 18.0° ⁇ 0.3°, 18.8° ⁇ 0.3°, 19.7° ⁇ 0.3°, 20.7° ⁇ 0.3°, 21.2° ⁇ 0.3°, 21.6° ⁇ 0.3°, 22.3° ⁇ 0.3°, 23.3° ⁇ 0.3°, and 24.6° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.2° ⁇ 0.3°, 27.3° ⁇ 0.3°, 29.0° ⁇ 0.3°, 29.2° ⁇ 0.3°, 30.8° ⁇ 0.3°, and 31.1° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.8° ⁇ 0.3°, 26.4° ⁇ 0.3°, 28.7° ⁇ 0.3°, 30.6° ⁇ 0.3°, 32.4° ⁇ 0.3°, 33.0° ⁇ 0.3°, 33.5° ⁇ 0.3°, 33.9° ⁇ 0.3°, and 34.7° ⁇ 0.3° 2 ⁇ .
  • Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ⁇ 0.3°, 10.9° ⁇ 0.3°, 12.0° ⁇ 0.3°, 14.1° ⁇ 0.3°, 14.5° ⁇ 0.3°, 15.3° ⁇ 0.3°, 17.5° ⁇ 0.3°, 18.0° ⁇ 0.3°, 18.8° ⁇ 0.3°, 19.1° ⁇ 0.3°, 19.7° ⁇ 0.3°, 20.7° ⁇ 0.3°, 21.2° ⁇ 0.3°, 21.6° ⁇ 0.3°, 21.9° ⁇ 0.3°, 22.3° ⁇ 0.3°, 23.3° ⁇ 0.3°, 24.1° ⁇ 0.3°, 24.6° ⁇ 0.3°, 25.2° ⁇ 0.3°, 25.8° ⁇ 0.3°, 26.4° ⁇ 0.3°, 27.3° ⁇ 0.3°, 28.7° ⁇ 0.3°, 29.0° ⁇
  • Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 14.5° ⁇ 0.2° 2 ⁇ .
  • Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ⁇ 0.2°, 10.9° ⁇ 0.2°, 12.0° ⁇ 0.2°, 14.1° ⁇ 0.2°, and 14.5° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 15.3° ⁇ 0.2°, 19.1° ⁇ 0.2°, 21.9° ⁇ 0.2°, and 24.1° ⁇ 0.2° 2 ⁇ .
  • Form X of the compound of formula (I) has a DSC thermogram comprising one or more endotherms with peak onsets at about 235.8 °C and about 281.9 °C. In certain embodiments, Form X of the compound of formula (I) has a DSC thermogram substantially the same as shown in FIG.22. Attorney Docket No. SLU-030WO [163] In certain embodiments, Form X of the compound of formula (I) exhibits a change in mass of less than or equal to about 3% wt when varying the relative humidity between 0% and about 80%, when measured at 25 °C.
  • Crystalline Hydrate of a Compound of Formula (I) [165] In one aspect, provided herein are crystalline hydrate forms of a compound of formula (I). In certain embodiments, the crystalline hydrate of the compound of formula (I) is a crystalline monohydrate. (A) Form II [166] In one aspect, provided herein is Form II of a compound of formula (I). [167] In certain embodiments, Form II of the compound of formula (I) is a crystalline hydrate. In certain embodiments, Form II of the compound of formula (I) is a crystalline monohydrate. [168] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 6.9° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, and about 28.8° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 28.6°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2 ⁇ .
  • Form II of the compound of formula (I) has an XRPD pattern comprising peaks at about 6.9°, about 11.2°, about 11.7°, about 13.9°, about 14.3°, about 15.3°, about 15.5°, about 17.4°, about 17.9°, about 19.7°, about 20.9°, about 21.4°, about 22.3°, about 22.8°, about 23.6°, about 23.8°, about 24.9°, about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, about 28.6°, about 28.8°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2 ⁇ .
  • Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9° ⁇ 0.3°, 11.2° ⁇ 0.3°, 11.7° ⁇ 0.3°, 13.9° ⁇ 0.3°, and 14.3° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.2° ⁇ 0.3°, 25.5° ⁇ 0.3°, 25.7° ⁇ 0.3°, 26.4° ⁇ 0.3°, 27.0° ⁇ 0.3°, 27.5° ⁇ 0.3°, Attorney Docket No. SLU-030WO 28.1° ⁇ 0.3°, 28.2° ⁇ 0.3°, and 28.8° ⁇ 0.3° 2 ⁇ .
  • Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9° ⁇ 0.3°, 11.2° ⁇ 0.3°, 11.7° ⁇ 0.3°, 13.9° ⁇ 0.3°, 14.3° ⁇ 0.3°, 15.3° ⁇ 0.3°, 15.5° ⁇ 0.3°, 17.4° ⁇ 0.3°, 17.9° ⁇ 0.3°, 19.7° ⁇ 0.3°, 20.9° ⁇ 0.3°, 21.4° ⁇ 0.3°, 22.3° ⁇ 0.3°, 22.8° ⁇ 0.3°, 23.6° ⁇ 0.3°, 23.8° ⁇ 0.3°, 24.9° ⁇ 0.3°, 25.2° ⁇ 0.3°, 25.5° ⁇ 0.3°, 25.7° ⁇ 0.3°, 26.4° ⁇ 0.3°, 27.0° ⁇ 0.3°, 27.5° ⁇ 0.3°, 28.1° ⁇ 0.3°, 28.2° ⁇ 0.3°
  • Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 6.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 11.2° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 11.7° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.2° ⁇ 0.2°, 25.5° ⁇ 0.2°, 25.7° ⁇ 0.2°, 26.4° ⁇ 0.2°, 27.0° ⁇ 0.2°, 27.5° ⁇ 0.2°, 28.1° ⁇ 0.2°, 28.2° ⁇ 0.2°, and 28.8° ⁇ 0.2° 2 ⁇ .
  • Form II of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2 ⁇ ) disclosed in Table 12. [181] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.2. [182] In certain embodiments, Form II of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form II of the compound of formula (I) exists in an orthorhombic crystal system and has a C2221 space group. In certain embodiments, Form II of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 3.
  • the crystalline solvate of the compound of formula (I) is a methanol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an ethylene glycol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetone solvate.
  • the crystalline solvate of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, the crystalline solvate of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group.
  • (A) Form IV [186] In one aspect, provided herein is Form IV of a compound of formula (I). [187] In certain embodiments, Form IV of the compound of formula (I) is a crystalline acetonitrile solvate. In certain embodiments, Form IV of the compound of formula (I) is a crystalline mono-acetonitrile solvate.
  • Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 7.6°, about 8.0°, about 8.4°, about 13.3°, about 13.9°, about 15.0°, about 15.2°, about 15.4°, about 16.1°, about 19.0°, about 19.5°, about 20.2°, about 20.7°, about 22.1°, about 22.5°, about 23.1°, about 24.0°, about 24.4°, and about 24.7°, about 25.4°, about 25.6°, about 25.9°, about 26.5°, about 26.7°, about 27.1°, about 27.3°, about 27.6°, about 28.5°, about 29.4°, about 29.6°, about 29.9°, about 30.1°, about 30.3°, about 30.6°, about 30.7°, about 31.1°, about 31.4°, about 32.2°, about 32.8°, about 33.1°, about 33.4°, about 33.6°, about 34.1°, about 34.3
  • Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 14.4° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at 8.5° ⁇ 0.2°, 9.0° ⁇ 0.2°, 11.5° ⁇ 0.2°, 14.1° ⁇ 0.2°, and 14.4° ⁇ 0.2° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.8° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.9° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.4° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.6° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.8° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 16.2°, about 16.9°, about 17.1°, about 19.8°, about 20.7°, about 21.4°, about 22.1°, about 23.1°, about 23.9°, and about 24.3° 2 ⁇ . [241] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.1°, about 25.3°, about 25.8°, about 27.1°, about 27.5°, about 27.7°, about 28.4°, about 29.5°, about 29.8°, about 31.0°, and about 34.9° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.1° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.8° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ⁇ 0.3° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.4° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.6° ⁇ 0.3° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.8° ⁇ 0.3° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 4.9° ⁇ 0.3°, 8.5° ⁇ 0.3°, 9.5° ⁇ 0.3°, 9.8° ⁇ 0.3°, 11.0° ⁇ 0.3°, 12.1° ⁇ 0.3°, 12.8° ⁇ 0.3°, 13.9° ⁇ 0.3°, 14.4° ⁇ 0.3°, and 14.8° ⁇ 0.3° 2 ⁇ .
  • SLU-030WO comprises one or more peaks selected from 16.2° ⁇ 0.3°, 16.9° ⁇ 0.3°, 17.1° ⁇ 0.3°, 19.8° ⁇ 0.3°, 20.7° ⁇ 0.3°, 21.4° ⁇ 0.3°, 22.1° ⁇ 0.3°, 23.1° ⁇ 0.3°, 23.9° ⁇ 0.3°, and 24.3° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.1° ⁇ 0.3°, 25.3° ⁇ 0.3°, 25.8° ⁇ 0.3°, 27.1° ⁇ 0.3°, 27.5° ⁇ 0.3°, 27.7° ⁇ 0.3°, 28.4° ⁇ 0.3°, 29.5° ⁇ 0.3°, 29.8° ⁇ 0.3°, 31.0° ⁇ 0.3°, and 34.9° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 26.3° ⁇ 0.3°, 26.6° ⁇ 0.3°, 26.7° ⁇ 0.3°, 27.9° ⁇ 0.3°, 28.1° ⁇ 0.3°, 28.7° ⁇ 0.3°, 28.9° ⁇ 0.3°, 29.1° ⁇ 0.3°, 30.2° ⁇ 0.3°, 30.7° ⁇ 0.3°, 31.3° ⁇ 0.3°, 31.6° ⁇ 0.3°, 31.8° ⁇ 0.3°, 32.2° ⁇ 0.3°, 32.6° ⁇ 0.3°, 33.1° ⁇ 0.3°, 33.4° ⁇ 0.3°, 33.8° ⁇ 0.3°, 34.0° ⁇ 0.3°, 34.2° ⁇ 0.3°, and 34.6° ⁇ 0.3° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising peaks at 4.9° ⁇ 0.3°, 8.5° ⁇ 0.3°, 9.5° ⁇ 0.3°, 9.8° ⁇ 0.3°, 11.0° ⁇ 0.3°, 12.1° ⁇ 0.3°, 12.8° ⁇ 0.3°, 13.9° ⁇ 0.3°, 14.4° ⁇ 0.3°, 14.8° ⁇ 0.3°, 15.2° ⁇ 0.3°, 16.2° ⁇ 0.3°, 16.3° ⁇ 0.3°, 16.5° ⁇ 0.3°, 16.9° ⁇ 0.3°, 17.1° ⁇ 0.3°, 17.5° ⁇ 0.3°, 18.0° ⁇ 0.3°, 19.0° ⁇ 0.3°, 19.1° ⁇ 0.3°, 19.8° ⁇ 0.3°, 20.2° ⁇ 0.3°, 20.4° ⁇ 0.3°, 20.7° ⁇ 0.3°, 21.0° ⁇ 0.3°,
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.1° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.8° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VII of the compound of Attorney Docket No.
  • SLU-030WO formula (I) has an XRPD pattern comprising a peak at 14.4° ⁇ 0.2° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.6° ⁇ 0.2° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.8° ⁇ 0.2° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 4.9° ⁇ 0.2°, 8.5° ⁇ 0.2°, 9.5° ⁇ 0.2°, 9.8° ⁇ 0.2°, 11.0° ⁇ 0.2°, 12.1° ⁇ 0.2°, 12.8° ⁇ 0.2°, 13.9° ⁇ 0.2°, 14.4° ⁇ 0.2°, and 14.8° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 15.2° ⁇ 0.2°, 16.3° ⁇ 0.2°, 16.5° ⁇ 0.2°, 17.5° ⁇ 0.2°, 18.0° ⁇ 0.2°, 19.0° ⁇ 0.2°, 19.1° ⁇ 0.2°, 20.2° ⁇ 0.2°, 20.4° ⁇ 0.2°, 21.0° ⁇ 0.2°, 21.6° ⁇ 0.2°, 22.5° ⁇ 0.2°, 23.7° ⁇ 0.2°, 24.5° ⁇ 0.2°, and 24.9° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 16.2° ⁇ 0.2°, 16.9° ⁇ 0.2°, 17.1° ⁇ 0.2°, 19.8° ⁇ 0.2°, 20.7° ⁇ 0.2°, 21.4° ⁇ 0.2°, 22.1° ⁇ 0.2°, 23.1° ⁇ 0.2°, 23.9° ⁇ 0.2°, and 24.3° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.1° ⁇ 0.2°, 25.3° ⁇ 0.2°, 25.8° ⁇ 0.2°, 27.1° ⁇ 0.2°, 27.5° ⁇ 0.2°, 27.7° ⁇ 0.2°, 28.4° ⁇ 0.2°, 29.5° ⁇ 0.2°, 29.8° ⁇ 0.2°, 31.0° ⁇ 0.2°, and 34.9° ⁇ 0.2° 2 ⁇ .
  • Form VII of the compound of formula (I) has an XRPD pattern comprising peaks at 4.9° ⁇ 0.2°, 8.5° ⁇ 0.2°, 9.5° ⁇ 0.2°, 9.8° ⁇ 0.2°, 11.0° ⁇ 0.2°, 12.1° ⁇ 0.2°, 12.8° ⁇ 0.2°, 13.9° ⁇ 0.2°, 14.4° ⁇ 0.2°, 14.8° ⁇ 0.2°, 15.2° ⁇ 0.2°, 16.2° ⁇ 0.2°, 16.3° ⁇ 0.2°, 16.5° ⁇ 0.2°, 16.9° ⁇ 0.2°, 17.1° ⁇ 0.2°, 17.5° ⁇ 0.2°, 18.0° ⁇ 0.2°, 19.0° ⁇ 0.2°, 19.1° ⁇ 0.2°, 19.8° ⁇ 0.2°, 20.2° ⁇ 0.2°, 20.4° ⁇ 0.2°, 20.7° ⁇ 0.2°, 21.0° ⁇ 0.2°,
  • Form VII of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2 ⁇ ) disclosed in Table 17. [252] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.7. [253] In certain embodiments, Form VII of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form VII of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group. In certain embodiments, Form VII of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 7.
  • Form VII of the compound of formula (I) further comprises water.
  • Form VII of the compound of formula (I) has a molar ratio of methanol to water of about 1:1.
  • Form VIII of a compound of formula (I) is a crystalline ethylene glycol solvate.
  • Form VIII of the compound of formula (I) is a crystalline mono-ethylene glycol solvate.
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 8.9° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.4° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern Attorney Docket No. SLU-030WO comprising a peak at about 13.1° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.0° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2 ⁇ .
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at about 8.9°, about 11.4°, about 13.1°, about 14.0°, and about 14.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 17.3°, about 18.8°, about 21.2°, about 21.9°, about 22.5°, about 23.7°, and about 24.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 16.9°, about 17.9°, about 20.3°, about 23.0°, about 23.2°, and about 24.0° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from about 25.3°, about 25.7°, about 26.1°, about 28.3°, about 29.3°, about 29.5°, and about 30.5° 2 ⁇ . In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.9°, about 26.4°, about 27.2°, about 27.9°, about 28.8°, about 29.0°, about 30.0°, about 30.9°, about 31.4°, about 31.6°, about 32.1°, about 32.4°, about 33.4°, about 34.0°, about 34.3°, and about 34.6° 2 ⁇ .
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at about 8.9°, about 11.4°, about 13.1°, about 14.0°, about 14.3°, about 16.0°, about 16.9°, about 17.3°, about 17.9°, about 18.8°, about 20.3°, about 21.2°, about 21.9°, about 22.5°, about 23.0°, about 23.2°, about 23.7°, about 24.0°, about 24.2°, about 25.3°, about 25.7°, about 25.9°, about 26.1°, about 26.4°, about 27.2°, about 27.9°, about 28.3°, about 28.8°, about 29.0°, about 29.3°, about 29.5°, about 30.0°, about 30.5°, about 30.9°, about 31.4°, about 31.6°, about 32.1°, about 32.4°, about 33.4°, about 34.0°, about 34.3°, and about 34.6° 2 ⁇ .
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ⁇ 0.3°, 11.4° ⁇ 0.3°, 13.1° ⁇ 0.3°, 14.0° ⁇ 0.3°, and 14.3° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 16.0° ⁇ 0.3°, 17.3° ⁇ 0.3°, 18.8° ⁇ 0.3°, 21.2° ⁇ 0.3°, 21.9° ⁇ 0.3°, 22.5° ⁇ 0.3°, 23.7° ⁇ 0.3°, and 24.2° ⁇ 0.3° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 16.9° ⁇ 0.3°, 17.9° ⁇ 0.3°, 20.3° ⁇ 0.3°, 23.0° ⁇ 0.3°, 23.2° ⁇ 0.3°, and 24.0° ⁇ 0.3° 2 ⁇ .
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ⁇ 0.3°, 11.4° ⁇ 0.3°, 13.1° ⁇ 0.3°, 14.0° ⁇ 0.3°, 14.3° ⁇ 0.3°, 16.0° ⁇ 0.3°, 16.9° ⁇ 0.3°, 17.3° ⁇ 0.3°, 17.9° ⁇ 0.3°, 18.8° ⁇ 0.3°, 20.3° ⁇ 0.3°, 21.2° ⁇ 0.3°, 21.9° ⁇ 0.3°, 22.5° ⁇ 0.3°, 23.0° ⁇ 0.3°, 23.2° ⁇ 0.3°, 23.7° ⁇ 0.3°, 24.0° ⁇ 0.3°, 24.2° ⁇ 0.3°, 25.3° ⁇ 0.3°, 25.7° ⁇ 0.3°, 25.9° ⁇ 0.3°, 26.1° ⁇ 0.3°, 26.4° ⁇ 0.3°, 27.2° ⁇ 0.3°
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 8.9° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.4° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.1° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.0° ⁇ 0.2° 2 ⁇ .
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ⁇ 0.2° 2 ⁇ . In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ⁇ 0.2°, 11.4° ⁇ 0.2°, 13.1° ⁇ 0.2°, 14.0° ⁇ 0.2°, and 14.3° ⁇ 0.2° 2 ⁇ .
  • the XRPD pattern further comprises one or more peaks selected from 25.3° ⁇ 0.2°, 25.7° ⁇ 0.2°, 26.1° ⁇ 0.2°, 28.3° ⁇ 0.2°, 29.3° ⁇ 0.2°, 29.5° ⁇ 0.2°, and 30.5° ⁇ 0.2° 2 ⁇ .
  • Form VIII of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2 ⁇ ) disclosed in Table 18. [270] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.8. [271] In certain embodiments, Form VIII of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form VIII of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. In certain embodiments, Form VIII of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 8. Attorney Docket No.
  • Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 9.5° 2 ⁇ . In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.5° 2 ⁇ . In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.1° 2 ⁇ . In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2 ⁇ .
  • a crystalline form of a compound of formula (I) described herein has a chemical purity of about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to Attorney Docket No.
  • SLU-030WO about 100%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%.
  • the amounts of the compound of formula (I) may vary depending upon the patient being treated and/or the particular mode of administration.
  • excipients suitable for use in oral liquid or aerosol dosage forms include, but are not limited to, water, glycols, oils, alcohols, flavoring agents, preservatives, and coloring agents.
  • excipients suitable for use in solid oral dosage forms include, but are not limited to, fillers, diluents, granulating agents, lubricants, binders, and disintegrating agents.
  • the pharmaceutical compositions described herein may be in the form of an oral dosage form, such as a tablet or a capsule, in which case solid excipients are employed.
  • the tablets can be coated by standard aqueous or nonaqueous techniques.
  • Example 1 Synthesis of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 H]-2,6- piperidinedione [313] Reaction temperatures are reported as internal temperatures. Chemical intermediates, reagents, and solvents were obtained from commercial sources. Preparation of 2-methyl-6-nitro-4H-3,1-benzoxazin-4-one [314] 2-Amino-5- was mixed with acetic anhydride (800 mL, 8.47 mol, 3.86 eq.) and then heated to 120°C in an oil bath for 2 hours. The resulting mixture was cooled to 25 ⁇ 5°C overnight.
  • acetic anhydride 800 mL, 8.47 mol, 3.86 eq.
  • T3P Propylphosphonic anhydride
  • ethyl acetate 2.478 L, 4.16 mol, 2.0 eq.
  • isopropyl acetate 500 mL
  • the resulting mixture was heated to 88 ⁇ 5°C.
  • additional T3P in ethyl acetate 197 mL, 0.15 eq.
  • the mixture was cooled to 25 ⁇ 5°C and the solid material was collected by filtration.
  • the remaining MeTHF was then added to the reactor, followed by 1.86 L (6.5 vol.) of an 8% sodium bicarbonate solution in water. The mixture was stirred for 5 min then left to settle for 5 min. The aqueous layer was separated and then extracted twice with additional MeTHF (1.8 L, 6.5 vol.). The organic layer was combined with the MeTHF extractions and washed with a 4% sodium bicarbonate solution (435 mL,1.5 vol) and deionized water (580 mL, 2 vol.), twice sequentially. The organic phase was then concentrated by vacuum distillation to ⁇ 900mL (3 vol.) while keeping the temperature below 35°C (the max. observed temperature was 25°C).
  • the batch was then concentrated to ⁇ 2.5 L (8.5 vol.) by evaporation under reduced pressure while keeping the temperature below 35 °C.
  • the resulting mixture was stirred at 20 °C for 1 h.
  • the solid was collected by filtration and rinsed with IPA (twice 290mL, 1 vol.).
  • the wet cake was dried under reduced pressure with a nitrogen sweep at 25 ⁇ 5 °C for 18 h to give the title compound as a crystalline off-white solid (105 g).
  • Form II was prepared as follows. SP-3164 (596 g MeTHF solution containing 8.7 g the free base of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 H]-2,6- piperidinedione, prepared as described in Example 1 and obtained during the isolation of the free base by extraction) was concentrated to 50 g under reduced pressure. MeTHF (140 mL) was added, and the mixture was further concentrated to about 25 g.

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Abstract

Provided herein are crystalline forms of the compound of formula (I) and compositions thereof.

Description

Attorney Docket No. SLU-030WO SOLID FORMS AND METHODS OF USE CROSS REFERENCE TO RELATED APPLICATIONS [001] This application claims the benefit of, and priority to, U.S. Provisional Patent Application No.63/437,527, filed January 6, 2023, the contents of which are incorporated by reference herein in their entirety. BACKGROUND [002] Deuterium-enriched enantiomers of drug compounds are believed to be useful in the treatment of a wide range of human diseases, including but not limited to, cancer, inflammatory diseases, and immune-mediated disorders. Developing solid forms of these deuterium-enriched enantiomers, however, that provide the physicochemical properties necessary to manufacture a commercial drug product with the required efficacy remains a significant challenge. This is due to the unpredictability in the outcome of solid form screening for any given compound and the subsequent unpredictability of the physicochemical properties of any solid forms discovered. Thus, there is an unmet need for new solid forms of deuterium-enriched compounds that achieve the required physicochemical properties necessary to provide therapeutic properties over the non-deuterated versions. SUMMARY [003] In one aspect, provided herein are crystalline forms of the compound of formula (I) N CH3 .
Figure imgf000002_0001
[004] In another aspect, provided herein are anhydrous crystalline forms of the compound of formula (I) Attorney Docket No. SLU-030WO . [005] In various of formula (I)
Figure imgf000003_0001
. [006] In various compound of formula (I)
Figure imgf000003_0002
. [007] In various compound of formula (I)
Figure imgf000003_0003
. [008] In another aspect,
Figure imgf000003_0004
of a compound of formula (I) .
Figure imgf000003_0005
[009] In various embodiments, provided herein is Form II of a compound of formula (I) Attorney Docket No. SLU-030WO N CH3 . [010] In another aspect, generally comprising a crystalline
Figure imgf000004_0001
herein, and a pharmaceutically acceptable excipient. [011] In various embodiments, provided herein is a pharmaceutical composition comprising an anhydrous crystalline form of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient. In various embodiments, provided herein is a pharmaceutical composition comprising the Form I of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient. In various embodiments, provided herein is a pharmaceutical composition comprising the Form II of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient. In various embodiments, provided herein is a pharmaceutical composition comprising the Form III of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient. In various embodiments, provided herein is a pharmaceutical composition comprising the Form X of the compound of formula (I) described herein; and a pharmaceutically acceptable excipient. BRIEF DESCRIPTION OF THE DRAWINGS [012] FIG.1A is an X-ray powder diffraction (XRPD) pattern of Form I of the compound of formula (I) calculated from single crystal X-ray diffraction (XRD) data, as further described in Example 2. [013] FIG.1B is an overlay of an XRPD pattern of Form I of the compound of formula (I) calculated from single crystal XRD data and an exemplary experimental XRPD pattern of Form I of a compound of formula (I). [014] FIG.1C is an exemplary XRPD pattern of Form I of the compound of formula (I). [015] FIG.2 is an XRPD pattern of Form II of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [016] FIG.3 is an XRPD pattern of Form III of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. Attorney Docket No. SLU-030WO [017] FIG.4 is an XRPD pattern of Form IV of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [018] FIG.5 is an XRPD pattern of Form V of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [019] FIG.6 is an XRPD pattern of Form VI of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [020] FIG.7 is an XRPD pattern of Form VII of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [021] FIG.8 is an XRPD pattern of Form VIII of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [022] FIG.9 is an XRPD pattern of Form IX of the compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [023] FIG.10 is an exemplary XRPD pattern of Form X of the compound of formula (I). [024] FIG.11 is an Oak Ridge Thermal Ellipsoid Plot (ORTEP) diagram for Form I of the compound of formula (I). [025] FIG.12 is an ORTEP diagram for Form II of the compound of formula (I). [026] FIG.13 is an ORTEP diagram for Form III of the compound of formula (I). [027] FIG.14 is an ORTEP diagram for Form IV of the compound of formula (I). [028] FIG.15 is an ORTEP diagram for Form V of the compound of formula (I). [029] FIG.16 is an ORTEP diagram for Form VI of the compound of formula (I). [030] FIG.17 is an ORTEP diagram for Form VII of the compound of formula (I). [031] FIG.18 is an ORTEP diagram for Form VIII of the compound of formula (I). [032] FIG.19 is an ORTEP diagram for Form IX of the compound of formula (I). [033] FIG.20 is an overlay of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) thermograms for Form I of the compound of formula (I). [034] FIG.21 is an exemplary water sorption isotherm recorded at 25℃ for Form I of the compound of formula (I). [035] FIG.22 is an overlay of DSC and TGA thermograms for Form X of the compound of formula (I). [036] FIG.23 is an exemplary water sorption isotherm recorded at 25℃ for Form X of the compound of formula (I). Attorney Docket No. SLU-030WO [037] FIG.24 is an exemplary XRPD pattern of the crystalline material prepared as described in Example 1 showing a mixture of Forms I and II of the compound of formula (I). [038] FIG.25 is an exemplary DSC thermogram for the crystalline material of the compound of formula (I) prepared as described in Example 1. [039] FIG.26 is an exemplary TGA thermogram for the crystalline material of the compound of formula (I) prepared as described in Example 1. [040] FIG.27 shows the plasma pharmacokinetic (PK) profiles (concentration vs. time) in mice of the protonated and deuterated (R)- and (S)-enantiomers of 3-(5-amino-2-methyl-4- oxo-3H-quinazolin-3-yl)-2,6-piperidinedione, as appropriate, after oral administration of a single dose of the compound of formula (I) (15 mg/kg, top) or the corresponding protonated racemic mixture, avadomide (30 mg/kg, bottom), administered at equivalent doses, where h- R stands for the protonated (R)-enantiomer; h-S, for the protonated (S)-enantiomer; d-R, for the deuterated (R)-enantiomer and d-S, for the deuterated (S)-enantiomer. p.o. = by mouth, C = concentration [041] FIG.28 shows the plasma PK profiles (concentration vs. time) in rats of the protonated and deuterated (R)- and (S)-enantiomers of 3-(5-amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-2,6-piperidinedione, as appropriate, after oral administration of a single dose of the compound of formula (I) (150 mg/kg, top) or the corresponding protonated racemic mixture, avadomide (300 mg/kg, bottom), administered at equivalent doses, where h-S stands for the protonated (S)-enantiomer; h-R, for the protonated (R)-enantiomer; and d-S, for the deuterated (S)-enantiomer. p.o. = by mouth, C = concentration [042] FIG.29 shows the plasma PK profiles (concentration vs. time) in cynomolgus monkeys of the protonated and deuterated (R)- and (S)-enantiomers of 3-(5-amino-2-methyl- 4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione, as appropriate, after oral administration of a single dose of the compound of formula (I) (0.25 mg/kg, top; 0.75 mg/kg, middle) or the corresponding protonated racemic mixture, avadomide (1.5 mg/kg, bottom), where h-S stands for the protonated (S)-enantiomer; h-R, for the protonated (R)-enantiomer; and d-S, for the deuterated (S)-enantiomer. p.o. = by mouth, C = concentration Attorney Docket No. SLU-030WO DETAILED DESCRIPTION [043] As generally described herein, the disclosure provides pharmaceutically acceptable forms of deuterium-enriched (S)-avadomide (e.g., crystalline forms of deuterium-enriched (S)-avadomide), also referred to herein as a compound of formula (I), and pharmaceutical compositions containing the same. In particular, the invention provides crystalline forms of deuterium-enriched (S)-avadomide with unexpectedly improved solubilities at physiologically relevant pHs and in vivo bioavailability compared to avadomide (racemic). Definitions [044] To facilitate an understanding of the present invention, a number of terms and phrases are defined below. [045] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. [046] Throughout the description, where compositions and kits are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions and kits of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps. [047] In the application, where an element or component is said to be included in and/or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components. [048] Further, it should be understood that elements and/or features of a composition or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present invention, whether explicit or implicit herein. For example, where reference is made to a particular compound, that compound can be used in various embodiments of compositions of the present invention and/or in methods of the present Attorney Docket No. SLU-030WO invention, unless otherwise understood from the context. In other words, within this application, embodiments have been described and depicted in a way that enables a clear and concise application to be written and drawn, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the present teachings and invention(s). For example, it will be appreciated that all features described and depicted herein can be applicable to all aspects of the invention(s) described and depicted herein. [049] The articles “a” and “an” are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article, unless the context is inappropriate. By way of example, “an element” means one element or more than one element. [050] The term “and/or” is used in this disclosure to mean either “and” or “or” unless indicated otherwise. [051] It should be understood that the expression “at least one of” includes individually each of the recited objects after the expression and the various combinations of two or more of the recited objects unless otherwise understood from the context and use. The expression “and/or” in connection with three or more recited objects should be understood to have the same meaning unless otherwise understood from the context. [052] The use of the term “include,” “includes,” “including,” “have,” “has,” “having,” “contain,” “contains,” or “containing,” including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context. [053] Where the use of the term “about” is before a quantitative value, the present invention also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ±10%, ±5%, ±3%, ±2%, or ±1% variation from the nominal value unless otherwise indicated or inferred from the context. [054] Due to sources of experimental variability that are well known to those of ordinary skill in the art, the values of each XRPD peak are typically preceded with the term “about” or proceeded with an appropriate range defining the experimental variability. For purposes of data reported herein, that value is ±0.3° 2θ unless otherwise stated. XRPD peaks cited herein are generally reported with this variability of ±0.3° 2θ unless stated otherwise and are Attorney Docket No. SLU-030WO intended to be reported with such a variability whenever disclosed herein whether the word “about” is present or not, unless context dictates otherwise. [055] Due to sources of experimental variability that are well known to those of ordinary skill in the art, the values of each differential scanning calorimetry (DSC) endotherm or exotherm are typically preceded with the term “about” or proceeded with an appropriate range defining the experimental variability. For purposes of data reported herein, that value is ±10 °C unless otherwise stated. DSC endotherms/exotherms cited herein are generally reported with this variability of ±10 °C unless stated otherwise and are intended to be reported with such a variability whenever disclosed herein whether the word “about” is present or not, unless context dictates otherwise. [056] At various places in the present specification, variable or parameters are disclosed in groups or in ranges. It is specifically intended that the description include each and every individual sub-combination of the members of such groups and ranges. For example, an integer in the range of 0 to 40 is specifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40, and an integer in the range of 1 to 20 is specifically intended to individually disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. [057] The use of any and all examples, or exemplary language herein, for example, “such as” or “including,” is intended merely to illustrate better the present invention and does not pose a limitation on the scope of the invention unless claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the present invention. [058] Deuterium, which may also be referred to herein as 2H and/or D, is a stable, non- radioactive isotope of hydrogen and has an atomic weight of 2.014. Hydrogen naturally occurs as a mixture of the isotopes 1H hydrogen (i.e., protium), deuterium (2H), and tritium (3H). The natural abundance of deuterium is about 0.015%. One of ordinary skill in the art recognizes that in all chemical compounds with an H atom, the H atom actually represents a mixture of 1H hydrogen, deuterium (2H), and tritium (3H), where about 0.015% is deuterium. In various embodiments, compounds with a level of deuterium that has been enriched to be greater than its natural abundance of about 0.015% are considered unnatural and, as a result, novel over their non-enriched counterparts. In certain embodiments, compounds with a level Attorney Docket No. SLU-030WO of deuterium that has been enriched to be greater than its natural abundance of about 0.015% is a deuterium-enriched compound. [059] As used herein, “total deuterium content” or “total deuterium abundance” refer to number of deuteriums that are present in a molecule. The total deuterium content may be determined, for example, by a 2H-NMR. The deuterium content at the chiral center of a molecule (e.g., deuterium-enriched compound of formula (I)) may be determined, for an example, using 1H-NMR. [060] As a general matter, compositions specifying a percentage are by weight unless otherwise specified. Further, if a variable is not accompanied by a definition, then the previous definition of the variable controls. [061] As used herein, “pharmaceutical composition” or “pharmaceutical formulation” refers to the combination of an active agent with a carrier, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo or ex vivo. [062] “Pharmaceutically acceptable” means approved or approvable by a regulatory agency of the federal or a state government or the corresponding agency in countries other than the United States, or that is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly, in humans. [063] As used herein, “pharmaceutically acceptable excipient” refers to a substance that aids the administration of an active agent to and/or absorption by a subject and can be included in the compositions of the present invention without causing a significant adverse toxicological effect on the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, such as a phosphate buffered saline solution, emulsions (e.g., oil/water or water/oil emulsions), lactated Ringer’s, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer’s solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with the compounds of the invention. For examples of excipients, see Martin, Remington’s Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA (1975). Attorney Docket No. SLU-030WO [064] As used herein, “solid dosage form” means a pharmaceutical dose(s) in solid form, e.g., tablets, capsules, granules, powders, sachets, reconstitutable powders, dry powder inhalers and chewables. [065] As used herein, “administering” means oral administration, administration as a suppository, topical contact, intravenous administration, parenteral administration, intraperitoneal administration, intramuscular administration, intralesional administration, intrathecal administration, intracranial administration, intranasal administration or subcutaneous administration, or the implantation of a slow-release device, e.g., a mini- osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra- arterial, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. By “co-administer” it is meant that a composition described herein is administered at the same time, just prior to, or just after the administration of one or more additional therapies (e.g., anti-cancer agent, chemotherapeutic, or treatment for a neurodegenerative disease). Compounds of the disclosure, or a pharmaceutically acceptable salt thereof, can be administered alone or can be co-administered to the patient. Co-administration is meant to include simultaneous or sequential administration of the compound individually or in combination (more than one compound or agent). Thus, the preparations can also be combined, when desired, with other active substances (e.g., to reduce metabolic degradation). [066] The terms “disease,” “disorder,” and “condition” are used interchangeably herein. [067] As used herein, and unless otherwise specified, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified disease, disorder, or condition, which reduces the severity of the disease, disorder, or condition, or retards or slows the progression of the disease, disorder, or condition (e.g., “therapeutic treatment”). [068] In general, an “effective amount” of a compound refers to an amount sufficient to elicit the desired biological response, e.g., to treat a condition, disease, or disorder described herein. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound of the disclosure may vary depending on such factors as the desired biological Attorney Docket No. SLU-030WO endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, weight, health, and condition of the subject. Deuterium-Enriched Compounds [069] Deuterium-enriched compounds of the disclosure are depicted in formula (I): N CH3 . [070] A compound of as (S)-3-(2-methyl-5-
Figure imgf000012_0001
amino-4-oxo-3H- - - or deuterium-enriched (S)- avadomide. [071] As depicted above, the deuterium-enriched compounds described herein contain deuterium enrichment at the chiral center. Without wishing to be bound by theory, it is thought that deuterium-enrichment at the chiral center may reduce or inhibit the rate at which the two enantiomers may interconvert. [072] Methods of chemically synthesizing the compound of formula (I) and preparing the crystalline forms described herein are provided in Examples 1-3. [073] In certain embodiments, the abundance of deuterium at the chiral center is about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100%, about 30% to about 95%, about 30% to about 90%, about 30% to about 85%, about 30% to about 80%, about 30% to about 75%, about 30% to about 70%, about 30% to about 60%, about 30% to about 50%, about 30% to about 40%, about 40% to about 95%, about 40% to about 90%, about 40% to about 85%, about 40% to about 80%, about 40% to about 75%, about 40% to about 70%, about 40% to about 60%, about 40% to about 50%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 60%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to Attorney Docket No. SLU-030WO about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%. [074] In certain embodiments, the abundance of deuterium at the chiral center is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. [075] In certain embodiments, the abundance of deuterium at the chiral center is about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100%. [076] In certain embodiments, the deuterium-enriched compound of formula (I) described herein has an enantiomeric excess (enantiomeric excess (ee in %) is defined as the difference between mole percent of each enantiomer in a mixture of both, e.g., if %S > %R, ee = %S - %R) of about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%. [077] In certain embodiments, the deuterium-enriched compound of formula (I) described herein has an enantiomeric excess of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. Attorney Docket No. SLU-030WO [078] In certain embodiments, the deuterium-enriched compound of formula (I) described herein has an enantiomeric excess of about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100%. In certain embodiments, the deuterium- enriched compound of formula (I) described herein is enantiopure. [079] In various embodiments, provided herein is a crystalline form of the compound of formula (I). Crystalline Forms of the Deuterium-Enriched Compound of Formula (I) [080] In one aspect, provided herein is a crystalline form of a compound of formula (I): N CH3 . [081] In certain of formula (I) has an
Figure imgf000014_0001
XRPD pattern comprising a peak at about 11.0° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 11.0°, about 11.9°, and about 14.1° 2θ. [082] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.7°, about 21.1°, about 21.5°, about 23.5°, about 24.0°, and about 24.7° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.9°, about 29.2°, about 31.1°, about 32.5°, about 33.7°, and about 34.5° 2θ. [083] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 11.0°, about 11.9°, about 14.1°, about 15.3°, about 19.7°, about 21.1°, about 21.5°, about 23.5°, about 24.0°, about 24.7°, about 26.4°, about 27.1°, about 28.9°, about 29.2°, about 31.1°, about 32.5°, about 33.7°, and about 34.5° 2θ. Attorney Docket No. SLU-030WO [084] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ± 0.3° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.3° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.3° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ± 0.3°, 11.9° ± 0.3°, and 14.1° ± 0.3° 2θ. [085] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.3°, 19.7° ± 0.3°, 21.1° ± 0.3°, 21.5° ± 0.3°, 23.5° ± 0.3°, 24.0° ± 0.3°, and 24.7° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4° ± 0.3°, 27.1° ± 0.3°, 28.9° ± 0.3°, 29.2° ± 0.3°, 31.1° ± 0.3°, 32.5° ± 0.3°, 33.7° ± 0.3°, and 34.5° ± 0.3° 2θ. [086] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ± 0.3°, 11.9° ± 0.3°, 14.1° ± 0.3°, 15.3° ± 0.3°, 19.7° ± 0.3°, 21.1° ± 0.3°, 21.5° ± 0.3°, 23.5° ± 0.3°, 24.0° ± 0.3°, 24.7° ± 0.3°, 26.4° ± 0.3°, 27.1° ± 0.3°, 28.9° ± 0.3°, 29.2° ± 0.3°, 31.1° ± 0.3°, 32.5° ± 0.3°, 33.7° ± 0.3°, and 34.5° ± 0.3° 2θ. [087] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ± 0.2° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.2° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.2° 2θ. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ± 0.2°, 11.9° ± 0.2°, and 14.1° ± 0.2° 2θ. [088] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.3°, 19.7° ± 0.2°, 21.1° ± 0.2°, 21.5° ± 0.2°, 23.5° ± 0.2°, 24.0° ± 0.2°, and 24.7° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4° ± 0.2°, 27.1° ± 0.2°, 28.9° ± 0.2°, 29.2° ± 0.2°, 31.1° ± 0.2°, 32.5° ± 0.2°, 33.7° ± 0.2°, and 34.5° ± 0.2° 2θ. [089] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ± 0.2°, 11.9° ± 0.2°, 14.1° ± 0.2°, 15.3° ± 0.2°, 19.7° ± 0.2°, 21.1° ± 0.2°, 21.5° ± 0.2°, 23.5° ± 0.2°, 24.0° ± 0.2°, 24.7° ± 0.2°, 26.4° ± 0.2°, Attorney Docket No. SLU-030WO 27.1° ± 0.2°, 28.9° ± 0.2°, 29.2° ± 0.2°, 31.1° ± 0.2°, 32.5° ± 0.2°, 33.7° ± 0.2°, and 34.5° ± 0.2° 2θ. [090] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 11. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 12. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 13. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 14. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 15. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 16. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 17. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 18. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 19. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 20. [091] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1A. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.2. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.4. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.5. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.6. In certain embodiments, the crystalline Attorney Docket No. SLU-030WO form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.7. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.8. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.9. In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.10. [092] In certain embodiments, the crystalline form of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, the crystalline form of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group. In certain embodiments, the crystalline form of the compound of formula (I) exists in an orthorhombic crystal system and has a C2221 space group. [093] In certain embodiments, the crystalline form of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, the crystalline form of the compound of formula (I) exists in a monoclinic crystal system and has a P121/n1 space group. In certain embodiments, the crystalline form of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. [094] In certain embodiments, the crystalline form of the compound of formula (I) is an anhydrous crystalline form. In certain embodiments, the crystalline form of the compound of formula (I) is a crystalline hydrate. In certain embodiments, the crystalline form of the compound of formula (I) is a crystalline solvate. (1) Anhydrous Crystalline Forms of a Compound of Formula (I) [095] In one aspect, provided herein are anhydrous crystalline forms of a compound of formula (I). [096] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.9°, about 11.9°, and about 14.1° 2θ. Attorney Docket No. SLU-030WO [097] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 18.7°, about 19.7°, about 21.2°, about 21.6°, about 23.3°, about 24.1°, and about 24.6° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.8°, about 29.2°, about 30.6°, about 31.1°, about 32.4°, about 33.0°, about 33.8°, and about 34.7° 2θ. [098] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.9°, about 11.9°, about 14.1°, about 15.3°, about 18.7°, about 19.7°, about 21.2°, about 21.6°, about 23.3°, about 24.1°, about 24.6°, about 26.4°, about 27.1°, about 28.8°, about 29.2°, about 30.6°, about 31.1°, about 32.4°, about 33.0°, about 33.8°, and about 34.7° 2θ. [099] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ± 0.3° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.3° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ± 0.3° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 10.9° ± 0.3°, 11.9° ± 0.3°, and 14.1° ± 0.3° 2θ. [100] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.3°, 18.7° ± 0.3°, 19.7° ± 0.3°, 21.2° ± 0.3°, 21.6° ± 0.3°, 23.3° ± 0.3°, 24.1° ± 0.3°, and 24.6° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4° ± 0.3°, 27.1° ± 0.3°, 28.8° ± 0.3°, 29.2° ± 0.3°, 30.6° ± 0.3°, 31.1° ± 0.3°, 32.4° ± 0.3°, 33.0° ± 0.3°, 33.8° ± 0.3°, and 34.7° ± 0.3° 2θ. [101] In certain embodiments, the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 10.9° ± 0.3°, 11.9° ± 0.3°, 14.1° ± 0.3°, 15.3° ± 0.3°, 18.7° ± 0.3°, 19.7° ± 0.3°, 21.2° ± 0.3°, 21.6° ± 0.3°, 23.3° ± 0.3°, 24.1° ± 0.3°, 24.6° ± 0.3°, 26.4° ± 0.3°, 27.1° ± 0.3°, 28.8° ± 0.3°, 29.2° ± 0.3°, 30.6° ± 0.3°, 31.1° ± 0.3°, 32.4° ± 0.3°, 33.0° ± 0.3°, 33.8° ± 0.3°, and 34.7° ± 0.3° 2θ. [102] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ± 0.2° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.2° 2θ. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.2° 2θ. In Attorney Docket No. SLU-030WO certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 10.9° ± 0.2°, 11.9° ± 0.2°, and 14.1° ± 0.2° 2θ. [103] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.2°, 18.7° ± 0.2°, 19.7° ± 0.2°, 21.2° ± 0.2°, 21.6° ± 0.2°, 23.3° ± 0.2°, 24.1° ± 0.2°, and 24.6° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4° ± 0.2°, 27.1° ± 0.2°, 28.8° ± 0.2°, 29.2° ± 0.2°, 30.6° ± 0.2°, 31.1° ± 0.2°, 32.4° ± 0.2°, 33.0° ± 0.2°, 33.8° ± 0.2°, and 34.7° ± 0.2° 2θ. [104] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at 10.9° ± 0.2°, 11.9° ± 0.2°, 14.1° ± 0.2°, 15.3° ± 0.2°, 18.7° ± 0.2°, 19.7° ± 0.2°, 21.2° ± 0.2°, 21.6° ± 0.2°, 23.3° ± 0.2°, 24.1° ± 0.2°, 24.6° ± 0.2°, 26.4° ± 0.2°, 27.1° ± 0.2°, 28.8° ± 0.2°, 29.2° ± 0.2°, 30.6° ± 0.2°, 31.1° ± 0.2°, 32.4° ± 0.2°, 33.0° ± 0.2°, 33.8° ± 0.2°, and 34.7° ± 0.2° 2θ. [105] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 11. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 13. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 20. [106] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1A. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.10. [107] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group. [108] In certain embodiments, the anhydrous crystalline form of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, the anhydrous crystalline form of the compound of formula (I) exists in a monoclinic crystal system and has a P121/n1 space group. Attorney Docket No. SLU-030WO (A) Form I [109] In one aspect, provided herein is Form I of a compound of formula (I). [110] In certain embodiments, Form I of the compound of formula (I) is an anhydrous crystalline form. [111] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.0° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.7° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.0° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.8° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.0° and about 14.0° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising one or more peaks selected from about 10.3°, about 11.0°, about 11.9°, about 13.7°, about 14.0°, and about 14.8° 2θ. [112] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 17.4°, about 20.6°, about 21.1°, about 23.2°, and about 24.1° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 17.6°, about 18.7°, about 19.7°, about 21.6°, about 23.0°, about 23.7°, and about 24.6° 2θ. [113] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.8°, about 28.2°, about 30.3°, about 30.5°, and about 33.0° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.6°, about 27.1°, about 28.9°, about 29.2°, about 30.9°, about 31.1°, about 32.1°, about 32.4°, about 33.8°, about 34.0°, about 34.5°, and about 34.7° 2θ. [114] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.3°, about 11.0°, about 11.9°, about 13.7°, about 14.0°, about 14.8°, about 15.3°, about 17.4°, 17.6°, about 18.7°, about 19.7°, about 20.6°, about 21.1°, Attorney Docket No. SLU-030WO about 21.6°, about 23.0°, about 23.2°, about 23.7°, about 24.1°, about 24.6°, about 25.6°, about 26.1°, about 26.4°, about 26.8°, about 27.1°, about 28.2°, about 28.9°, about 29.2°, about 30.3°, about 30.5°, about 30.9°, about 31.1°, about 32.1°, about 32.4°, about 33.0°, about 33.8°, about 34.0°, about 34.5°, and about 34.7° 2θ. [115] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 10.3° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 13.7° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 14.0° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 14.8° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ± 0.3° and 14.0° ± 0.3° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising one or more peaks selected from 10.3° ± 0.3°, 11.0° ± 0.3°, 11.9° ± 0.3°, 13.7° ± 0.3°, 14.0° ± 0.3°, and 14.8° ± 0.3° 2θ. [116] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.3°, 17.4° ± 0.3°, 20.6° ± 0.3°, 21.1° ± 0.3°, 23.2° ± 0.3°, and 24.1° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.6° ± 0.3°, 18.7° ± 0.3°, 19.7° ± 0.3°, 21.6° ± 0.3°, 23.0° ± 0.3°, 23.7° ± 0.3°, and 24.6° ± 0.3° 2θ. [117] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1° ± 0.3°, 26.4° ± 0.3°, 26.8° ± 0.3°, 28.2° ± 0.3°, 30.3° ± 0.3°, 30.5° ± 0.3°, and 33.0° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6° ± 0.3°, 27.1° ± 0.3°, 28.9° ± 0.3°, 29.2° ± 0.3°, 30.9° ± 0.3°, 31.1° ± 0.3°, 32.1° ± 0.3°, 32.4° ± 0.3°, 33.8° ± 0.3°, 34.0° ± 0.3°, 34.5° ± 0.3°, and 34.7° ± 0.3° 2θ. [118] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 10.3° ± 0.3°, 11.0° ± 0.3°, 11.9° ± 0.3°, 13.7° ± 0.3°, 14.0° ± 0.3°, 14.8° ± 0.3°, 15.3° ± 0.3°, 17.4° ± 0.3°, 17.6° ± 0.3°, 18.7° ± 0.3°, 19.7° ± 0.3°, 20.6° ± 0.3°, 21.1° ± 0.3°, 21.6° ± 0.3°, 23.0° ± 0.3°, 23.2° ± 0.3°, 23.7° ± 0.3°, 24.1° ± 0.3°, 24.6° ± 0.3°, 25.6° Attorney Docket No. SLU-030WO ± 0.3°, 26.1° ± 0.3°, 26.4° ± 0.3°, 26.8° ± 0.3°, 27.1° ± 0.3°, 28.2° ± 0.3°, 28.9° ± 0.3°, 29.2° ± 0.3°, 30.3° ± 0.3°, 30.5° ± 0.3°, 30.9° ± 0.3°, 31.1° ± 0.3°, 32.1° ± 0.3°, 32.4° ± 0.3°, 33.0° ± 0.3°, 33.8° ± 0.3°, 34.0° ± 0.3°, 34.5° ± 0.3°, and 34.7° ± 0.3° 2θ. [119] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 10.3° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 13.7° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 14.0° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 14.8° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising peaks at 11.0° ± 0.2° and 14.0° ± 0.2° 2θ. In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising one or more peaks selected from 10.3° ± 0.2°, 11.0° ± 0.2°, 11.9° ± 0.2°, 13.7° ± 0.2°, 14.0° ± 0.2°, and 14.8° ± 0.2° 2θ. [120] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.2°, 17.4° ± 0.2°, 20.6° ± 0.2°, 21.1° ± 0.2°, 23.2° ± 0.2°, and 24.1° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.6° ± 0.2°, 18.7° ± 0.2°, 19.7° ± 0.2°, 21.6° ± 0.2°, 23.0° ± 0.2°, 23.7° ± 0.2°, and 24.6° ± 0.2° 2θ. [121] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1° ± 0.2°, 26.4° ± 0.2°, 26.8° ± 0.2°, 28.2° ± 0.2°, 30.3° ± 0.2°, 30.5° ± 0.2°, and 33.0° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6° ± 0.2°, 27.1° ± 0.2°, 28.9° ± 0.2°, 29.2° ± 0.2°, 30.9° ± 0.2°, 31.1° ± 0.2°, 32.1° ± 0.2°, 32.4° ± 0.2°, 33.8° ± 0.2°, 34.0° ± 0.2°, 34.5° ± 0.2°, and 34.7° ± 0.2° 2θ. [122] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising a peak at 10.3° ± 0.2°, 11.0° ± 0.2°, 11.9° ± 0.2°, 13.7° ± 0.2°, 14.0° ± 0.2°, 14.8° ± 0.2°, 15.3° ± 0.2°, 17.4° ± 0.2°, 17.6° ± 0.2°, 18.7° ± 0.2°, 19.7° ± 0.2°, 20.6° ± 0.2°, 21.1° ± 0.2°, 21.6° ± 0.2°, 23.0° ± 0.2°, 23.2° ± 0.2°, 23.7° ± 0.2°, 24.1° ± 0.2°, 24.6° ± 0.2°, 25.6° ± 0.2°, 26.1° ± 0.2°, 26.4° ± 0.2°, 26.8° ± 0.2°, 27.1° ± 0.2°, 28.2° ± 0.2°, 28.9° ± 0.2°, 29.2° Attorney Docket No. SLU-030WO ± 0.2°, 30.3° ± 0.2°, 30.5° ± 0.2°, 30.9° ± 0.2°, 31.1° ± 0.2°, 32.1° ± 0.2°, 32.4° ± 0.2°, 33.0° ± 0.2°, 33.8° ± 0.2°, 34.0° ± 0.2°, 34.5° ± 0.2°, and 34.7° ± 0.2° 2θ. [123] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 11. [124] In certain embodiments, Form I of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1A. [125] In certain embodiments, Form I of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form I of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group. In certain embodiments, Form I of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 1. Table 1 – Unit Cell Parameters of Form I of the Compound of Formula (I) a [Å] 8.3457(4) b [Å] 102066(5) ) [126] In certain embodiments,
Figure imgf000023_0001
Form I of the compound of formula (I) has a differential scanning calorimetry (DSC) thermogram comprising an endotherm with a peak onset at about 238 °C. In certain embodiments, Form I of the compound of formula (I) has a DSC thermogram comprising an endotherm with a peak onset at about 273.9 °C. In certain embodiments, Form I of the compound of formula (I) has a DSC thermogram comprising one or more endotherms with peak onsets at about 238 °C and about 273.9 °C. In certain embodiments, Form I of the compound of formula (I) has a DSC thermogram substantially the same as shown in FIG.20. [127] In certain embodiments, Form I of the compound of formula (I) exhibits a change in mass of less than or equal to about 3% wt (weight) when varying the relative humidity between 0% and about 80%, when measured at 25 °C. The mass change exhibited by Form I Attorney Docket No. SLU-030WO of the compound of formula (I) as a function of humidity can be determined, for example, using Dynamic Vapor Sorption (DVS). In certain embodiments, Form I of the compound of formula (I) has a water sorption isotherm, when measured at 25 °C, substantially the same as shown in FIG.21. [128] In certain embodiments, no detectable weight loss occurs upon heating Form I of the compound of formula (I) from room temperature to about 150 °C. The weight loss exhibited by Form I of the compound of formula (I) upon heating can be determined, for example, using thermogravimetric analysis (TGA). In certain embodiments, Form I of the compound of formula (I) has a TGA thermogram substantially the same as shown in FIG.20. (B) Form III [129] In one aspect, provided herein is Form III of a compound of formula (I). [130] In certain embodiments, Form III of the compound of formula (I) is an anhydrous crystalline form. [131] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.7° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, and about 14.3° 2θ. [132] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.1°, about 19.0°, about 19.3°, about 21.8°, and about 24.9° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, and about 24.7° 2θ. [133] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 29.1°, about 32.3°, Attorney Docket No. SLU-030WO about 32.5°, about 33.1°, and about 34.1° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.8°, about 33.6°, about 33.8°, about 34.3°, and about 34.5° 2θ. [134] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, about 14.3°, about 15.1°, about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.0°, about 19.3°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 21.8°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, about 24.7°, about 24.9°, about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.1°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.3°, about 32.5°, about 32.8°, about 33.1°, about 33.6°, about 33.8°, about 34.1°, about 34.3°, and about 34.5° 2θ. [135] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.7° ± 0.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ± 0.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 12.2° ± 0.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 13.3° ± 0.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ± 0.3° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7° ± 0.3°, 10.9° ± 0.3°, 11.9° ± 0.3°, 12.2° ± 0.3°, 13.3° ± 0.3°, and 14.3° ± 0.3° 2θ. [136] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.1° ± 0.3°, 19.0° ± 0.3°, 19.3° ± 0.3°, 21.8° ± 0.3°, and 24.9° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0° ± 0.3°, 16.2° ± 0.3°, 16.8° ± 0.3°, 18.7° ± 0.3°, 19.9° ± 0.3°, 20.2° ± 0.3°, 21.2° ± 0.3°, 21.5° ± 0.3°, 22.7° ± 0.3°, 23.5° ± 0.3°, 24.0° ± 0.3°, 24.5° ± 0.3°, and 24.7° ± 0.3° 2θ. [137] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1° ± 0.3°, 26.4° ± 0.3°, 26.7° ± 0.3°, 26.9° ± 0.3°, 29.1° ± 0.3°, 32.3° ± 0.3°, 32.5° ± 0.3°, 33.1° ± 0.3°, and 34.1° ± 0.3° 2θ. In certain embodiments, the XRPD pattern Attorney Docket No. SLU-030WO further comprises one or more peaks selected from 27.7° ± 0.3°, 28.3° ± 0.3°, 28.6° ± 0.3°, 28.8° ± 0.3°, 29.6° ± 0.3°, 30.3° ± 0.3°, 30.6° ± 0.3°, 31.0° ± 0.3°, 31.4° ± 0.3°, 32.8° ± 0.3°, 33.6° ± 0.3°, 33.8° ± 0.3°, 34.3° ± 0.3°, and 34.5° ± 0.3° 2θ. [138] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7° ± 0.3°, 10.9° ± 0.3°, 11.9° ± 0.3°, 12.2° ± 0.3°, 13.3° ± 0.3°, 14.3° ± 0.3°, 15.1° ± 0.3°, 16.0° ± 0.3°, 16.2° ± 0.3°, 16.8° ± 0.3°, 18.7° ± 0.3°, 19.0° ± 0.3°, 19.3° ± 0.3°, 19.9° ± 0.3°, 20.2° ± 0.3°, 21.2° ± 0.3°, 21.5° ± 0.3°, 21.8° ± 0.3°, 22.7° ± 0.3°, 23.5° ± 0.3°, 24.0° ± 0.3°, 24.5° ± 0.3°, 24.7° ± 0.3°, 24.9° ± 0.3°, 26.1° ± 0.3°, 26.4° ± 0.3°, 26.7° ± 0.3°, 26.9° ± 0.3°, 27.7° ± 0.3°, 28.3° ± 0.3°, 28.6° ± 0.3°, 28.8° ± 0.3°, 29.1° ± 0.3°, 29.6° ± 0.3°, 30.3° ± 0.3°, 30.6° ± 0.3°, 31.0° ± 0.3°, 31.4° ± 0.3°, 32.3° ± 0.3°, 32.5° ± 0.3°, 32.8° ± 0.3°, 33.1° ± 0.3°, 33.6° ± 0.3°, 33.8° ± 0.3°, 34.1° ± 0.3°, 34.3° ± 0.3°, and 34.5° ± 0.3° 2θ. [139] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.7° ± 0.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ± 0.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 11.9° ± 0.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 12.2° ± 0.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 13.3° ± 0.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ± 0.2° 2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7° ± 0.2°, 10.9° ± 0.2°, 11.9° ± 0.2°, 12.2° ± 0.2°, 13.3° ± 0.2°, and 14.3° ± 0.2° 2θ. [140] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.1° ± 0.2°, 19.0° ± 0.2°, 19.3° ± 0.2°, 21.8° ± 0.2°, and 24.9° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0° ± 0.2°, 16.2° ± 0.2°, 16.8° ± 0.2°, 18.7° ± 0.2°, 19.9° ± 0.2°, 20.2° ± 0.2°, 21.2° ± 0.2°, 21.5° ± 0.2°, 22.7° ± 0.2°, 23.5° ± 0.2°, 24.0° ± 0.2°, 24.5° ± 0.2°, and 24.7° ± 0.2° 2θ. [141] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1° ± 0.2°, 26.4° ± 0.2°, 26.7° ± 0.2°, 26.9° ± 0.2°, 29.1° ± 0.2°, 32.3° ± 0.2°, 32.5° ± 0.2°, 33.1° ± 0.2°, and 34.1° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 27.7° ± 0.2°, 28.3° ± 0.2°, 28.6° ± 0.2°, Attorney Docket No. SLU-030WO 28.8° ± 0.2°, 29.6° ± 0.2°, 30.3° ± 0.2°, 30.6° ± 0.2°, 31.0° ± 0.2°, 31.4° ± 0.2°, 32.8° ± 0.2°, 33.6° ± 0.2°, 33.8° ± 0.2°, 34.3° ± 0.2°, and 34.5° ± 0.2° 2θ. [142] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7° ± 0.2°, 10.9° ± 0.2°, 11.9° ± 0.2°, 12.2° ± 0.2°, 13.3° ± 0.2°, 14.3° ± 0.2°, 15.1° ± 0.2°, 16.0° ± 0.2°, 16.2° ± 0.2°, 16.8° ± 0.2°, 18.7° ± 0.2°, 19.0° ± 0.2°, 19.3° ± 0.2°, 19.9° ± 0.2°, 20.2° ± 0.2°, 21.2° ± 0.2°, 21.5° ± 0.2°, 21.8° ± 0.2°, 22.7° ± 0.2°, 23.5° ± 0.2°, 24.0° ± 0.2°, 24.5° ± 0.2°, 24.7° ± 0.2°, 24.9° ± 0.2°, 26.1° ± 0.2°, 26.4° ± 0.2°, 26.7° ± 0.2°, 26.9° ± 0.2°, 27.7° ± 0.2°, 28.3° ± 0.2°, 28.6° ± 0.2°, 28.8° ± 0.2°, 29.1° ± 0.2°, 29.6° ± 0.2°, 30.3° ± 0.2°, 30.6° ± 0.2°, 31.0° ± 0.2°, 31.4° ± 0.2°, 32.3° ± 0.2°, 32.5° ± 0.2°, 32.8° ± 0.2°, 33.1° ± 0.2°, 33.6° ± 0.2°, 33.8° ± 0.2°, 34.1° ± 0.2°, 34.3° ± 0.2°, and 34.5° ± 0.2° 2θ. [143] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 13. [144] In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. [145] In certain embodiments, Form III of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form III of the compound of formula (I) exists in a monoclinic crystal system and has a P121/n1 space group. In certain embodiments, Form III of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 2. Table 2 – Unit Cell Parameters of Form III of the Compound of Formula (I) a [Å] 8.6673(9) )
Figure imgf000027_0001
Attorney Docket No. SLU-030WO (C) Form X [146] In one aspect, provided herein is Form X of a compound of formula (I). [147] In certain embodiments, Form X of the compound of formula (I) is an anhydrous crystalline form. [148] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.6° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.0° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.5° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.6°, about 10.9°, about 12.0°, about 14.1°, and about 14.5° 2θ. [149] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.1°, about 21.9°, and about 24.1° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 17.5°, about 18.0°, about 18.8°, about 19.7°, about 20.7°, about 21.2°, about 21.6°, about 22.3°, about 23.3°, and about 24.6° 2θ. [150] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 27.3°, about 29.0°, about 29.2°, about 30.8°, and about 31.1° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.8°, about 26.4°, about 28.7°, about 30.6°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2θ. [151] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.6°, about 10.9°, about 12.0°, about 14.1°, about 14.5°, about 15.3°, about 17.5°, about 18.0°, about 18.8°, about 19.1°, about 19.7°, about 20.7°, about 21.2°, about 21.6°, about 21.9°, about 22.3°, about 23.3°, about 24.1°, about 24.6°, about 25.2°, about 25.8°, about 26.4°, about 27.3°, about 28.7°, about 29.0°, about 29.2°, about 30.6°, about 30.8°, about 31.1°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2θ. [152] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 10.6° ± 0.3° 2θ. In certain embodiments, Form X of the compound of Attorney Docket No. SLU-030WO formula (I) has an XRPD pattern comprising a peak at 10.9° ± 0.3° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 12.0° ± 0.3° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.3° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 14.5° ± 0.3° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ± 0.3°, 10.9° ± 0.3°, 12.0° ± 0.3°, 14.1° ± 0.3°, and 14.5° ± 0.3° 2θ. [153] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.3°, 19.1° ± 0.3°, 21.9° ± 0.3°, and 24.1° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.5° ± 0.3°, 18.0° ± 0.3°, 18.8° ± 0.3°, 19.7° ± 0.3°, 20.7° ± 0.3°, 21.2° ± 0.3°, 21.6° ± 0.3°, 22.3° ± 0.3°, 23.3° ± 0.3°, and 24.6° ± 0.3° 2θ. [154] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2° ± 0.3°, 27.3° ± 0.3°, 29.0° ± 0.3°, 29.2° ± 0.3°, 30.8° ± 0.3°, and 31.1° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.8° ± 0.3°, 26.4° ± 0.3°, 28.7° ± 0.3°, 30.6° ± 0.3°, 32.4° ± 0.3°, 33.0° ± 0.3°, 33.5° ± 0.3°, 33.9° ± 0.3°, and 34.7° ± 0.3° 2θ. [155] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ± 0.3°, 10.9° ± 0.3°, 12.0° ± 0.3°, 14.1° ± 0.3°, 14.5° ± 0.3°, 15.3° ± 0.3°, 17.5° ± 0.3°, 18.0° ± 0.3°, 18.8° ± 0.3°, 19.1° ± 0.3°, 19.7° ± 0.3°, 20.7° ± 0.3°, 21.2° ± 0.3°, 21.6° ± 0.3°, 21.9° ± 0.3°, 22.3° ± 0.3°, 23.3° ± 0.3°, 24.1° ± 0.3°, 24.6° ± 0.3°, 25.2° ± 0.3°, 25.8° ± 0.3°, 26.4° ± 0.3°, 27.3° ± 0.3°, 28.7° ± 0.3°, 29.0° ± 0.3°, 29.2° ± 0.3°, 30.6° ± 0.3°, 30.8° ± 0.3°, 31.1° ± 0.3°, 32.4° ± 0.3°, 33.0° ± 0.3°, 33.5° ± 0.3°, 33.9° ± 0.3°, and 34.7° ± 0.3° 2θ. [156] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 10.6° ± 0.2° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 10.9° ± 0.2° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 12.0° ± 0.2° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.2° 2θ. In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising a peak at 14.5° ± 0.2° 2θ. In Attorney Docket No. SLU-030WO certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ± 0.2°, 10.9° ± 0.2°, 12.0° ± 0.2°, 14.1° ± 0.2°, and 14.5° ± 0.2° 2θ. [157] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.2°, 19.1° ± 0.2°, 21.9° ± 0.2°, and 24.1° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.5° ± 0.2°, 18.0° ± 0.2°, 18.8° ± 0.2°, 19.7° ± 0.2°, 20.7° ± 0.2°, 21.2° ± 0.2°, 21.6° ± 0.2°, 22.3° ± 0.2°, 23.3° ± 0.2°, and 24.6° ± 0.2° 2θ. [158] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2° ± 0.2°, 27.3° ± 0.2°, 29.0° ± 0.2°, 29.2° ± 0.2°, 30.8° ± 0.2°, and 31.1° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.8° ± 0.2°, 26.4° ± 0.2°, 28.7° ± 0.2°, 30.6° ± 0.2°, 32.4° ± 0.2°, 33.0° ± 0.2°, 33.5° ± 0.2°, 33.9° ± 0.2°, and 34.7° ± 0.2° 2θ. [159] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising peaks at 10.6° ± 0.2°, 10.9° ± 0.2°, 12.0° ± 0.2°, 14.1° ± 0.2°, 14.5° ± 0.2°, 15.3° ± 0.2°, 17.5° ± 0.2°, 18.0° ± 0.2°, 18.8° ± 0.2°, 19.1° ± 0.2°, 19.7° ± 0.2°, 20.7° ± 0.2°, 21.2° ± 0.2°, 21.6° ± 0.2°, 21.9° ± 0.2°, 22.3° ± 0.2°, 23.3° ± 0.2°, 24.1° ± 0.2°, 24.6° ± 0.2°, 25.2° ± 0.2°, 25.8° ± 0.2°, 26.4° ± 0.2°, 27.3° ± 0.2°, 28.7° ± 0.2°, 29.0° ± 0.2°, 29.2° ± 0.2°, 30.6° ± 0.2°, 30.8° ± 0.2°, 31.1° ± 0.2°, 32.4° ± 0.2°, 33.0° ± 0.2°, 33.5° ± 0.2°, 33.9° ± 0.2°, and 34.7° ± 0.2° 2θ. [160] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 20. [161] In certain embodiments, Form X of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.10. [162] In certain embodiments, Form X of the compound of formula (I) has a DSC thermogram comprising an endotherm with a peak onset at about 235.8 °C. In certain embodiments, Form X of the compound of formula (I) has a DSC thermogram comprising an endotherm with a peak onset at about 281.9 °C. In certain embodiments, Form X of the compound of formula (I) has a DSC thermogram comprising one or more endotherms with peak onsets at about 235.8 °C and about 281.9 °C. In certain embodiments, Form X of the compound of formula (I) has a DSC thermogram substantially the same as shown in FIG.22. Attorney Docket No. SLU-030WO [163] In certain embodiments, Form X of the compound of formula (I) exhibits a change in mass of less than or equal to about 3% wt when varying the relative humidity between 0% and about 80%, when measured at 25 °C. The mass change exhibited by Form X of the compound of formula (I) as a function of humidity can be determined, for example, using DVS. In certain embodiments, Form X of the compound of formula (I) has a water sorption isotherm, when measured at 25 °C, substantially the same as shown in FIG.23. [164] In certain embodiments, no detectable weight loss occurs upon heating Form X of the compound of formula (I) from room temperature to about 150 °C. The weight loss exhibited by Form X of the compound of formula (I) upon heating can be determined, for example, using TGA. In certain embodiments, Form X of the compound of formula (I) has a TGA thermogram substantially the same as shown in FIG.22. (2) Crystalline Hydrate of a Compound of Formula (I) [165] In one aspect, provided herein are crystalline hydrate forms of a compound of formula (I). In certain embodiments, the crystalline hydrate of the compound of formula (I) is a crystalline monohydrate. (A) Form II [166] In one aspect, provided herein is Form II of a compound of formula (I). [167] In certain embodiments, Form II of the compound of formula (I) is a crystalline hydrate. In certain embodiments, Form II of the compound of formula (I) is a crystalline monohydrate. [168] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 6.9° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.2° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.7° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.9° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at about 6.9°, about 11.2°, about 11.7°, about 13.9°, and about 14.3° 2θ. Attorney Docket No. SLU-030WO [169] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 15.5°, about 17.4°, about 20.9°, about 22.3°, and about 23.6° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 17.9°, about 19.7°, about 21.4°, about 22.8°, about 23.8°, and about 24.9° 2θ. [170] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, and about 28.8° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 28.6°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2θ. [171] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at about 6.9°, about 11.2°, about 11.7°, about 13.9°, about 14.3°, about 15.3°, about 15.5°, about 17.4°, about 17.9°, about 19.7°, about 20.9°, about 21.4°, about 22.3°, about 22.8°, about 23.6°, about 23.8°, about 24.9°, about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, about 28.6°, about 28.8°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2θ. [172] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 6.9° ± 0.3° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 11.2° ± 0.3° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 11.7° ± 0.3° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ± 0.3° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ± 0.3° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9° ± 0.3°, 11.2° ± 0.3°, 11.7° ± 0.3°, 13.9° ± 0.3°, and 14.3° ± 0.3° 2θ. [173] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.3°, 15.5° ± 0.3°, 17.4° ± 0.3°, 20.9° ± 0.3°, 22.3° ± 0.3°, and 23.6° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.9° ± 0.3°, 19.7° ± 0.3°, 21.4° ± 0.3°, 22.8° ± 0.3°, 23.8° ± 0.3°, and 24.9° ± 0.3° 2θ. [174] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2° ± 0.3°, 25.5° ± 0.3°, 25.7° ± 0.3°, 26.4° ± 0.3°, 27.0° ± 0.3°, 27.5° ± 0.3°, Attorney Docket No. SLU-030WO 28.1° ± 0.3°, 28.2° ± 0.3°, and 28.8° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 28.6° ± 0.3°, 29.2° ± 0.3°, 29.9° ± 0.3°, 31.3° ± 0.3°, 31.4° ± 0.3°, 31.9° ± 0.3°, 32.6° ± 0.3°, 33.7° ± 0.3°, and 34.3° ± 0.3° 2θ. [175] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9° ± 0.3°, 11.2° ± 0.3°, 11.7° ± 0.3°, 13.9° ± 0.3°, 14.3° ± 0.3°, 15.3° ± 0.3°, 15.5° ± 0.3°, 17.4° ± 0.3°, 17.9° ± 0.3°, 19.7° ± 0.3°, 20.9° ± 0.3°, 21.4° ± 0.3°, 22.3° ± 0.3°, 22.8° ± 0.3°, 23.6° ± 0.3°, 23.8° ± 0.3°, 24.9° ± 0.3°, 25.2° ± 0.3°, 25.5° ± 0.3°, 25.7° ± 0.3°, 26.4° ± 0.3°, 27.0° ± 0.3°, 27.5° ± 0.3°, 28.1° ± 0.3°, 28.2° ± 0.3°, 28.6° ± 0.3°, 28.8° ± 0.3°, 29.2° ± 0.3°, 29.9° ± 0.3°, 31.3° ± 0.3°, 31.4° ± 0.3°, 31.9° ± 0.3°, 32.6° ± 0.3°, 33.7° ± 0.3°, and 34.3° ± 0.3° 2θ. [176] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 6.9° ± 0.2° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 11.2° ± 0.2° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 11.7° ± 0.2° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ± 0.2° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ± 0.2° 2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9° ± 0.2°, 11.2° ± 0.2°, 11.7° ± 0.2°, 13.9° ± 0.2°, and 14.3° ± 0.2° 2θ. [177] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3° ± 0.2°, 15.5° ± 0.2°, 17.4° ± 0.2°, 20.9° ± 0.2°, 22.3° ± 0.2°, and 23.6° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.9° ± 0.2°, 19.7° ± 0.2°, 21.4° ± 0.2°, 22.8° ± 0.2°, 23.8° ± 0.2°, and 24.9° ± 0.2° 2θ. [178] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2° ± 0.2°, 25.5° ± 0.2°, 25.7° ± 0.2°, 26.4° ± 0.2°, 27.0° ± 0.2°, 27.5° ± 0.2°, 28.1° ± 0.2°, 28.2° ± 0.2°, and 28.8° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 28.6° ± 0.2°, 29.2° ± 0.2°, 29.9° ± 0.2°, 31.3° ± 0.2°, 31.4° ± 0.2°, 31.9° ± 0.2°, 32.6° ± 0.2°, 33.7° ± 0.2°, and 34.3° ± 0.2° 2θ. [179] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9° ± 0.2°, 11.2° ± 0.2°, 11.7° ± 0.2°, 13.9° ± 0.2°, 14.3° ± 0.2°, 15.3° ± 0.2°, 15.5° ± 0.2°, 17.4° ± 0.2°, 17.9° ± 0.2°, 19.7° ± 0.2°, 20.9° ± 0.2°, 21.4° ± 0.2°, 22.3° ± Attorney Docket No. SLU-030WO 0.2°, 22.8° ± 0.2°, 23.6° ± 0.2°, 23.8° ± 0.2°, 24.9° ± 0.2°, 25.2° ± 0.2°, 25.5° ± 0.2°, 25.7° ± 0.2°, 26.4° ± 0.2°, 27.0° ± 0.2°, 27.5° ± 0.2°, 28.1° ± 0.2°, 28.2° ± 0.2°, 28.6° ± 0.2°, 28.8° ± 0.2°, 29.2° ± 0.2°, 29.9° ± 0.2°, 31.3° ± 0.2°, 31.4° ± 0.2°, 31.9° ± 0.2°, 32.6° ± 0.2°, 33.7° ± 0.2°, and 34.3° ± 0.2° 2θ. [180] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 12. [181] In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.2. [182] In certain embodiments, Form II of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form II of the compound of formula (I) exists in an orthorhombic crystal system and has a C2221 space group. In certain embodiments, Form II of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 3. Table 3 – Unit Cell Parameters of Form II of the Compound of Formula (I) a [Å] 6.9834(2) b [Å] 157599(6) )
Figure imgf000034_0001
(3) Crystalline Solvates of a Compound of Formula (I) [183] In one aspect, provided herein are crystalline solvate forms of a compound of formula (I). In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetonitrile solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetic acid solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an ethanol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is a methanol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an ethylene glycol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetone solvate. Attorney Docket No. SLU-030WO [184] In certain embodiments, the crystalline solvate of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, the crystalline solvate of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group. [185] In certain embodiments, the crystalline solvate of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, the crystalline solvate of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. (A) Form IV [186] In one aspect, provided herein is Form IV of a compound of formula (I). [187] In certain embodiments, Form IV of the compound of formula (I) is a crystalline acetonitrile solvate. In certain embodiments, Form IV of the compound of formula (I) is a crystalline mono-acetonitrile solvate. [188] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at about 7.2° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at about 9.6° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.8° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.1° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.5° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at about 7.2°, about 9.6°, about 10.8°, about 13.1°, and about 14.5° 2θ. [189] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.8°, about 16.6°, about 18.2°, about 19.2°, and about 21.6° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 20.1°, about 21.9°, about 22.8°, and about 23.0° 2θ. [190] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.1°, about 25.3°, about 26.0°, about 26.3°, about 27.1°, about 27.6°, about 28.6°, about 31.8°, about 32.7°, and about 33.7° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 29.0°, about 29.2°, about 29.9°, about 31.2°, about 32.0°, about 32.4°, about 33.5°, and about 34.1° 2θ. Attorney Docket No. SLU-030WO [191] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at about 7.2°, about 9.6°, about 10.8°, about 13.1°, about 14.5°, about 15.8°, about 16.6°, about 18.2°, about 19.2°, about 20.1°, about 21.6°, about 21.9°, about 22.8°, about 23.0°, about 25.1°, about 25.3°, about 26.0°, about 26.3°, about 27.1°, about 27.6°, about 28.6°, about 29.0°, about 29.2°, about 29.9°, about 31.2°, about 31.8°, about 32.0°, about 32.4°, about 32.7°, about 33.5°, about 33.7°, and about 34.1° 2θ. [192] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 7.2° ± 0.3° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 9.6° ± 0.3° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 10.8° ± 0.3° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 13.1° ± 0.3° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 14.5° ± 0.3° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at 7.2° ± 0.3°, 9.6° ± 0.3°, 10.8° ± 0.3°, 13.1° ± 0.3°, and 14.5° ± 0.3° 2θ. [193] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.8° ± 0.3°, 16.6° ± 0.3°, 18.2° ± 0.3°, 19.2° ± 0.3°, and 21.6° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 20.1° ± 0.3°, 21.9° ± 0.3°, 22.8° ± 0.3°, and 23.0° ± 0.3° 2θ. [194] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1° ± 0.3°, 25.3° ± 0.3°, 26.0° ± 0.3°, 26.3° ± 0.3°, 27.1° ± 0.3°, 27.6° ± 0.3°, 28.6° ± 0.3°, 31.8° ± 0.3°, 32.7° ± 0.3°, and 33.7° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 29.0° ± 0.3°, 29.2° ± 0.3°, 29.9° ± 0.3°, 31.2° ± 0.3°, 32.0° ± 0.3°, 32.4° ± 0.3°, 33.5° ± 0.3°, and 34.1° ± 0.3° 2θ. [195] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at 7.2° ± 0.3°, 9.6° ± 0.3°, 10.8° ± 0.3°, 13.1° ± 0.3°, 14.5° ± 0.3°, 15.8° ± 0.3°, 16.6° ± 0.3°, 18.2° ± 0.3°, 19.2° ± 0.3°, 20.1° ± 0.3°, 21.6° ± 0.3°, 21.9° ± 0.3°, 22.8° ± 0.3°, 23.0° ± 0.3°, 25.1° ± 0.3°, 25.3° ± 0.3°, 26.0° ± 0.3°, 26.3° ± 0.3°, 27.1° ± 0.3°, 27.6° ± 0.3°, 28.6° ± 0.3°, 29.0° ± 0.3°, 29.2° ± 0.3°, 29.9° ± 0.3°, 31.2° ± 0.3°, 31.8° ± 0.3°, 32.0° ± 0.3°, 32.4° ± 0.3°, 32.7° ± 0.3°, 33.5° ± 0.3°, 33.7° ± 0.3°, and 34.1° ± 0.3° 2θ. Attorney Docket No. SLU-030WO [196] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 7.2° ± 0.2° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 9.6° ± 0.2° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 10.8° ± 0.2° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 13.1° ± 0.2° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising a peak at 14.5° ± 0.2° 2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at 7.2° ± 0.2°, 9.6° ± 0.2°, 10.8° ± 0.2°, 13.1° ± 0.2°, and 14.5° ± 0.2° 2θ. [197] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.8° ± 0.2°, 16.6° ± 0.2°, 18.2° ± 0.2°, 19.2° ± 0.2°, and 21.6° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 20.1° ± 0.2°, 21.9° ± 0.2°, 22.8° ± 0.2°, and 23.0° ± 0.2° 2θ. [198] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1° ± 0.2°, 25.3° ± 0.2°, 26.0° ± 0.2°, 26.3° ± 0.2°, 27.1° ± 0.2°, 27.6° ± 0.2°, 28.6° ± 0.2°, 31.8° ± 0.2°, 32.7° ± 0.2°, and 33.7° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 29.0° ± 0.2°, 29.2° ± 0.2°, 29.9° ± 0.2°, 31.2° ± 0.2°, 32.0° ± 0.2°, 32.4° ± 0.2°, 33.5° ± 0.2°, and 34.1° ± 0.2° 2θ. [199] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at 7.2° ± 0.2°, 9.6° ± 0.2°, 10.8° ± 0.2°, 13.1° ± 0.2°, 14.5° ± 0.2°, 15.8° ± 0.2°, 16.6° ± 0.2°, 18.2° ± 0.2°, 19.2° ± 0.2°, 20.1° ± 0.2°, 21.6° ± 0.2°, 21.9° ± 0.2°, 22.8° ± 0.2°, 23.0° ± 0.2°, 25.1° ± 0.2°, 25.3° ± 0.2°, 26.0° ± 0.2°, 26.3° ± 0.2°, 27.1° ± 0.2°, 27.6° ± 0.2°, 28.6° ± 0.2°, 29.0° ± 0.2°, 29.2° ± 0.2°, 29.9° ± 0.2°, 31.2° ± 0.2°, 31.8° ± 0.2°, 32.0° ± 0.2°, 32.4° ± 0.2°, 32.7° ± 0.2°, 33.5° ± 0.2°, 33.7° ± 0.2°, and 34.1° ± 0.2° 2θ. [200] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 14. [201] In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.4. [202] In certain embodiments, Form IV of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form IV of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. In certain embodiments, Attorney Docket No. SLU-030WO Form IV of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 4. Table 4 – Unit Cell Parameters of Form IV of the Compound of Formula (I) a [Å] 9.411(3) b [Å] 7.040(2) ) (B) Form V
Figure imgf000038_0001
[203] In one aspect, provided herein is Form V of a compound of formula (I). [204] In certain embodiments, Form V of the compound of formula (I) is a crystalline acetic acid solvate. In certain embodiments, Form V of the compound of formula (I) is a crystalline bis-acetic acid solvate. [205] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 7.6° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 8.0° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 8.4° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.9° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 15.0° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 7.6°, about 8.0°, about 8.4°, about 13.3°, about 13.9°, and about 15.0° 2θ. [206] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.2°, about 19.0°, about 19.5°, about 20.2°, about 20.7°, and about 24.0° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected Attorney Docket No. SLU-030WO from about 15.4°, about 16.1°, about 22.1°, about 22.5°, about 23.1°, about 24.4°, and about 24.7° 2θ. [207] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.4°, about 25.9°, about 26.5°, about 27.1°, about 27.3°, about 29.6°, about 29.9°, about 30.1°, about 30.6°, and about 30.7° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.6°, about 26.7°, about 27.6°, about 28.5°, about 29.4°, about 30.3°, about 31.1°, about 31.4°, about 32.2°, about 32.8°, about 33.1°, about 33.4°, about 33.6°, about 34.1°, about 34.3°, about 34.6°, and about 35.0° 2θ. [208] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at about 7.6°, about 8.0°, about 8.4°, about 13.3°, about 13.9°, about 15.0°, about 15.2°, about 15.4°, about 16.1°, about 19.0°, about 19.5°, about 20.2°, about 20.7°, about 22.1°, about 22.5°, about 23.1°, about 24.0°, about 24.4°, and about 24.7°, about 25.4°, about 25.6°, about 25.9°, about 26.5°, about 26.7°, about 27.1°, about 27.3°, about 27.6°, about 28.5°, about 29.4°, about 29.6°, about 29.9°, about 30.1°, about 30.3°, about 30.6°, about 30.7°, about 31.1°, about 31.4°, about 32.2°, about 32.8°, about 33.1°, about 33.4°, about 33.6°, about 34.1°, about 34.3°, about 34.6°, and about 35.0° 2θ. [209] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 7.6° ± 0.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 8.0° ± 0.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 8.4° ± 0.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 13.3° ± 0.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ± 0.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 15.0° ± 0.3° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 7.6° ± 0.3°, 8.0° ± 0.3°, 8.4° ± 0.3°, 13.3° ± 0.3°, 13.9° ± 0.3°, and 15.0° ± 0.3° 2θ. [210] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2° ± 0.3°, 19.0° ± 0.3°, 19.5° ± 0.3°, 20.2° ± 0.3°, 20.7° ± 0.3°, and 24.0° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks Attorney Docket No. SLU-030WO selected from 15.4° ± 0.3°, 16.1° ± 0.3°, 22.1° ± 0.3°, 22.5° ± 0.3°, 23.1° ± 0.3°, 24.4° ± 0.3°, and 24.7° ± 0.3° 2θ. [211] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.4° ± 0.3°, 25.9° ± 0.3°, 26.5° ± 0.3°, 27.1° ± 0.3°, 27.3° ± 0.3°, 29.6° ± 0.3°, 29.9° ± 0.3°, 30.1° ± 0.3°, 30.6° ± 0.3°, and 30.7° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6° ± 0.3°, 26.7° ± 0.3°, 27.6° ± 0.3°, 28.5° ± 0.3°, 29.4° ± 0.3°, 30.3° ± 0.3°, 31.1° ± 0.3°, 31.4° ± 0.3°, 32.2° ± 0.3°, 32.8° ± 0.3°, 33.1° ± 0.3°, 33.4° ± 0.3°, 33.6° ± 0.3°, 34.1° ± 0.3°, 34.3° ± 0.3°, 34.6° ± 0.3°, and 35.0° ± 0.3° 2θ. [212] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 7.6° ± 0.3°, 8.0° ± 0.3°, 8.4° ± 0.3°, 13.3° ± 0.3°, 13.9° ± 0.3°, 15.0° ± 0.3°, 15.2° ± 0.3°, 15.4° ± 0.3°, 16.1° ± 0.3°, 19.0° ± 0.3°, 19.5° ± 0.3°, 20.2° ± 0.3°, 20.7° ± 0.3°, 22.1° ± 0.3°, 22.5° ± 0.3°, 23.1° ± 0.3°, 24.0° ± 0.3°, 24.4° ± 0.3°, and 24.7° ± 0.3°, 25.4° ± 0.3°, 25.6° ± 0.3°, 25.9° ± 0.3°, 26.5° ± 0.3°, 26.7° ± 0.3°, 27.1° ± 0.3°, 27.3° ± 0.3°, 27.6° ± 0.3°, 28.5° ± 0.3°, 29.4° ± 0.3°, 29.6° ± 0.3°, 29.9° ± 0.3°, 30.1° ± 0.3°, 30.3° ± 0.3°, 30.6° ± 0.3°, 30.7° ± 0.3°, 31.1° ± 0.3°, 31.4° ± 0.3°, 32.2° ± 0.3°, 32.8° ± 0.3°, 33.1° ± 0.3°, 33.4° ± 0.3°, 33.6° ± 0.3°, 34.1° ± 0.3°, 34.3° ± 0.3°, 34.6° ± 0.3°, and 35.0° ± 0.3° 2θ. [213] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 7.6° ± 0.2° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 8.0° ± 0.2° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 8.4° ± 0.2° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 13.3° ± 0.2° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ± 0.2° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 15.0° ± 0.2° 2θ. In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 7.6° ± 0.2°, 8.0° ± 0.2°, 8.4° ± 0.2°, 13.3° ± 0.2°, 13.9° ± 0.2°, and 15.0° ± 0.2° 2θ. [214] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2° ± 0.2°, 19.0° ± 0.2°, 19.5° ± 0.2°, 20.2° ± 0.2°, 20.7° ± 0.2°, and 24.0° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks Attorney Docket No. SLU-030WO selected from 15.4° ± 0.2°, 16.1° ± 0.2°, 22.1° ± 0.2°, 22.5° ± 0.2°, 23.1° ± 0.2°, 24.4° ± 0.2°, and 24.7° ± 0.2° 2θ. [215] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.4° ± 0.2°, 25.9° ± 0.2°, 26.5° ± 0.2°, 27.1° ± 0.2°, 27.3° ± 0.2°, 29.6° ± 0.2°, 29.9° ± 0.2°, 30.1° ± 0.2°, 30.6° ± 0.2°, and 30.7° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6° ± 0.2°, 26.7° ± 0.2°, 27.6° ± 0.2°, 28.5° ± 0.2°, 29.4° ± 0.2°, 30.3° ± 0.2°, 31.1° ± 0.2°, 31.4° ± 0.2°, 32.2° ± 0.2°, 32.8° ± 0.2°, 33.1° ± 0.2°, 33.4° ± 0.2°, 33.6° ± 0.2°, 34.1° ± 0.2°, 34.3° ± 0.2°, 34.6° ± 0.2°, and 35.0° ± 0.2° 2θ. [216] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising a peak at 7.6° ± 0.2°, 8.0° ± 0.2°, 8.4° ± 0.2°, 13.3° ± 0.2°, 13.9° ± 0.2°, 15.0° ± 0.2°, 15.2° ± 0.2°, 15.4° ± 0.2°, 16.1° ± 0.2°, 19.0° ± 0.2°, 19.5° ± 0.2°, 20.2° ± 0.2°, 20.7° ± 0.2°, 22.1° ± 0.2°, 22.5° ± 0.2°, 23.1° ± 0.2°, 24.0° ± 0.2°, 24.4° ± 0.2°, and 24.7° ± 0.2°, 25.4° ± 0.2°, 25.6° ± 0.2°, 25.9° ± 0.2°, 26.5° ± 0.2°, 26.7° ± 0.2°, 27.1° ± 0.2°, 27.3° ± 0.2°, 27.6° ± 0.2°, 28.5° ± 0.2°, 29.4° ± 0.2°, 29.6° ± 0.2°, 29.9° ± 0.2°, 30.1° ± 0.2°, 30.3° ± 0.2°, 30.6° ± 0.2°, 30.7° ± 0.2°, 31.1° ± 0.2°, 31.4° ± 0.2°, 32.2° ± 0.2°, 32.8° ± 0.2°, 33.1° ± 0.2°, 33.4° ± 0.2°, 33.6° ± 0.2°, 34.1° ± 0.2°, 34.3° ± 0.2°, 34.6° ± 0.2°, and 35.0° ± 0.2° 2θ. [217] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 15. [218] In certain embodiments, Form V of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.5. [219] In certain embodiments, Form V of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form V of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. In certain embodiments, Form V of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 5.
Attorney Docket No. SLU-030WO Table 5 – Unit Cell Parameters of Form V of the Compound of Formula (I) a [Å] 12.1628(12) b [Å] 6.8632(6) ) (C) Form VI
Figure imgf000042_0001
[220] In one aspect, provided herein is Form VI of a compound of formula (I). [221] In certain embodiments, Form VI of the compound of formula (I) is a crystalline ethanol solvate. In certain embodiments, Form VI of the compound of formula (I) is a crystalline mono-ethanol solvate. [222] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at about 8.5° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at about 9.0° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.5° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.4° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at about 8.5°, about 9.0°, about 11.5°, about 14.1°, and about 14.4° 2θ. [223] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.1°, about 17.4°, about 16.1°, about 18.8°, about 21.3°, about 22.0°, about 22.7°, and about 24.4° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 18.0°, about 20.3°, about 20.4°, about 23.3°, about 23.8°, and about 24.2° 2θ. [224] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.5°, about 25.7°, about 26.3°, about 28.4°, about 29.5°, about 29.6°, about 30.5°, and about 31.1° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.5°, about 27.3°, about 28.0°, about Attorney Docket No. SLU-030WO 28.9°, about 29.2°, about 30.1°, about 31.5°, about 31.7°, about 32.2°, about 32.6°, about 33.4°, about 34.3°, about 34.4°, and about 34.7° 2θ. [225] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at about 8.5°, about 9.0°, about 11.5°, about 14.1°, about 14.4°, about 16.1°, about 17.4°, about 16.1°, about 18.0°, about 18.8°, about 20.3°, about 20.4°, about 21.3°, about 22.0°, about 22.7°, 23.3°, about 23.8°, about 24.2°, about 24.4°, about 25.5°, about 25.7°, about 26.3°, about 26.5°, about 27.3°, about 28.0°, about 28.4°, about 28.9°, about 29.2°, about 29.5°, about 29.6°, about 30.1°, about 30.5°, about 31.1°, about 31.5°, about 31.7°, about 32.2°, about 32.6°, about 33.4°, about 34.3°, about 34.4°, and about 34.7° 2θ. [226] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 8.5° ± 0.3° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 9.0° ± 0.3° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 11.5° ± 0.3° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.3° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 14.4° ± 0.3° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at 8.5° ± 0.3°, 9.0° ± 0.3°, 11.5° ± 0.3°, 14.1° ± 0.3°, and 14.4° ± 0.3° 2θ. [227] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.1° ± 0.3°, 17.4° ± 0.3°, 16.1° ± 0.3°, 18.8° ± 0.3°, 21.3° ± 0.3°, 22.0° ± 0.3°, 22.7° ± 0.3°, and 24.4° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 18.0° ± 0.3°, 20.3° ± 0.3°, 20.4° ± 0.3°, 23.3° ± 0.3°, 23.8° ± 0.3°, and 24.2° ± 0.3° 2θ. [228] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.5° ± 0.3°, 25.7° ± 0.3°, 26.3° ± 0.3°, 28.4° ± 0.3°, 29.5° ± 0.3°, 29.6° ± 0.3°, 30.5° ± 0.3°, and 31.1° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.5° ± 0.3°, 27.3° ± 0.3°, 28.0° ± 0.3°, 28.9° ± 0.3°, 29.2° ± 0.3°, 30.1° ± 0.3°, 31.5° ± 0.3°, 31.7° ± 0.3°, 32.2° ± 0.3°, 32.6° ± 0.3°, 33.4° ± 0.3°, 34.3° ± 0.3°, 34.4° ± 0.3°, and 34.7° ± 0.3° 2θ. Attorney Docket No. SLU-030WO [229] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at 8.5° ± 0.3°, 9.0° ± 0.3°, 11.5° ± 0.3°, 14.1° ± 0.3°, 14.4° ± 0.3°, 16.1° ± 0.3°, 17.4° ± 0.3°, 16.1° ± 0.3°, 18.0° ± 0.3°, 18.8° ± 0.3°, 20.3° ± 0.3°, 20.4° ± 0.3°, 21.3° ± 0.3°, 22.0° ± 0.3°, 22.7° ± 0.3°, 23.3° ± 0.3°, 23.8° ± 0.3°, 24.2° ± 0.3°, 24.4° ± 0.3°, 25.5° ± 0.3°, 25.7° ± 0.3°, 26.3° ± 0.3°, 26.5° ± 0.3°, 27.3° ± 0.3°, 28.0° ± 0.3°, 28.4° ± 0.3°, 28.9° ± 0.3°, 29.2° ± 0.3°, 29.5° ± 0.3°, 29.6° ± 0.3°, 30.1° ± 0.3°, 30.5° ± 0.3°, 31.1° ± 0.3°, 31.5° ± 0.3°, 31.7° ± 0.3°, 32.2° ± 0.3°, 32.6° ± 0.3°, 33.4° ± 0.3°, 34.3° ± 0.3°, 34.4° ± 0.3°, and 34.7° ± 0.3° 2θ. [230] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 8.5° ± 0.2° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 9.0° ± 0.2° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 11.5° ± 0.2° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 14.1° ± 0.2° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising a peak at 14.4° ± 0.2° 2θ. In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at 8.5° ± 0.2°, 9.0° ± 0.2°, 11.5° ± 0.2°, 14.1° ± 0.2°, and 14.4° ± 0.2° 2θ. [231] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.1° ± 0.2°, 17.4° ± 0.2°, 16.1° ± 0.2°, 18.8° ± 0.2°, 21.3° ± 0.2°, 22.0° ± 0.2°, 22.7° ± 0.2°, and 24.4° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 18.0° ± 0.2°, 20.3° ± 0.2°, 20.4° ± 0.2°, 23.3° ± 0.2°, 23.8° ± 0.2°, and 24.2° ± 0.2° 2θ. [232] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.5° ± 0.2°, 25.7° ± 0.2°, 26.3° ± 0.2°, 28.4° ± 0.2°, 29.5° ± 0.2°, 29.6° ± 0.2°, 30.5° ± 0.2°, and 31.1° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.5° ± 0.2°, 27.3° ± 0.2°, 28.0° ± 0.2°, 28.9° ± 0.2°, 29.2° ± 0.2°, 30.1° ± 0.2°, 31.5° ± 0.2°, 31.7° ± 0.2°, 32.2° ± 0.2°, 32.6° ± 0.2°, 33.4° ± 0.2°, 34.3° ± 0.2°, 34.4° ± 0.2°, and 34.7° ± 0.2° 2θ. [233] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising peaks at 8.5° ± 0.2°, 9.0° ± 0.2°, 11.5° ± 0.2°, 14.1° ± 0.2°, 14.4° ± 0.2°, 16.1° ± 0.2°, 17.4° ± 0.2°, 16.1° ± 0.2°, 18.0° ± 0.2°, 18.8° ± 0.2°, 20.3° ± 0.2°, 20.4° ± 0.2°, Attorney Docket No. SLU-030WO 21.3° ± 0.2°, 22.0° ± 0.2°, 22.7° ± 0.2°, 23.3° ± 0.2°, 23.8° ± 0.2°, 24.2° ± 0.2°, 24.4° ± 0.2°, 25.5° ± 0.2°, 25.7° ± 0.2°, 26.3° ± 0.2°, 26.5° ± 0.2°, 27.3° ± 0.2°, 28.0° ± 0.2°, 28.4° ± 0.2°, 28.9° ± 0.2°, 29.2° ± 0.2°, 29.5° ± 0.2°, 29.6° ± 0.2°, 30.1° ± 0.2°, 30.5° ± 0.2°, 31.1° ± 0.2°, 31.5° ± 0.2°, 31.7° ± 0.2°, 32.2° ± 0.2°, 32.6° ± 0.2°, 33.4° ± 0.2°, 34.3° ± 0.2°, 34.4° ± 0.2°, and 34.7° ± 0.2° 2θ. [234] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 16. [235] In certain embodiments, Form VI of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.6. [236] In certain embodiments, Form VI of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form VI of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. In certain embodiments, Form VI of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 6. Table 6 – Unit Cell Parameters of Form VI of the Compound of Formula (I) a [Å] 9.9450(3) b [Å] 783332 )
Figure imgf000045_0001
(D) Form VII [237] In one aspect, provided herein is Form VII of a compound of formula (I). [238] In certain embodiments, Form VII of the compound of formula (I) is a crystalline methanol solvate. In certain embodiments, Form VII of the compound of formula (I) is a crystalline hemi-methanol solvate. [239] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 4.9° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 8.5° 2θ. In certain Attorney Docket No. SLU-030WO embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 9.5° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 9.8° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.0° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.1° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.8° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.9° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.4° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.6° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.8° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at about 4.9°, about 8.5°, about 9.5°, about 9.8°, about 11.0°, about 12.1°, about 12.8°, about 13.9°, about 14.4°, and about 14.8° 2θ. [240] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.2°, about 16.3°, about 16.5°, about 17.5°, about 18.0°, about 19.0°, about 19.1°, about 20.2°, about 20.4°, about 21.0°, about 21.6°, about 22.5°, about 23.7°, about 24.5°, and about 24.9° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.2°, about 16.9°, about 17.1°, about 19.8°, about 20.7°, about 21.4°, about 22.1°, about 23.1°, about 23.9°, and about 24.3° 2θ. [241] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.1°, about 25.3°, about 25.8°, about 27.1°, about 27.5°, about 27.7°, about 28.4°, about 29.5°, about 29.8°, about 31.0°, and about 34.9° 2θ. In certain
Figure imgf000046_0001
embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.3°, about 26.6°, about 26.7°, about 27.9°, about 28.1°, about 28.7°, about 28.9°, about 29.1°, about 30.2°, about 30.7°, about 31.3°, about 31.6°, about 31.8°, about 32.2°, about 32.6°, about 33.1°, about 33.4°, about 33.8°, about 34.0°, about 34.2°, and about 34.6° 2θ. [242] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising peaks at about 4.9°, about 8.5°, about 9.5°, about 9.8°, about 11.0°, about 12.1°, about 12.8°, about 13.9°, about 14.4°, about 14.8°, about 15.2°, about 16.2°, about Attorney Docket No. SLU-030WO 16.3°, about 16.5°, about 16.9°, about 17.1°, about 17.5°, about 18.0°, about 19.0°, about 19.1°, about 19.8°, about 20.2°, about 20.4°, about 20.7°, about 21.0°, about 21.4°, about 21.6°, about 22.1°, about 22.5°, about 23.1°, about 23.7°, about 23.9°, about 24.3°, about 24.5°, about 24.9°, about 25.1°, about 25.3°, about 25.8°, about 26.3°, about 26.6°, about 26.7°, about 27.1°, about 27.5°, about 27.7°, about 27.9°, about 28.1°, about 28.4°, about 28.7°, about 28.9°, about 29.1°, about 29.5°, about 29.8°, about 30.2°, about 30.7°, about 31.0°, about 31.3°, about 31.6°, about 31.8°, about 32.2°, about 32.6°, about 33.1°, about 33.4°, about 33.8°, about 34.0°, about 34.2°, about 34.6°, and about 34.9° 2θ. [243] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 4.9° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 8.5° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 9.5° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 9.8° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.1° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.8° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.4° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.6° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.8° ± 0.3° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 4.9° ± 0.3°, 8.5° ± 0.3°, 9.5° ± 0.3°, 9.8° ± 0.3°, 11.0° ± 0.3°, 12.1° ± 0.3°, 12.8° ± 0.3°, 13.9° ± 0.3°, 14.4° ± 0.3°, and 14.8° ± 0.3° 2θ. [244] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2° ± 0.3°, 16.3° ± 0.3°, 16.5° ± 0.3°, 17.5° ± 0.3°, 18.0° ± 0.3°, 19.0° ± 0.3°, 19.1° ± 0.3°, 20.2° ± 0.3°, 20.4° ± 0.3°, 21.0° ± 0.3°, 21.6° ± 0.3°, 22.5° ± 0.3°, 23.7° ± 0.3°, 24.5° ± 0.3°, and 24.9° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further Attorney Docket No. SLU-030WO comprises one or more peaks selected from 16.2° ± 0.3°, 16.9° ± 0.3°, 17.1° ± 0.3°, 19.8° ± 0.3°, 20.7° ± 0.3°, 21.4° ± 0.3°, 22.1° ± 0.3°, 23.1° ± 0.3°, 23.9° ± 0.3°, and 24.3° ± 0.3° 2θ. [245] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1° ± 0.3°, 25.3° ± 0.3°, 25.8° ± 0.3°, 27.1° ± 0.3°, 27.5° ± 0.3°, 27.7° ± 0.3°, 28.4° ± 0.3°, 29.5° ± 0.3°, 29.8° ± 0.3°, 31.0° ± 0.3°, and 34.9° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.3° ± 0.3°, 26.6° ± 0.3°, 26.7° ± 0.3°, 27.9° ± 0.3°, 28.1° ± 0.3°, 28.7° ± 0.3°, 28.9° ± 0.3°, 29.1° ± 0.3°, 30.2° ± 0.3°, 30.7° ± 0.3°, 31.3° ± 0.3°, 31.6° ± 0.3°, 31.8° ± 0.3°, 32.2° ± 0.3°, 32.6° ± 0.3°, 33.1° ± 0.3°, 33.4° ± 0.3°, 33.8° ± 0.3°, 34.0° ± 0.3°, 34.2° ± 0.3°, and 34.6° ± 0.3° 2θ. [246] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising peaks at 4.9° ± 0.3°, 8.5° ± 0.3°, 9.5° ± 0.3°, 9.8° ± 0.3°, 11.0° ± 0.3°, 12.1° ± 0.3°, 12.8° ± 0.3°, 13.9° ± 0.3°, 14.4° ± 0.3°, 14.8° ± 0.3°, 15.2° ± 0.3°, 16.2° ± 0.3°, 16.3° ± 0.3°, 16.5° ± 0.3°, 16.9° ± 0.3°, 17.1° ± 0.3°, 17.5° ± 0.3°, 18.0° ± 0.3°, 19.0° ± 0.3°, 19.1° ± 0.3°, 19.8° ± 0.3°, 20.2° ± 0.3°, 20.4° ± 0.3°, 20.7° ± 0.3°, 21.0° ± 0.3°, 21.4° ± 0.3°, 21.6° ± 0.3°, 22.1° ± 0.3°, 22.5° ± 0.3°, 23.1° ± 0.3°, 23.7° ± 0.3°, 23.9° ± 0.3°, 24.3° ± 0.3°, 24.5° ± 0.3°, 24.9° ± 0.3°, 25.1° ± 0.3°, 25.3° ± 0.3°, 25.8° ± 0.3°, 26.3° ± 0.3°, 26.6° ± 0.3°, 26.7° ± 0.3°, 27.1° ± 0.3°, 27.5° ± 0.3°, 27.7° ± 0.3°, 27.9° ± 0.3°, 28.1° ± 0.3°, 28.4° ± 0.3°, 28.7° ± 0.3°, 28.9° ± 0.3°, 29.1° ± 0.3°, 29.5° ± 0.3°, 29.8° ± 0.3°, 30.2° ± 0.3°, 30.7° ± 0.3°, 31.0° ± 0.3°, 31.3° ± 0.3°, 31.6° ± 0.3°, 31.8° ± 0.3°, 32.2° ± 0.3°, 32.6° ± 0.3°, 33.1° ± 0.3°, 33.4° ± 0.3°, 33.8° ± 0.3°, 34.0° ± 0.3°, 34.2° ± 0.3°, 34.6° ± 0.3°, and 34.9° ± 0.3° 2θ. [247] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 4.9° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 8.5° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 9.5° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 9.8° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.0° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.1° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 12.8° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.9° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of Attorney Docket No. SLU-030WO formula (I) has an XRPD pattern comprising a peak at 14.4° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.6° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.8° ± 0.2° 2θ. In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising a peak at 4.9° ± 0.2°, 8.5° ± 0.2°, 9.5° ± 0.2°, 9.8° ± 0.2°, 11.0° ± 0.2°, 12.1° ± 0.2°, 12.8° ± 0.2°, 13.9° ± 0.2°, 14.4° ± 0.2°, and 14.8° ± 0.2° 2θ. [248] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2° ± 0.2°, 16.3° ± 0.2°, 16.5° ± 0.2°, 17.5° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°, 19.1° ± 0.2°, 20.2° ± 0.2°, 20.4° ± 0.2°, 21.0° ± 0.2°, 21.6° ± 0.2°, 22.5° ± 0.2°, 23.7° ± 0.2°, 24.5° ± 0.2°, and 24.9° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.2° ± 0.2°, 16.9° ± 0.2°, 17.1° ± 0.2°, 19.8° ± 0.2°, 20.7° ± 0.2°, 21.4° ± 0.2°, 22.1° ± 0.2°, 23.1° ± 0.2°, 23.9° ± 0.2°, and 24.3° ± 0.2° 2θ. [249] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1° ± 0.2°, 25.3° ± 0.2°, 25.8° ± 0.2°, 27.1° ± 0.2°, 27.5° ± 0.2°, 27.7° ± 0.2°, 28.4° ± 0.2°, 29.5° ± 0.2°, 29.8° ± 0.2°, 31.0° ± 0.2°, and 34.9° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.3° ± 0.2°, 26.6° ± 0.2°, 26.7° ± 0.2°, 27.9° ± 0.2°, 28.1° ± 0.2°, 28.7° ± 0.2°, 28.9° ± 0.2°, 29.1° ± 0.2°, 30.2° ± 0.2°, 30.7° ± 0.2°, 31.3° ± 0.2°, 31.6° ± 0.2°, 31.8° ± 0.2°, 32.2° ± 0.2°, 32.6° ± 0.2°, 33.1° ± 0.2°, 33.4° ± 0.2°, 33.8° ± 0.2°, 34.0° ± 0.2°, 34.2° ± 0.2°, and 34.6° ± 0.2° 2θ. [250] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising peaks at 4.9° ± 0.2°, 8.5° ± 0.2°, 9.5° ± 0.2°, 9.8° ± 0.2°, 11.0° ± 0.2°, 12.1° ± 0.2°, 12.8° ± 0.2°, 13.9° ± 0.2°, 14.4° ± 0.2°, 14.8° ± 0.2°, 15.2° ± 0.2°, 16.2° ± 0.2°, 16.3° ± 0.2°, 16.5° ± 0.2°, 16.9° ± 0.2°, 17.1° ± 0.2°, 17.5° ± 0.2°, 18.0° ± 0.2°, 19.0° ± 0.2°, 19.1° ± 0.2°, 19.8° ± 0.2°, 20.2° ± 0.2°, 20.4° ± 0.2°, 20.7° ± 0.2°, 21.0° ± 0.2°, 21.4° ± 0.2°, 21.6° ± 0.2°, 22.1° ± 0.2°, 22.5° ± 0.2°, 23.1° ± 0.2°, 23.7° ± 0.2°, 23.9° ± 0.2°, 24.3° ± 0.2°, 24.5° ± 0.2°, 24.9° ± 0.2°, 25.1° ± 0.2°, 25.3° ± 0.2°, 25.8° ± 0.2°, 26.3° ± 0.2°, 26.6° ± 0.2°, 26.7° ± 0.2°, 27.1° ± 0.2°, 27.5° ± 0.2°, 27.7° ± 0.2°, 27.9° ± 0.2°, 28.1° ± 0.2°, 28.4° ± 0.2°, 28.7° ± 0.2°, 28.9° ± 0.2°, 29.1° ± 0.2°, 29.5° ± 0.2°, 29.8° ± 0.2°, 30.2° ± 0.2°, 30.7° ± 0.2°, 31.0° ± 0.2°, 31.3° ± 0.2°, 31.6° ± 0.2°, 31.8° ± 0.2°, 32.2° ± 0.2°, 32.6° ± 0.2°, 33.1° ± 0.2°, 33.4° ± 0.2°, 33.8° ± 0.2°, 34.0° ± 0.2°, 34.2° ± 0.2°, 34.6° ± 0.2°, and 34.9° ± 0.2° 2θ. Attorney Docket No. SLU-030WO [251] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 17. [252] In certain embodiments, Form VII of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.7. [253] In certain embodiments, Form VII of the compound of formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form VII of the compound of formula (I) exists in an orthorhombic crystal system and has a P212121 space group. In certain embodiments, Form VII of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 7. Table 7 – Unit Cell Parameters of Form VII of the Compound of Formula (I) a [Å] 7.4800(2) b [Å] 10.8338(3) ) ) [254] In certain embodiments,
Figure imgf000050_0001
Form VII of the compound of formula (I) further comprises water. In certain embodiments, Form VII of the compound of formula (I) has a molar ratio of methanol to water of about 1:1. (E) Form VIII [255] In one aspect, provided herein is Form VIII of a compound of formula (I). [256] In certain embodiments, Form VIII of the compound of formula (I) is a crystalline ethylene glycol solvate. In certain embodiments, Form VIII of the compound of formula (I) is a crystalline mono-ethylene glycol solvate. [257] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 8.9° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.4° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern Attorney Docket No. SLU-030WO comprising a peak at about 13.1° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.0° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at about 8.9°, about 11.4°, about 13.1°, about 14.0°, and about 14.3° 2θ. [258] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 17.3°, about 18.8°, about 21.2°, about 21.9°, about 22.5°, about 23.7°, and about 24.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.9°, about 17.9°, about 20.3°, about 23.0°, about 23.2°, and about 24.0° 2θ. [259] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.3°, about 25.7°, about 26.1°, about 28.3°, about 29.3°, about 29.5°, and about 30.5° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.9°, about 26.4°, about 27.2°, about 27.9°, about 28.8°, about 29.0°, about 30.0°, about 30.9°, about 31.4°, about 31.6°, about 32.1°, about 32.4°, about 33.4°, about 34.0°, about 34.3°, and about 34.6° 2θ. [260] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at about 8.9°, about 11.4°, about 13.1°, about 14.0°, about 14.3°, about 16.0°, about 16.9°, about 17.3°, about 17.9°, about 18.8°, about 20.3°, about 21.2°, about 21.9°, about 22.5°, about 23.0°, about 23.2°, about 23.7°, about 24.0°, about 24.2°, about 25.3°, about 25.7°, about 25.9°, about 26.1°, about 26.4°, about 27.2°, about 27.9°, about 28.3°, about 28.8°, about 29.0°, about 29.3°, about 29.5°, about 30.0°, about 30.5°, about 30.9°, about 31.4°, about 31.6°, about 32.1°, about 32.4°, about 33.4°, about 34.0°, about 34.3°, and about 34.6° 2θ. [261] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 8.9° ± 0.3° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.4° ± 0.3° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.1° ± 0.3° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.0° ± 0.3° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a Attorney Docket No. SLU-030WO peak at 14.3° ± 0.3° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ± 0.3°, 11.4° ± 0.3°, 13.1° ± 0.3°, 14.0° ± 0.3°, and 14.3° ± 0.3° 2θ. [262] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0° ± 0.3°, 17.3° ± 0.3°, 18.8° ± 0.3°, 21.2° ± 0.3°, 21.9° ± 0.3°, 22.5° ± 0.3°, 23.7° ± 0.3°, and 24.2° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.9° ± 0.3°, 17.9° ± 0.3°, 20.3° ± 0.3°, 23.0° ± 0.3°, 23.2° ± 0.3°, and 24.0° ± 0.3° 2θ. [263] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.3° ± 0.3°, 25.7° ± 0.3°, 26.1° ± 0.3°, 28.3° ± 0.3°, 29.3° ± 0.3°, 29.5° ± 0.3°, and 30.5° ± 0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.9° ± 0.3°, 26.4° ± 0.3°, 27.2° ± 0.3°, 27.9° ± 0.3°, 28.8° ± 0.3°, 29.0° ± 0.3°, 30.0° ± 0.3°, 30.9° ± 0.3°, 31.4° ± 0.3°, 31.6° ± 0.3°, 32.1° ± 0.3°, 32.4° ± 0.3°, 33.4° ± 0.3°, 34.0° ± 0.3°, 34.3° ± 0.3°, and 34.6° ± 0.3° 2θ. [264] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ± 0.3°, 11.4° ± 0.3°, 13.1° ± 0.3°, 14.0° ± 0.3°, 14.3° ± 0.3°, 16.0° ± 0.3°, 16.9° ± 0.3°, 17.3° ± 0.3°, 17.9° ± 0.3°, 18.8° ± 0.3°, 20.3° ± 0.3°, 21.2° ± 0.3°, 21.9° ± 0.3°, 22.5° ± 0.3°, 23.0° ± 0.3°, 23.2° ± 0.3°, 23.7° ± 0.3°, 24.0° ± 0.3°, 24.2° ± 0.3°, 25.3° ± 0.3°, 25.7° ± 0.3°, 25.9° ± 0.3°, 26.1° ± 0.3°, 26.4° ± 0.3°, 27.2° ± 0.3°, 27.9° ± 0.3°, 28.3° ± 0.3°, 28.8° ± 0.3°, 29.0° ± 0.3°, 29.3° ± 0.3°, 29.5° ± 0.3°, 30.0° ± 0.3°, 30.5° ± 0.3°, 30.9° ± 0.3°, 31.4° ± 0.3°, 31.6° ± 0.3°, 32.1° ± 0.3°, 32.4° ± 0.3°, 33.4° ± 0.3°, 34.0° ± 0.3°, 34.3° ± 0.3°, and 34.6° ± 0.3° 2θ. [265] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 8.9° ± 0.2° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 11.4° ± 0.2° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 13.1° ± 0.2° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.0° ± 0.2° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising a peak at 14.3° ± 0.2° 2θ. In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ± 0.2°, 11.4° ± 0.2°, 13.1° ± 0.2°, 14.0° ± 0.2°, and 14.3° ± 0.2° 2θ. Attorney Docket No. SLU-030WO [266] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0° ± 0.2°, 17.3° ± 0.2°, 18.8° ± 0.2°, 21.2° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 23.7° ± 0.2°, and 24.2° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.9° ± 0.2°, 17.9° ± 0.2°, 20.3° ± 0.2°, 23.0° ± 0.2°, 23.2° ± 0.2°, and 24.0° ± 0.2° 2θ. [267] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.3° ± 0.2°, 25.7° ± 0.2°, 26.1° ± 0.2°, 28.3° ± 0.2°, 29.3° ± 0.2°, 29.5° ± 0.2°, and 30.5° ± 0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.9° ± 0.2°, 26.4° ± 0.2°, 27.2° ± 0.2°, 27.9° ± 0.2°, 28.8° ± 0.2°, 29.0° ± 0.2°, 30.0° ± 0.2°, 30.9° ± 0.2°, 31.4° ± 0.2°, 31.6° ± 0.2°, 32.1° ± 0.2°, 32.4° ± 0.2°, 33.4° ± 0.2°, 34.0° ± 0.2°, 34.3° ± 0.2°, and 34.6° ± 0.2° 2θ. [268] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising peaks at 8.9° ± 0.2°, 11.4° ± 0.2°, 13.1° ± 0.2°, 14.0° ± 0.2°, 14.3° ± 0.2°, 16.0° ± 0.2°, 16.9° ± 0.2°, 17.3° ± 0.2°, 17.9° ± 0.2°, 18.8° ± 0.2°, 20.3° ± 0.2°, 21.2° ± 0.2°, 21.9° ± 0.2°, 22.5° ± 0.2°, 23.0° ± 0.2°, 23.2° ± 0.2°, 23.7° ± 0.2°, 24.0° ± 0.2°, 24.2° ± 0.2°, 25.3° ± 0.2°, 25.7° ± 0.2°, 25.9° ± 0.2°, 26.1° ± 0.2°, 26.4° ± 0.2°, 27.2° ± 0.2°, 27.9° ± 0.2°, 28.3° ± 0.2°, 28.8° ± 0.2°, 29.0° ± 0.2°, 29.3° ± 0.2°, 29.5° ± 0.2°, 30.0° ± 0.2°, 30.5° ± 0.2°, 30.9° ± 0.2°, 31.4° ± 0.2°, 31.6° ± 0.2°, 32.1° ± 0.2°, 32.4° ± 0.2°, 33.4° ± 0.2°, 34.0° ± 0.2°, 34.3° ± 0.2°, and 34.6° ± 0.2° 2θ. [269] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 18. [270] In certain embodiments, Form VIII of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.8. [271] In certain embodiments, Form VIII of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form VIII of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. In certain embodiments, Form VIII of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 8. Attorney Docket No. SLU-030WO Table 8 – Unit Cell Parameters of Form VIII of the Compound of Formula (I) a [Å] 9.9733(4) b [Å] 7.9063(3) ) (F) Form IX
Figure imgf000054_0001
[272] In one aspect, provided herein is Form IX of a compound of formula (I). [273] In certain embodiments, Form IX of the compound of formula (I) is a crystalline acetone solvate. In certain embodiments, Form IX of the compound of formula (I) is a crystalline mono-acetone solvate. [274] In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 7.1° 2θ. In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 9.5° 2θ. In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.5° 2θ. In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.1° 2θ. In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ. In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising peaks at about 7.1°, about 9.5°, about 10.5°, about 13.1°, and about 14.3° 2θ. [275] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.6°, about 16.2°, about 18.0°, about 18.9°, about 21.1°, and about 24.8° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 18.8°, about 19.6°, about 21.4°, about 21.9°, about 22.5°, about 22.8°, and about 24.5° 2θ. [276] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.3°, about 25.8°, about 26.4°, about 27.0°, about 28.2°, about 31.4°, about 31.8°, and about 33.0° 2θ. In certain embodiments, the XRPD pattern further Attorney Docket No. SLU-030WO comprises one or more peaks selected from about 25.2°, about 26.6°, about 28.7°, about 29.1°, about 29.2°, about 30.7°, about 33.3°, about 34.3°, and about 34.8° 2θ. [277] In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising peaks at about 7.1°, about 9.5°, about 10.5°, about 13.1°, about 14.3°, about 15.6°, about 16.2°, about 18.0°, about 18.8°, about 18.9°, about 19.6°, about 21.1°, about 21.4°, about 21.9°, about 22.5°, about 22.8°, about 24.5°, about 24.8°, about 25.2°, about 25.3°, about 25.8°, about 26.4°, about 26.6°, about 27.0°, about 28.2°, about 28.7°, about 29.1°, about 29.2°, about 30.7°, about 31.4°, about 31.8°, about 33.0°, about 33.3°, about 34.3°, and about 34.8° 2θ. [278] In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 19. [279] In certain embodiments, Form IX of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.9. [280] In certain embodiments, Form IX of the compound of formula (I) exists in a monoclinic crystal system. In certain embodiments, Form IX of the compound of formula (I) exists in a monoclinic crystal system and has a P1211 space group. In certain embodiments, Form IX of the compound of formula (I) is characterized by the crystallographic unit cell parameters as set forth in Table 9. Table 9 – Unit Cell Parameters of Form IX of the Compound of Formula (I) a [Å] 9.5578(11) Å )
Figure imgf000055_0001
(4) Chemical Purity of Crystalline Forms of a Compound of Formula (I) [281] In certain embodiments, a crystalline form of a compound of formula (I) described herein has a chemical purity of about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to Attorney Docket No. SLU-030WO about 100%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%. [282] In certain embodiments, a crystalline form of a compound of formula (I) described herein has a chemical purity of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9%. [283] In certain embodiments, a crystalline form of a compound of formula (I) described herein has a chemical purity of about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, about 99.9%, or about 100%. Pharmaceutical Compositions [284] In one aspect, provided herein are pharmaceutical compositions generally comprising a compound of formula (I) (e.g., a crystalline form of the compound of formula (I) described herein, such as, for example, Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X of the compound of formula (I)), and a pharmaceutically acceptable excipient, for the treatment of a condition, disease or disorder described herein. [285] In various embodiments, provided herein is a pharmaceutical composition comprising a crystalline form of the compound of formula (I) described herein (e.g., Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X), and a pharmaceutically acceptable excipient thereof. [286] In various embodiments, provided herein is a pharmaceutical composition comprising two or more crystalline forms of the compound of formula (I) described herein, and a pharmaceutically acceptable excipient thereof. Attorney Docket No. SLU-030WO [287] In certain embodiments, the pharmaceutical compositions described herein may be administered in a unit dosage form and may be prepared by any method well known in the art of pharmacy. The amounts of the compound of formula (I) (e.g., a crystalline form of the compound of formula (I) described herein, such as, for example, Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X of the compound of formula (I)) present in a single dosage form may vary depending upon the patient being treated and/or the particular mode of administration. [288] The pharmaceutical compositions provided herein can be administered by a variety of routes including, but not limited to, oral (enteral) administration, parenteral (by injection) administration, rectal administration, transdermal administration, intradermal administration, intrathecal administration, subcutaneous (SC) administration, intravenous (IV) administration, intramuscular (IM) administration, and intranasal administration. [289] The pharmaceutical compositions provided herein may also be administered chronically (“chronic administration”). Chronic administration refers to administration of a compound or pharmaceutical composition thereof over an extended period of time, e.g., for example, over 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or may be continued indefinitely, for example, for the rest of the subject’s life. In certain embodiments, the chronic administration is intended to provide a constant level of the compound (e.g., a compound of formula (I)) in the blood, e.g., within the therapeutic window over the extended period of time. [290] The pharmaceutical compositions provided herein may be presented in unit dosage forms to facilitate accurate dosing. The term “unit dosage forms” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. Typical unit dosage forms include prefilled, premeasured ampules or syringes of a liquid pharmaceutical composition or pills, tablets, capsules or the like in the case of solid pharmaceutical compositions. [291] Pharmaceutical compositions that are suitable for oral administration can be provided as discrete dosage forms, such as, but not limited to, tablets (e.g., chewable tablets), caplets, capsules, and liquids (e.g., flavored syrups). Such dosage forms contain predetermined amounts of active ingredients, and may be prepared by methods of pharmacy well known to Attorney Docket No. SLU-030WO those skilled in the art. See generally, Remington’s Pharmaceutical Sciences, 18th ed., Mack Publishing, Easton PA (1990). [292] Oral dosage forms provided herein are prepared by combining the active ingredients in an intimate admixture with at least one excipient according to conventional pharmaceutical compounding techniques. Excipients can take a wide variety of forms depending on the form of preparation desired for administration. For example, excipients suitable for use in oral liquid or aerosol dosage forms include, but are not limited to, water, glycols, oils, alcohols, flavoring agents, preservatives, and coloring agents. Examples of excipients suitable for use in solid oral dosage forms (e.g., powders, tablets, capsules, and caplets) include, but are not limited to, fillers, diluents, granulating agents, lubricants, binders, and disintegrating agents. [293] In various embodiments, the pharmaceutical compositions described herein may be in the form of an oral dosage form, such as a tablet or a capsule, in which case solid excipients are employed. In certain embodiments, the tablets can be coated by standard aqueous or nonaqueous techniques. Such dosage forms can be prepared by any of the methods of pharmacy. In general, pharmaceutical compositions and dosage forms are prepared by uniformly and intimately admixing the active ingredients with liquid carriers, finely divided solid carriers, or both, and then shaping the product into the desired presentation if necessary. [294] In certain embodiments, the compound of formula (I) (e.g., a crystalline form of the compound of formula (I) described herein, such as, for example, Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X of the compound of formula (I)) can be administered as the sole active agent, or they can be administered in combination with other active agents. [295] Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with ordinary experimentation. General considerations in the formulation and/or manufacture of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005. Attorney Docket No. SLU-030WO Second Active Agents [296] A compound provided herein (e.g., a compound of formula (I)) can be combined with other pharmacologically active compounds ("second active agents") in methods and compositions provided herein. Certain combinations may work synergistically in the treatment of particular types of diseases or disorders, and conditions and symptoms associated with such diseases or disorders. A compound provided herein (e.g., a compound of formula (I)) can also work to alleviate adverse effects associated with certain second active agents, and vice versa. [297] One or more second active ingredients or agents can be used in the methods and compositions provided herein. Second active agents can be large molecules (e.g., proteins) or small molecules (e.g., synthetic inorganic, organometallic, or organic molecules). [298] Administration of a compound provided herein (e.g., a compound of formula (I)) and the second active agents to a patient can occur simultaneously or sequentially by the same or different routes of administration. The suitability of a particular route of administration employed for a particular active agent will depend on the active agent itself (e.g., whether it can be administered orally without decomposing prior to entering the blood stream) and the disease being treated. One route of administration for compounds provided herein is oral. Routes of administration for the second active agents or ingredients are known to those of ordinary skill in the art. See, e.g., Physicians' Desk Reference (60.sup.th ed., 2006). [299] In another aspect, the second active agent is administered intravenously or subcutaneously and once or twice daily in an amount of from about 1 to about 1000 mg, from about 5 to about 500 mg, from about 10 to about 350 mg, or from about 50 to about 200 mg. The specific amount of the second active agent will depend on the specific agent used, the type of disease being treated or managed, the severity and stage of disease, and the amount(s) of compounds provided herein and any optional additional active agents concurrently administered to the patient. [300] As discussed elsewhere herein, also encompassed is a method of reducing, treating and/or preventing adverse or undesired effects associated with conventional therapy including, but are not limited to, surgery, chemotherapy, radiation therapy, hormonal therapy, biological therapy, and immunotherapy. Compounds provided herein (e.g., a compound of Attorney Docket No. SLU-030WO formula (I) and other active ingredients can be administered to a patient prior to, during, or after the occurrence of the adverse effect associated with conventional therapy. EXAMPLES [301] In order that the disclosure described herein may be more fully understood, the following examples are set forth. The synthetic and biological examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope. General Analytical Methods Single Crystal Structure Determination [302] Single-crystal X-ray data were obtained for Forms I – IX of the compound of formula (I) on a Bruker D8 single-crystal X-ray diffractometer system (λ = 1.54180 Å). The frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. The structure of each crystal form was solved and refined using the Bruker SHELXTL Software Package. Characterization by X-ray Powder Diffraction (XRPD) [303] XRPD data were recorded at room temperature using one of the three methods below: [304] Method 1: XRPD patterns were obtained on an Aeris X-ray diffractometer (Malvern PANalytical B.V., Almelo, The Netherlands) using the Cu Kα radiation (λ = 1.54 Ǻ) at 40 kV, 15 mA passing through a Ni monochromator. Data were collected in a continuous scan mode with a step size of 0.02° and a dwell time of 149 s over a 3° to 40° 2θ angular range. Samples were loaded on a zero-background holder and gently pressed with a clean glass slide to ensure coplanarity of the sample surface with the surface of the holder. Diffractograms were analyzed and plotted with the HighScore Plus software (V 5.0; Malvern PANalytical B.V., Almelo, The Netherlands). [305] Method 2: XRPD data were collected using a Bruker D2 Phaser Benchtop X-ray Powder diffractometer (Bruker, Billerica, MA, USA) using the Cu Kα1 radiation (λ = 1.54184 Å) equipped with a solid state LynxEye (1D mode) detector. Samples were prepared on a Si low-background holder. Samples were used as is or were ground in a mortar and pestle. Attorney Docket No. SLU-030WO [306] Method 3: Alternatively, XRPD patterns were generated from single-crystal X-ray diffraction data using Cambridge Crystallographic Data Centre (CCDC) Mercury 2022.2.0 (Build 353591) as described in C. F. Macrae, et al, J. Appl. Cryst., 53, 2020, 226-235. Differential Scanning Calorimetry (DSC) [307] DSC experiments were performed using one of the two setups below: [308] Method 1: The sample cell of a Discovery DSC 2500 instrument (TA® Instruments, New Castle, Delaware, USA), equipped with a refrigerated cooling system (RCS90), was purged with dry nitrogen at a flow rate of 50 mL/min. Accurately weighed samples (2−5 mg), placed in Tzero hermetic pans, were then scanned at a heating rate of 10°C/min over the desired temperature range, typically 25 to 300°C. [309] Method 2: Samples were placed in a 40µL aluminum pan in a DSC3 instrument (Mettler Toledo, Columbus, OH, USA). The temperature was ramped from 25 to 300°C at 5°C/min. The STARe software (Mettler Toledo, Columbus, OH, USA) was used to process the data. Thermogravimetric Analysis (TGA) [310] Samples were weighed and placed in aluminum pans in the sample cell of a Discovery TGA 5500 instrument (TA® Instruments, New Castle, Delaware, USA), operating with the TRIOS software (Version 5.0), or a Shimadzu DTG-60 instrument (Shimadzu Scientific Instruments, Inc., Columbia. MD, USA). The sample cell was then purged with dry nitrogen at a flow rate of 15 mL/min. A heating rate of 10°C/min from 25−350 °C was used and data were recorded. Dynamic Vapor Sorption (DVS) [311] Moisture sorption/desorption data were collected on a DVS-intrinsic vapor sorption analyzer (Surface Measurement Systems NA, Allentown, PA, USA), operating with the DVS-intrinsic control software (Version 1.0.5.1). Samples were not dried prior to analysis. Sorption and desorption data were collected over a range from 5% to 98% relative humidity (RH) via 10% RH increments under a nitrogen purge. The equilibrium criterion used for analysis was less than 0.005% weight change in 10 min with a maximum equilibration time of 3 h. Attorney Docket No. SLU-030WO Karl-Fisher Water Content (KF) [312] KF measurement was performed with a Metrohm 756 Coulometer (Metrohm, Riverview, FL, USA). Compound (about 60 mg, accurately weighed) was dissolved in 3 mL of anhydrous tetrahydrofuran in a vial. The vial was capped and shaken by hand until the compound dissolved and a clear solution was obtained. An aliquot of this solution (approximately 0.6 mL, accurately measured) was then injected into the KF instrument. The measure was done in triplicate and the average water content (in parts per million, ppm) was determined and used to calculate the percentage of water in the solid material. Example 1: Synthesis of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione [313] Reaction temperatures are reported as internal temperatures. Chemical intermediates, reagents, and solvents were obtained from commercial sources. Preparation of 2-methyl-6-nitro-4H-3,1-benzoxazin-4-one [314] 2-Amino-5-
Figure imgf000062_0001
was mixed with acetic anhydride (800 mL, 8.47 mol, 3.86 eq.) and then heated to 120°C in an oil bath for 2 hours. The resulting mixture was cooled to 25 ± 5°C overnight. After cooling to between 0 and 5°C, the mixture was held at the same temperature for 3 h. The solid was collected by filtration and rinsed with methyl-t-butylether (MTBE, 200 mL × 3) to give a wet cake (417.5 g). The wet cake was dried at 50 ± 5°C under reduced pressure for 18 h to give 2-methyl-6-nitro-4H- 3,1-benzoxazin-4-one (384.1 g). Quantitative nuclear magnetic resonance spectrometry (QNMR) indicated that the potency of the product was 99.4% w/w.1H NMR (Deuterated dimethyl sulfoxide (DMSO-d6) δ (ppm): 2.40 (s, 3H), 7.75-7.80 (dd, 1H), 7.86-7.93 (dd, 1H), 8.00-8.08 (t, 1H) Attorney Docket No. SLU-030WO Preparation of 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione charged
Figure imgf000063_0001
(445.4 g, 2.71 mol, 1.3 eq.) was then added followed by 2 L of isopropyl acetate. The resulting mixture was stirred at 25 ± 5°C. Propylphosphonic anhydride (T3P) in ethyl acetate (2.478 L, 4.16 mol, 2.0 eq.) was charged into the reactor via a pump, which was then rinsed with isopropyl acetate (500 mL). The resulting mixture was heated to 88 ± 5°C. After 32 h, additional T3P in ethyl acetate (197 mL, 0.15 eq.) was charged into the reactor and heating at 88 ± 5°C was maintained for another 24h. After a total reaction time of 56h, the mixture was cooled to 25 ± 5°C and the solid material was collected by filtration. The wet cake was rinsed with isopropyl acetate (960 mL × 3) and dried under reduced pressure with a nitrogen sweep at 25 ± 5 °C to constant weight (about 24h) to give 789.2 g 3-(2-methyl-5-nitro-4-oxo-3H- quinazolin-3-yl)-2,6-piperidinedione with 72.5 % w/w potency (by QNMR), which was used as is for the next synthetic step. Preparation of 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione
Figure imgf000063_0002
% w/w potency, 1.559 mol) was changed in a 20L jacketed reactor. Anhydrous acetonitrile (4356 g, 10 v/w) was added via cannula transfer under nitrogen followed by triethylamine (3842 g, 37.4 mol, 24 eq.) and then chlorotrimethylsilane (1420 g, 12.47 mol, 8 eq.), again using a cannula. The resulting slurry was heated to 57 ± 3°C and kept at the same temperature for 18 h. A small sample was pulled, quenched with deuterium oxide (D2O), and analyzed by 1H NMR, which indicated almost complete disappearance of the starting material (2 % based
Figure imgf000063_0003
the relative area of the resonance corresponding to the proton at the chiral center remained). Attorney Docket No. SLU-030WO [317] The total reaction mixture was then cooled to 25 ± 5 °C. A solid (hydrochloride salt of triethylamine) was removed by filtration and rinsed with anhydrous acetonitrile (3 L). The 20 L jacketed reactor was cleaned with deionized water and
Figure imgf000064_0001
then dried with a strong nitrogen flow for 20 min. D2O (950 g, 30 eq.) was charged into the dried 20 L jacketed reactor and cooled to 5-10°C. The filtrate was then added to the D2O portion wise using a pump such that the inner temperature of the reactor was maintained below 45 °C (the maximum temperature observed was 35°C). The resulting slurry was stirred at 25 ± 5°C for 4 h and then cooled to -4°C and stirred for 2 days (over the weekend). After warming up to 25 ± 5°C, the mixture was concentrated under reduced pressure to about 3.5 L while the temperature was kept below 35 °C. Deionized water (3.5 L, 6.4 vol.) was then charged into the mixture to precipitate 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione. The solid was filtered and the wet cake was rinsed with deionized water (1 L × 5). A sample was removed and analyzed by 1H NMR (about 94 % deuterium at the chiral center). The wet cake was dried under reduced pressure with a nitrogen sweep at 25 ± 5 °C for 18 h to give the product (425 g, potency: 99.6 % w/w by QNMR, purity: 97.6% by high-performance liquid chromatography (HPLC)).1H NMR (DMSO-d6) δ (ppm): 2.12 - 2.20 (m, 1 H), 2.51 - 2.62 (m, 2H), 2.66 (s, 3H), 2.72 - 2.88 (m, 1H), 5.30 (m, 0.06 H), 7.78 - 7.86 (2 dd, 2 H), 7.93 - 7.99 (t, 1 H), 11.07 (s, 1 H) Preparation of 3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione
Figure imgf000064_0002
(193.8 g, 0.611 mol, 1.0 eq.) was charged into a Parr reactor. N,N-dimethylacetamide (DMAc, 1.5 L, 7.5 v/w) and wet 10% palladium on carbon (Pd/C; 19.3 g, 18 mmol, 0.03 eq.) were added. The reaction mixture was heated at 50°C under 50 psi hydrogen for 1.5 h until the hydrogen gas mass flow dropped below 1 sccm. The mixture was cooled to room temperature and the unfiltered mixture was transferred into a container. [319] A second batch of racemic 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione (196.7 g, 0.611 mol, 1.0 eq.) was treated similarly and the resulting unfiltered mixture was combined with the material from the first batch. Attorney Docket No. SLU-030WO [320] After filtration through a Celite pad, the filtrate was charged into a 20 L reactor. Deionized water (600 mL) was added, and the resulting mixture was heated to 40 °C. Seed crystals of 3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (3. 0g) were added into the reactor and deionized water (3.2L total) was added. The mixture was cooled to 20°C. The solid that formed was collected by filtration. It was rinsed with a DMAc:H2O mixture (1:1 v/v; 1000 mL) and then with deionized water (3 x 800 mL). The wet cake was dried under reduced pressure with a nitrogen sweep at 25 ± 5°C for 18 h to give the product (272 g, 75%). QNMR analysis indicated a potency of the solid of 98 % w/w resulting in a 75 % yield.1H NMR (DMSO-d6) δ (ppm): 2.10 - 2.23 (m, 1 H), 2.47-2.53 (m, 5 H), 2.76 - 2.86 (m, 1 H), 5.25-5.38 (dd, 0.05 H), 6.53 – 6.59 (ddd, 2 H), 7.01 (br s, 2H), 7.32 – 7.37 (t, 1 H), 10.97 (br s, 1 H) Preparation of (S)-3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione  
Figure imgf000065_0001
(287.1g, 1.0 mol) and D-dibutyltin diacetate (D-DBTA; 895.8 g) were charged into a 20 L jacketed reactor. Acetonitrile (18.8L, 65 vol.) was added and the mixture was stirred at 25°C for 15 min. Seed crystals of the D-DBTA salt of (S)-3-(2-methyl-5-amino-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (2.36 g) were then added to the mixture, which was heated to 55 °C over 45 min and kept at 55°C for an additional 30 min. The reaction mixture was then cooled to 20°C stepwise over about 6 h (20 steps of 20 min each), following a quadratic cooling curve, and stirred at 20°C overnight. A sample of the solid that formed was pulled to determine chiral purity by chiral HPLC and the chiral ratio of the solid Attorney Docket No. SLU-030WO was shown to be approximately 96:4 (S:R). The solid was collected by filtration and rinsed with a 25 mg/mL D-DBTA solution in acetonitrile (3.5 L, 12 vol.), added in 3 portions. The chiral purity of the wet cake was 98.6% (chiral HPLC). [322] The wet cake was charged into a container and a small amount of 2- methyltetrahydrofuran (MeTHF, from a total of 5.8 L, 20 vol.) was added to form a slurry, which was charged into a 20L jacketed reactor. The remaining MeTHF was then added to the reactor, followed by 1.86 L (6.5 vol.) of an 8% sodium bicarbonate solution in water. The mixture was stirred for 5 min then left to settle for 5 min. The aqueous layer was separated and then extracted twice with additional MeTHF (1.8 L, 6.5 vol.). The organic layer was combined with the MeTHF extractions and washed with a 4% sodium bicarbonate solution (435 mL,1.5 vol) and deionized water (580 mL, 2 vol.), twice sequentially. The organic phase was then concentrated by vacuum distillation to ~900mL (3 vol.) while keeping the temperature below 35°C (the max. observed temperature was 25°C). MeTHF (600 mL, 2 vol) was added to the mixture, and the solvent was removed by distillation. The solid that formed (160.6 g) was collected by filtration. The filtrate (~375 mL) was extracted with MeTHF (375 mL, twice) and then concentrated under reduced pressure to give additional solid material (1.6 g). The two solids were mixed, and MeTHF (300 mL) was added. The resulting slurry was charged into a 20 L jacketed reactor and isopropanol (IPA, 4.350 L, 15 vol.) was added into the reactor over 30 min using a pump. The slurry was kept at 4 °C overnight. The batch was then concentrated to ~2.5 L (8.5 vol.) by evaporation under reduced pressure while keeping the temperature below 35 °C. The resulting mixture was stirred at 20 °C for 1 h. The solid was collected by filtration and rinsed with IPA (twice 290mL, 1 vol.). The wet cake was dried under reduced pressure with a nitrogen sweep at 25 ± 5 °C for 18 h to give the title compound as a crystalline off-white solid (105 g).1H NMR (pyridine-d5) δ (ppm): 2.20 (m, 1 H), 2.67 (s, 3 H), 2.91 (m, 2 H), 3.08 (m, 1 H), 5.35 (dd, 0.06 H), 6.79 (d, 1H) 7.02 (d, 1 H) 7.43 (t, 1 H), 7.66 (br s, 2 H), 13.12 (s, 1 H). Purity: 99.8% (HPLC). Chiral purity: 98.4% (chiral HPLC). Deuterium content at C3: 94.0% (1H NMR). Water content: 1.2% (Karl-Fisher). The obtained crystalline material was shown by XRPD to be a mixture of anhydrous form I and monohydrate form II as shown in Example 3 below. Attorney Docket No. SLU-030WO Example 2: Preparation and Characterization of Crystalline Forms I to X of the Free Base of (S)-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione [323] Form I was obtained by stirring and sonicating a glassy form of the free base of (S)-3- (5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (obtained by separation of the racemic mixture using chiral supercritical fluid chromatography as described in Jacques et al, Proc Natl Acad Sci U.S.A.2015, 112, E1471-E1479) in isopropanol until a white slurry was obtained. The white solid (anhydrous Form I) was then filtered and dried under vacuum. [324] Form II was prepared as follows. SP-3164 (596 g MeTHF solution containing 8.7 g the free base of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione, prepared as described in Example 1 and obtained during the isolation of the free base by extraction) was concentrated to 50 g under reduced pressure. MeTHF (140 mL) was added, and the mixture was further concentrated to about 25 g. Isopropanol (50 mL) was then added and the heterogenous mixture was sonicated for about 2 min to form a white slurry. Solvents were evaporated under reduced pressure to a weight of about 25 g. Fresh isopropanol (50 mL) was added, and the mixture was left to age for about 5 min. The solid was filtered through a fritted funnel and rinsed with 15 mL IPA. The filter cake was dried under nitrogen for 1 h until constant mass. The off-white solid collected was ground into a fine powder using a mortar and pestle (6.5 g) at room temperature in relative humidity (RH) > 50%. It was shown to be monohydrate Form II by single crystal X Ray diffraction analysis. [325] Form III was obtained by dissolving the free base of (S)-3-(5-amino-2-methyl-4-oxo- 3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (200 mg, prepared as described in Example 1) in MeTHF (4 mL) in a 25 mL jacketed reactor. As the temperature was ramped up to 60 °C, isopropanol (2 mL) was added. The mixture was aged at that temperature for 16 h (overnight). It was then cooled to 20 °C and heptane (5 mL) was added. A crystalline material (Form III) formed, was filtered, and then dried under vacuum with nitrogen (100 mg, white powder). [326] For the preparation of single crystals of solid crystalline Forms I to IX, about 30 mg of the free base of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione (Form I, prepared as described above in this example) was dissolved in the minimum amount of each of the solvents listed below (Table 10) while heating at 80 °C. The Attorney Docket No. SLU-030WO resulting solutions were cooled to ambient temperature and the solvent was allowed to slowly evaporate until formation of a crystalline solid. Table 10 – Solvents Used for Crystallization of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione and Resulting Crystal Forms I to IX Solvent Crystal Form Attribute Isopropanol Form I Anhydrous
Figure imgf000068_0001
[327] Slurrying the anhydrous crystalline form I of the free base of (S)-3-(5-amino-2- methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (prepared as described above) in ethyl acetate at 40°C for about 3h resulted in the formation of anhydrous crystalline Form X. [328] For each Form I-IX, a single crystal was analyzed by X-ray diffraction to determine the crystal structure and unit cell. Calculated XRPD data (generated from the single crystal X-ray data for Form I through Form IX and obtained from powder for Forms I and X) are shown in FIGs 1-10 and 2θ angles are presented in Tables 11-20 (Forms I to X). X-ray crystal structures (ORTEP drawings) are shown in FIGs 11-19 and unit cell parameters are presented in Tables 21-29.
Attorney Docket No. SLU-030WO Table 11 – Calculated XRPD Data for Form I of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 10.3 807.6 8.1
Figure imgf000069_0001
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 35.8 457.7 4.6 Table 12 – Calculated X
Figure imgf000070_0001
o-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 6.9 1292.7 12.9
Figure imgf000070_0002
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 31.4 315.3 3.1 Table 13 – Calculated XR
Figure imgf000071_0001
no-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 10.7 9998.8 100.0
Figure imgf000071_0002
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 24.7 3075.9 30.8
Figure imgf000072_0001
Attorney Docket No. SLU-030WO Table 14 – Calculated XRPD Data for Form IV of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 7.2 6405.9 63.5
Figure imgf000073_0001
Attorney Docket No. SLU-030WO Table 15 – Calculated XRPD Data for Form V of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 7.6 606.1 6.1
Figure imgf000074_0001
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 32.8 164.1 1.6 Table 16 – Calculated XR
Figure imgf000075_0001
ata or orm o ()--(- mno-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 8.5 1070.0 10.5
Figure imgf000075_0002
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 25.5 2585.7 25.4
Figure imgf000076_0001
Attorney Docket No. SLU-030WO Table 17 – Calculated XRPD Data for Form VII of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 4.9 14.3 0.1
Figure imgf000077_0001
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 26.6 936.5 9.4
Figure imgf000078_0001
Attorney Docket No. SLU-030WO Table 18 – Calculated XRPD Data for Form VIII of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 8.9 2371.3 23.7
Figure imgf000079_0001
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 34.3 363.9 3.6 Table 19 – Calculated XR
Figure imgf000080_0001
no-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione Pos. [°2θ] Height [cts] Rel. Int. [%] 7.1 4595.8 45.1
Figure imgf000080_0002
Attorney Docket No. SLU-030WO Pos. [°2θ] Height [cts] Rel. Int. [%] 27.0 1636.4 16.1 Table 20 – XRPD Data f
Figure imgf000081_0001
-4-oxo-3H-quinazolin-3-yl)- [3-2H]-2,6-piperidinedione Pos. Height [°2θ] [cts] Rel. Int. [%]
Figure imgf000081_0002
Attorney Docket No. SLU-030WO Pos. Height [°2θ] [cts] Rel. Int. [%] Table 21 – Cell Unit Para
Figure imgf000082_0001
meters of Form I Chemical formula C7H7N2O1.50 Formula weight 143.15 g/mol
Figure imgf000082_0002
Attorney Docket No. SLU-030WO Table 22 – Cell Unit Parameters of Form II Chemical formula C14H14N4O4 Formula weight 302.29 g/mol Temperature 298(2) K
Figure imgf000083_0001
Chemical formula C14H14N4O3 Formula weight 286.29 g/mol
Figure imgf000083_0002
Attorney Docket No. SLU-030WO Table 24 – Cell Unit Parameters of Form IV Chemical formula C16H13N5O3 Formula weight 323.31 g/mol Temperature 298(2) K
Figure imgf000084_0001
Chemical formula C9H11N2O3.50 Formula weight 203.20 g/mol
Figure imgf000084_0002
Attorney Docket No. SLU-030WO Table 26 – Cell Unit Parameters of Form VI Chemical formula C16H20N4O4 Formula weight 332.36 g/mol
Figure imgf000085_0001
Chemical formula C15.50H16N3O4 Formula weight 308.31 g/mol
Figure imgf000085_0002
Attorney Docket No. SLU-030WO Table 28 – Cell Unit Parameters of Form VIII Chemical formula C16H19N4O5 Formula weight 347.35 g/mol Temperature 273(2) K °
Figure imgf000086_0001
Chemical formula C17H20N4O4 Formula weight 344.37 g/mol
Figure imgf000086_0002
[329] Additional DSC, TGA, and dynamic vapor sorption (DVS) data were obtained for Forms I and X, and the data is presented in FIGs 20-23. The TGA data of Form I shows no weight loss between room temperature and 150 °C (FIG.20). Two endothermic peaks, at 243.19 °C (onset 238.03 °C) and 273.90 °C (onset 271.55 °C), are seen in the DSC data (FIG. 20). DVS data of Form I (FIG.21) show water sorption at about 45% relative humidity followed by a plateau. Some hysteresis is observed as the desorption and sorption curves do not match indicating that the solid retains water. XRPD of the solid after DVS shows that the resulting material is likely a mixture of Forms I and II (anhydrous and monohydrate). TGA Attorney Docket No. SLU-030WO of the solid after DVS shows a weight loss of 1.69% below 100 °C. The TGA data of Form X shows no weight loss between room temperature and 150 °C (FIG.22). Two endothermic peaks, at 242.35 °C (onset 235.84 °C) and 282.71 °C (onset 281.87 °C), are seen in the DSC data (FIG.22). DVS data analysis does not show significant hygroscopicity and very limited hysteresis is observed (FIG.23). XRPD data of the material recovered from the DVS experiment after one cycle was substantially similar to the data obtained before the experiment, indicating that the material is stable and remains as Form X. Example 3: Characterization of the Crystalline Free Base of (S)-3-(5-amino-2-methyl-4- oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione from Example 1 Characterization by X-ray Powder Diffraction [330] The XRPD trace of the crystalline product of Example 1 is shown in FIG.24 and characterized by peaks at 2θ angles of 7.25, 10.35, 11.08, 12.02, 13.56, 13.77, 14.13, 14.54, 15.47, 15.8, 17.47, 19.83, 20.72, 21.25, 21.90, 23.33, 24.22, 25.77, 26.79, 28.33, 29.23, 30.45, 33.10. It is a mixture of crystalline forms I and II (see Example 3). Characterization by Differential Scanning Calorimetry [331] A differential scanning calorimetry (DSC) curve of the crystalline material of Example 1 is provided in FIG.25. The DSC curve displayed an endothermic event, with onset and peak values at about 241 ^C and about 243 ^C, respectively, followed by an exothermic event, with onset and peak values at about 245 and 246 ^C, respectively, and a second endothermic event, with onset and peak values at about 253 and 258 ^C, respectively. Characterization by Thermogravimetric Analysis [332] Thermogravimetric analysis (TGA) for the crystalline material of Example 1 is shown in FIG.26. [333] The TGA data showed a mass loss of 1.2 % between 60 °C and 140 °C, and that thermal decomposition occurred above 210 °C. Attorney Docket No. SLU-030WO Example 4: Solubility of the Crystalline Free Base of (S)-3-(5-Amino-2-methyl-4-oxo- 3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione [334] Compound ((S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione (anhydrous crystal form I), (RS)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin- 3-yl)-[3-2H]-2,6-piperidinedione, or (RS)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)- 2,6-piperidinedione) was suspended in a selected solvent (water, methanol, ethanol, 2- propanol, tetrahydrofuran, acetonitrile, acetone, 2-methyltetrahydrofuran) or a solvent mixture (2-methyltetrahydrofuran saturated with water; water saturated with 2- methyltetrahydrofuran) in an HPLC vial. The sample was stirred at ambient temperature (about 20 to about 25 °C) overnight (about 14 h). The solution was then separated from the solid by centrifugation of the mixture in a centrifuge vial equipped with a filter. The clear solution was quantitatively diluted with methanol (MeOH) and the concentration of the solute was determined using chiral HPLC (Table 30). Table 30 – Chiral HPLC Method Auto sampler temp.: 4 °C Column: ChiralPak IE-3 (150 x 4.6 mm)
Figure imgf000088_0001
[335] Solubility data for crystalline (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2H]-2,6-piperidinedione (Form I) and the corresponding deuterated and protonated racemates in various solvents are shown in Table 31. An increased solubility was observed for crystalline (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (Form I) compared to the protonated and deuterated racemates. Attorney Docket No. SLU-030WO Table 31 – Solubility of Crystalline (S)-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2H]-2,6-piperidinedione (Form I, D-S-Enantiomer) Compared to Crystalline RS-3-(5-Amino- 2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione (D-Racemate) and Crystalline RS-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione (H- Racemate) Solubility (mg/mL) Solvent D-S-Enantiomer D-Racemate H-Racemate MeOH: methylte
Figure imgf000089_0001
[336] The solubility of crystalline Forms I, II, III, and X of the free base of (S)-3-(5-amino- 2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione was compared (water, 20°C). As shown in Table 32, the solubility of the free base of (S)-3-(5-amino-2-methyl-4- oxo-3H-quinazolin-3-yl)-[3-2H]-2,6-piperidinedione is essentially independent of the crystal form. Table 32 – Solubility of Crystalline Forms of (S)-3-(5-Amino-2-methyl-4-oxo-3H- quinazolin-3-yl)-[3-2H]-2,6-piperidinedione in Water at 20°C Crystal Form Solubility (mg/mL)
Figure imgf000089_0002
Attorney Docket No. SLU-030WO Example 5: Pharmacokinetic (PK) Studies [337] The objectives of the pharmacokinetic (PK) studies were to evaluate and compare the PK profiles of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione (formula I, deuterated (S)-enantiomer, d-S) and RS-3-(5-amino-2-methyl-4- oxo-3H-quinazolin-3-yl)-2,6-piperidinedione (protonated racemate, h-rac) after single dose administration by the oral route to mice, rats, and nonhuman primates. Mouse PK [338] Female CB.17 severe combined immunodeficiency (SCID) mice (8-12 weeks of age) were administered a single dose of protonated racemate (h-rac, 30 mg/kg) or deuterated (S)- enantiomer (d-S, 15 mg/kg; containing about 10% of the protonated enantiomer) by oral gavage. Both compounds were formulated in a 0.5% w/v solution of hydroxypropylmethylcellulose in water at 3 and 1.5 mg/mL for h-rac and d-S, respectively. Plasma was obtained from N = 3 per group per time point at 0.25, 0.5, 1, 2, 4, 8, and 24 h post-dose. Plasma samples were prepared for quantitative analysis by liquid-liquid extraction in MTBE with ondansetron as internal standard (ISTD). MTBE was evaporated under a nitrogen flow and the residues were reconstituted in a 1% v/v acetic acid solution in water and acetonitrile (20:80 v/v). Analysis was performed by chiral liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS) on a Daicel ChiralPak IE-3 column using an isocratic LC method (eluent: 0.1% (v/v) acetic acid in a 20:80 v/v mix of water and acetonitrile). ISTD-normalized peak areas for the deuterated enantiomers were corrected from interference from naturally occurring isotopes of the protonated analytes. Concentrations were obtained by interpolation on standard curves prepared in mouse plasma using standard solutions of the analytes. Data was plotted in Excel 2013 (Microsoft Corp, Redmond, WA) and analyzed within Excel using the PKSolver add-in (version 2.0, as described in Zhang Y. et al Comput. Methods Programs Biomed.99 (2010), 306-314) to determine PK parameters including exposure (as area under the curve, AUC) and elimination half-life (t1/2). PK profiles are shown in FIG.27 and selected PK parameters are presented in Table 34. Attorney Docket No. SLU-030WO Table 34 – Mouse PK Parameters (area under the curve, AUC, and elimination half-life, t1/2) After a Single Oral Dose of (S)-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione (d-S) or RS-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6- piperidinedione (h-rac) Compound h-rac d-S Dose (mg/kg) 30 15 where h-S, h-R,
Figure imgf000091_0001
and (R)- enantiomers of 3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione while h- rac is the protonated racemate of the same compound (i.e., the 1:1 mixture of the protonated (R)- and (S)-enantiomers) [339] After dosing of the protonated racemate, exposure to enantiomers h-S and h-R is stereoselective with h-S representing about 39% of the total exposure. Exposure to protonated enantiomers h-S and h-R upon administration of d-S represents about 14% of the total exposure, very similar to the amount of protonated compound in the dosed material. Little to no deuterium/hydrogen (D/H) exchange is evidenced in the PK parameters after dosing d-S and exposure to the dosed enantiomer (h-S + d-S) represents about 96% of the total exposure. Finally, exposure to the dosed enantiomer after dosing d-S is about twice the exposure to the same enantiomer after dosing h-rac at twice the dose, indicating increased bioavailability of d-S vs. h-rac. Rat PK [340] Male Sprague-Dawley (SD) rats (6-8 weeks of age), fasted overnight, were administered a single dose of protonated racemate (h-rac, 300 mg/kg) or deuterated (S)- enantiomer (d-S, 150 mg/kg) by oral gavage (each formulated in a solution of 0.5% Attorney Docket No. SLU-030WO carboxymethylcellulose and 0.25% polysorbate 80 solution in water). Plasma was obtained from N = 3 animals per group by serial bleeding at 0.0833, 0.25, 0.5, 1, 2, 4, 8, and 24 h post- dose. Samples suitable for quantitative analysis by LC/MS-MS were prepared by protein precipitation with warfarin as the ISTD. LC/MS-MS sample analysis was performed by elution of a 1µL sample on a Daicel ChiralPak IE-3 column (4.6 x 150 mm, 3µm) using an isocratic method (eluent: 80:20 mix of 0.1% (v/v) formic acid in water and acetonitrile; 0.7 mL/min) followed by detection by MS-MS. ISTD-normalized peak areas for the deuterated enantiomer were corrected from interference from naturally occurring isotopes of the corresponding protonated analyte if present in the same samples. Concentrations of the deuterated and protonated enantiomers were obtained by interpolation on standard curves prepared in rat plasma using standard solutions of the analytes. Data was plotted in Excel version 2208 (Microsoft Corp, Redmond, WA) and analyzed in Phoenix WinNonlin version 8.3 (Certara LP, Princeton, NJ, USA) with a non-compartmental method to determine PK parameters including exposure (as area under the curve, AUC) and elimination half-life (t1/2). PK profiles are shown in FIG.28 and selected PK parameters are presented in Table 35. Table 35 – Rat PK Parameters (area under the curve, AUC, and elimination half-life, t1/2) After a Single Oral Dose of (S)-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]-2,6- piperidinedione (d-S) or RS-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6- piperidinedione (h-rac) compound h-rac d-S where h-
Figure imgf000092_0001
, , (S)- enantiomers of 3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione while h- rac is the protonated racemate of the same compound. Attorney Docket No. SLU-030WO [341] As in mouse, after administration of h-rac, exposure to enantiomers h-S and h-R is stereoselective with h-S representing about 41% of the total exposure. Exposure to protonated enantiomers h-S and h-R upon administration of d-S represents about 14% of the total exposure, very similar to the amount of protonated compound in the dosed material. Little to no D/H exchange is evidenced in the PK parameters after dosing d-S and exposure to the dosed enantiomer (h-S + d-S) represents about 95% of the total exposure. Finally, exposure to the dosed enantiomer after dosing d-S is about 4.8 times the exposure to the same enantiomer after dosing h-rac at twice the dose, indicating increased bioavailability of d-S vs. h-rac. Monkey PK [342] Cynomolgus monkeys (2.5 to 6 years of age, 3 males and 3 females), fasted overnight, were administered by oral gavage a single dose of the protonated racemate (h-rac, 1.5 mg/kg) followed by the deuterated (S)-enantiomer (d-S, 0.25 and 0.75 mg/kg). Both h-rac and d-S were formulated in a 0.5% carboxymethylcellulose, 0.25% polysorbate 80 solution in water. Administration of each dose level of d-S was performed after a 7-day washout period. Plasma was obtained from all animals after each dosing by serial bleeding pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12, and 24 h post-dose. Samples suitable for quantitative analysis by LC/MS-MS were prepared by protein precipitation with warfarin as the ISTD. LC/MS-MS sample analysis was performed by elution of a 5µL sample on a Daicel ChiralPak IE-3 column (4.6 x 150 mm, 3µm) using an isocratic method (eluent: 80:20 mix of 0.1% (v/v) formic acid in water and acetonitrile; 0.7 mL/min) followed by detection by MS-MS. ISTD- normalized peak areas for the deuterated enantiomer were corrected from interference from naturally occurring isotopes of the corresponding protonated analyte if present in the same samples. Concentrations of the deuterated and protonated enantiomers were obtained by interpolation on standard curves prepared in monkey plasma using standard solutions of the analytes. Data was plotted in Excel version 2208 (Microsoft Corp, Redmond, WA) and analyzed in Phoenix WinNonlin version 8.3 (Certara LP, Princeton, NJ, USA) with a non- compartmental method to determine PK parameters including exposure (as area under the curve, AUC) and elimination half-life (t1/2). PK profiles are shown in FIG.29 and selected PK parameters are presented in Table 36. Attorney Docket No. SLU-030WO Table 36 – Monkey PK Parameters (area under the curve, AUC, and elimination half-life, t1/2) After a Single Oral Dose of (S)-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-2H]- 2,6-piperidinedione (d-S) or RS-3-(5-Amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6- piperidinedione (h-rac) compound h-rac d-S Dose (mg/kg) 1.5 0.25 0.75
Figure imgf000094_0001
enantiomers of 3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione while h- rac is the protonated racemate of the same compound (N/A: not applicable; NC: not calculated). [343] As in mouse and rat, exposure to enantiomers h-S and h-R of h-rac is stereoselective with h-S representing about 40% of the total exposure. Exposure to protonated enantiomers h-S and h-R upon administration of d-S represents about 10-14% of the total exposure, very similar to the amount of protonated compound in the dosed material. Little to no D/H exchange is evidenced in the PK parameters after dosing d-S and exposure to the dosed enantiomer (h-S + d-S) represents about 95-100% of the total exposure. The exposure to the dosed enantiomer after dosing d-S is similar to the exposure to the same enantiomer after dosing h-rac at twice the dose (2573 vs.2880 h.ng/mL, for d-S and h-rac dosing, respectively). Interestingly, the elimination half-lives of d-S and h-S after dosing d-S are about one half of the elimination half-life of h-S after dosing h-rac while the elimination half- life of h-R is similar. Additionally, the concentrations of d-S and h-S after dosing d-S reach Attorney Docket No. SLU-030WO their maximum (Cmax) about 2 times earlier than h-S after dosing h-rac, as shown by the differences in Tmax, and the combined Cmax of d-S and h-S after dosing d-S is about 2-fold larger than the Cmax of h-S after dosing h-rac (474 vs.267 ng/mL for d-S+h-S after dosing d- S and h-S after dosing h-rac, respectively). INCORPORATION BY REFERENCE [344] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present disclosure that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the disclosure can be excluded from any claim, for any reason, whether or not related to the existence of prior art. EQUIVALENTS [345] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

Attorney Docket No. SLU-030WO CLAIMS We claim: 1. A crystalline form of the compound of formula (I) N CH3 .
Figure imgf000096_0001
2. The crystalline form of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 11.0° 2θ. 3. The crystalline form of claim 1, wherein the crystalline form of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 11.9° 2θ. 4. The crystalline form of claim 1, wherein the crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. 5. The crystalline form of any one of claims 1-4, wherein the crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 11.0°, about 11.9°, and about 14.1° 2θ. 6. The crystalline form of any one of claims 2-5, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.7°, about 21.1°, about 21.5°, about 23.5°, about 24.0°, and about 24.7° 2θ. 7. The crystalline form of any one of claims 2-6, wherein the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.9°, about 29.2°, about 31.1°, about 32.5°, about 33.7°, and about 34.5° 2θ. Attorney Docket No. SLU-030WO 8. The crystalline form of any one of claims 2-7, wherein about means ± 0.3° 2θ. 9. The crystalline form of any one of claims 2-7, wherein about means ± 0.2° 2θ. 10. The crystalline form of any one of claims 1-9, wherein the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1. 11. The crystalline form of any one of claims 1-9, wherein the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. 12. The crystalline form of any one of claims 1-9, wherein the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.10. 13. The crystalline form of any one of claims 1-9, wherein the crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.2. 14. The crystalline form of any one of claims 1-12, wherein the crystalline form of the compound of formula (I) is an anhydrous crystalline form. 15. The crystalline form of any one of claims 1-9 and 13, wherein the crystalline form of the compound of formula (I) is a crystalline hydrate. 16. An anhydrous crystalline form of the compound of formula (I) .
Figure imgf000097_0001
17. The anhydrous crystalline form of claim 16, wherein the anhydrous crystalline form of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.9° 2θ. Attorney Docket No. SLU-030WO 18. The anhydrous crystalline form of claim 16, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. 19. The anhydrous crystalline form of claim 16, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. 20. The anhydrous crystalline form of any one of claims 16-19, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.9°, about 11.9°, and about 14.1° 2θ. 21. The anhydrous crystalline form of any one of claims 17-20, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 18.7°, about 19.7°, about 21.2°, about 21.6°, about 23.3°, about 24.1°, and about 24.6° 2θ. 22. The anhydrous crystalline form of any one of claims 17-21, wherein the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.8°, about 29.2°, about 30.6°, about 31.1°, about 32.4°, about 33.0°, about 33.8°, and about 34.7° 2θ. 23. The anhydrous crystalline form of any one of claims 17-22, wherein about means ± 0.3° 2θ. 24. The anhydrous crystalline form of any one of claims 17-22, wherein about means ± 0.2° 2θ. 25. The anhydrous crystalline form of any one of claims 16-24, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.1. 26. The anhydrous crystalline form of any one of claims 16-24, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. Attorney Docket No. SLU-030WO 27. The anhydrous crystalline form of any one of claims 16-24, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.10. 28. Form I of a compound of formula (I) N CH3 .
Figure imgf000099_0001
29. The Form I of the Form I of the compound of formula (I) is an anhydrous crystalline form. 30. The Form I of the compound of formula (I) of claim 28 or 29, wherein Form I of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.3° 2θ. 31. The Form I of the compound of formula (I) of claim 28 or 29, wherein Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.0° 2θ. 32. The Form I of the compound of formula (I) of claim 28 or 29, wherein Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. 33. The Form I of the compound of formula (I) of claim 28 or 29, wherein Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.7° 2θ. 34. The Form I of the compound of formula (I) of claim 28 or 29, wherein Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.0° 2θ. 35. The Form I of the compound of formula (I) of claim 28 or 29, wherein Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.8° 2θ. Attorney Docket No. SLU-030WO 36. The Form I of the compound of formula (I) of any one of claims 28-35, wherein Form I of the compound of formula (I) has an XRPD pattern comprising one or more peaks selected from about 10.3°, about 11.0°, about 11.9°, about 13.7°, about 14.0°, and about 14.8° 2θ. 37. The Form I of the compound of formula (I) of any one of claims 29-36, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 17.4°, about 20.6°, about 21.1°, about 23.2°, and about 24.1° 2θ. 38. The Form I of the compound of formula (I) of any one of claims 29-37, wherein the XRPD pattern further comprises one or more peaks selected from about 17.6°, about 18.7°, about 19.7°, about 21.6°, about 23.0°, about 23.7°, and about 24.6° 2θ. 39. The Form I of the compound of formula (I) of any one of claims 29-38, wherein the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.8°, about 28.2°, about 30.3°, about 30.5°, and about 33.0° 2θ. 40. The Form I of the compound of formula (I) of any one of claims 29-39, wherein the XRPD pattern further comprises one or more peaks selected from about 25.6°, about 27.1°, about 28.9°, about 29.2°, about 30.9°, about 31.1°, about 32.1°, about 32.4°, about 33.8°, about 34.0°, about 34.5°, and about 34.7° 2θ. 41. The Form I of the compound of formula (I) of any one of claims 30-40, wherein about means ± 0.3° 2θ. 42. The Form I of the compound of formula (I) of any one of claims 30-40, wherein about means ± 0.2° 2θ. 43. The Form I of the compound of formula (I) of any one of claims 28-42, wherein Form I of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG. 1A. Attorney Docket No. SLU-030WO 44. The Form I of the compound of formula (I) of any one of claims 28-43, wherein Form I of the compound of formula (I) has a differential scanning calorimetry (DSC) thermogram comprising one or more endotherms with peak onsets at about 238 °C and about 273.9 °C. 45. The Form I of the compound of formula (I) of any one of claims 28-44, wherein Form I of the compound of formula (I) has a DSC thermogram substantially the same as shown in FIG.20. 46. The Form I of the compound of formula (I) of any one of claims 28-45, wherein Form I of the compound of formula (I) exhibits a change in mass of less than or equal to about 3% wt when varying the relative humidity between 0% and about 80%. 47. The Form I of the compound of formula (I) of any one of claims 28-46, wherein Form I of the compound of formula (I) has a water sorption isotherm substantially the same as shown in FIG.21. 48. Form III of a compound of formula (I) N CH3 .
Figure imgf000101_0001
49. The Form III of the compound of formula (I) of claim 48, wherein Form III of the compound of formula (I) is an anhydrous crystalline form. 50. The Form III of the compound of formula (I) of claim 48 or 49, wherein Form III of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.7° 2θ. 51. The Form III of the compound of formula (I) of claim 48 or 49, wherein Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9° 2θ. Attorney Docket No. SLU-030WO 52. The Form III of the compound of formula (I) of claim 48 or 49, wherein Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. 53. The Form III of the compound of formula (I) of claim 48 or 49, wherein Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.2° 2θ. 54. The Form III of the compound of formula (I) of claim 48 or 49, wherein Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.3° 2θ. 55. The Form III of the compound of formula (I) of claim 48 or 49, wherein Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ. 56. The Form III of the compound of formula (I) of any one of claims 48-55, wherein Form III of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, and about 14.3° 2θ. 57. The Form III of the compound of formula (I) of any one of claims 50-56, wherein the XRPD pattern further comprises one or more peaks selected from about 15.1°, about 19.0°, about 19.3°, about 21.8°, and about 24.9° 2θ. 58. The Form III of the compound of formula (I) of any one of claims 50-57, wherein the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, and about 24.7° 2θ. 59. The Form III of the compound of formula (I) of any one of claims 50-58, wherein the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 29.1°, about 32.3°, about 32.5°, about 33.1°, and about 34.1° 2θ. 60. The Form III of the compound of formula (I) of any one of claims 50-58, wherein the XRPD pattern further comprises one or more peaks selected from about 27.7°, about 28.3°, Attorney Docket No. SLU-030WO about 28.6°, about 28.8°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.8°, about 33.6°, about 33.8°, about 34.3°, and about 34.5° 2θ. 61. The Form III of the compound of formula (I) of any one of claims 50-60, wherein about means ± 0.3° 2θ. 62. The Form III of the compound of formula (I) of any one of claims 50-60, wherein about means ± 0.2° 2θ. 63. The Form III of the compound of formula (I) of any one of claims 48-62, wherein Form III of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.3. 64. Form X of a compound of formula (I) N CH3 .
Figure imgf000103_0001
65. The Form X of the compound of formula (I) of claim 64, wherein Form X of the compound of formula (I) is an anhydrous crystalline form. 66. The Form X of the compound of formula (I) of claim 64 or 65, wherein Form X of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.6° 2θ. 67. The Form X of the compound of formula (I) of claim 64 or 65, wherein Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9° 2θ. 68. The Form X of the compound of formula (I) of claim 64 or 65, wherein Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.0° 2θ. Attorney Docket No. SLU-030WO 69. The Form X of the compound of formula (I) of claim 64 or 65, wherein Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. 70. The Form X of the compound of formula (I) of claim 64 or 65, wherein Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.5° 2θ. 71. The Form X of the compound of formula (I) of any one of claims 64-70, wherein Form X of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.6°, about 10.9°, about 12.0°, about 14.1°, and about 14.5° 2θ. 72. The Form X of the compound of formula (I) of any one of claims 66-71, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.1°, about 21.9°, and about 24.1° 2θ. 73. The Form X of the compound of formula (I) of any one of claims 66-72, wherein the XRPD pattern further comprises one or more peaks selected from about 17.5°, about 18.0°, about 18.8°, about 19.7°, about 20.7°, about 21.2°, about 21.6°, about 22.3°, about 23.3°, and about 24.6° 2θ. 74. The Form X of the compound of formula (I) of any one of claims 66-73, wherein the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 27.3°, about 29.0°, about 29.2°, about 30.8°, and about 31.1° 2θ. 75. The Form X of the compound of formula (I) of any one of claims 66-74, wherein the XRPD pattern further comprises one or more peaks selected from about 25.8°, about 26.4°, about 28.7°, about 30.6°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2θ. 76. The Form X of the compound of formula (I) of any one of claims 66-75, wherein about means ± 0.3° 2θ. Attorney Docket No. SLU-030WO 77. The Form X of the compound of formula (I) of any one of claims 66-75, wherein about means ± 0.2° 2θ. 78. The Form X of the compound of formula (I) of any one of claims 64-77, wherein Form X of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.10. 79. The Form X of the compound of formula (I) of any one of claims 64-78, wherein Form X of the compound of formula (I) has a differential scanning calorimetry (DSC) thermogram comprising one or more endotherms with peak onsets at about 235.8 °C and about 281.9 °C. 80. The Form X of the compound of formula (I) of any one of claims 64-79, wherein Form X of the compound of formula (I) has a DSC thermogram substantially the same as shown in FIG.22. 81. The Form X of the compound of formula (I) of any one of claims 64-80, wherein Form X of the compound of formula (I) exhibits a change in mass of less than or equal to about 3% wt when varying the relative humidity between 0% and about 80%. 82. The Form X of the compound of formula (I) of any one of claims 64-81, wherein Form X of the compound of formula (I) has a water sorption isotherm substantially the same as shown in FIG.23. 83. A crystalline hydrate of the compound of formula (I) .
Figure imgf000105_0001
84. The crystalline hydrate of claim 83, wherein the crystalline hydrate is a crystalline monohydrate. Attorney Docket No. SLU-030WO 85. Form II of a compound of formula (I) . 86. The Form II of the
Figure imgf000106_0001
Form II of the compound of formula (I) is a crystalline hydrate. 87. The Form II of the compound of formula (I) of claim 85 or 86, wherein Form II of the compound of formula (I) is a crystalline monohydrate. 88. The Form II of the compound of formula (I) of any one of claims 85-87, wherein Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 6.9° 2θ. 89. The Form II of the compound of formula (I) of any one of claims 85-87, wherein Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.2° 2θ. 90. The Form II of the compound of formula (I) of any one of claims 85-87, wherein Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.7° 2θ. 91. The Form II of the compound of formula (I) of any one of claims 85-87, wherein Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.9° 2θ. 92. The Form II of the compound of formula (I) of any one of claims 85-87, wherein Form II of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ. 93. The Form II of the compound of formula (I) of any one of claims 85-92, wherein Form II of the compound of formula (I) has an XRPD pattern comprising peaks at about 6.9°, about 11.2°, about 11.7°, about 13.9°, and about 14.3° 2θ. Attorney Docket No. SLU-030WO 94. The Form II of the compound of formula (I) of any one of claims 88-93, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 15.5°, about 17.4°, about 20.9°, about 22.3°, and about 23.6° 2θ. 95. The Form II of the compound of formula (I) of any one of claims 88-94, wherein the XRPD pattern further comprises one or more peaks selected from about 17.9°, about 19.7°, about 21.4°, about 22.8°, about 23.8°, and about 24.9° 2θ. 96. The Form II of the compound of formula (I) of any one of claims 88-95, wherein the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, and about 28.8° 2θ. 97. The Form II of the compound of formula (I) of any one of claims 88-96, wherein the XRPD pattern further comprises one or more peaks selected from about 28.6°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2θ. 98. The Form II of the compound of formula (I) of any one of claims 88-97, wherein about means ± 0.3° 2θ. 99. The Form II of the compound of formula (I) of any one of claims 88-97, wherein about means ± 0.2° 2θ. 100. The Form II of the compound of formula (I) of any one of claims 85-99, wherein Form II of the compound of formula (I) has an XRPD pattern substantially the same as shown in FIG.2. 101. A pharmaceutical composition comprising: (i) a crystalline form of a compound of formula (I) Attorney Docket No. SLU-030WO (ii) a
Figure imgf000108_0001
102. The pharmaceutical composition of claim 101, wherein the crystalline form of a compound of formula (I) is the crystalline form of a compound of formula (I) of any one of claims 1-15. 103. A pharmaceutical composition comprising: (i) an anhydrous crystalline form of a compound of formula (I) (ii) a
Figure imgf000108_0002
104. The pharmaceutical composition of claim 103, wherein the anhydrous crystalline form of a compound of formula (I) is the anhydrous crystalline form of a compound of formula (I) of any one of claims 16-27. 105. A pharmaceutical composition comprising: (i) a crystalline hydrate of a compound of formula (I) (ii) a
Figure imgf000108_0003
Attorney Docket No. SLU-030WO 106. The pharmaceutical composition of claim 105, wherein the crystalline hydrate of a compound of formula (I) is the crystalline hydrate of a compound of formula (I) of claim 83 or 84. 107. A pharmaceutical composition comprising: (i) the Form I of a compound of formula (I) of any one of claims 28-47, the Form II of a compound of any one of claims 85-100, the Form III of a compound of formula (I) of any one of claims 48-63, or the Form X of a compound of formula (I) of any one of claims 64-82 (ii) a
Figure imgf000109_0001
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014110558A1 (en) * 2013-01-14 2014-07-17 Deuterx, Llc 3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives
WO2018165142A1 (en) * 2017-03-07 2018-09-13 Celgene Corporation Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014110558A1 (en) * 2013-01-14 2014-07-17 Deuterx, Llc 3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives
WO2018165142A1 (en) * 2017-03-07 2018-09-13 Celgene Corporation Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
"Physicians' Desk Reference", 2006
"Remington: The Science and Practice of Pharmacy", 2005, LIPPINCOTT WILLIAMS & WILKINS
"Remington's Pharmaceutical Sciences", 1990, MACK PUBLISHING
C. F. MACRAE ET AL., J. APPL. CRYST., vol. 53, 2020, pages 226 - 235
C-H GU ET AL: "Physical Properties and Crystal Structures of Chiral Drugs", 1 January 2003, STEREOCHEMICAL ASPECTS OF DRUG ACTION AND DISPOSITION - HANDBOOK OF EXPERIMENTAL PHARMACOLOGY,, PAGE(S) 113 - 139, XP009179283 *
JACQUES ET AL., PROC NATL ACAD SCI U.S.A., vol. 112, 2015, pages E1471 - E1479
ZHANG Y. ET AL., COMPUT. METHODS PROGRAMS BIOMED., vol. 99, 2010, pages 306 - 314

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