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WO2024148164A1 - Formes solides et méthodes d'utilisation - Google Patents

Formes solides et méthodes d'utilisation 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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English (en)
Inventor
Sheila Dewitt
Vincent Jacques
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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 AU2024206378A priority Critical patent/AU2024206378A1/en
Priority to JP2025540139A priority patent/JP2026501784A/ja
Priority to EP24705274.9A priority patent/EP4646407A1/fr
Publication of WO2024148164A1 publication Critical patent/WO2024148164A1/fr
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

La présente invention concerne des formes cristallines du composé de formule (I) et des compositions associées. (I)
PCT/US2024/010321 2023-01-06 2024-01-04 Formes solides et méthodes d'utilisation Ceased WO2024148164A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014110558A1 (fr) * 2013-01-14 2014-07-17 Deuterx, Llc Dérivés de 3-(5-substituté-4-oxoquinazolin-3(4h)-yl)-3-deutéro-pipéridine-2,6-dione
WO2018165142A1 (fr) * 2017-03-07 2018-09-13 Celgene Corporation Formes solides de 3-(5-amino-2-méthyl-4-oxo-4h-quinazolin-3-yl)-pipéridine-2,6-dione, leurs compositions pharmaceutiques et leurs utilisations

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WO2014110558A1 (fr) * 2013-01-14 2014-07-17 Deuterx, Llc Dérivés de 3-(5-substituté-4-oxoquinazolin-3(4h)-yl)-3-deutéro-pipéridine-2,6-dione
WO2018165142A1 (fr) * 2017-03-07 2018-09-13 Celgene Corporation Formes solides de 3-(5-amino-2-méthyl-4-oxo-4h-quinazolin-3-yl)-pipéridine-2,6-dione, leurs compositions pharmaceutiques et leurs utilisations

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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 *
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