# US 11,306,080 B2 · Crystalline form of a BACE inhibitor, compositions, and use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,080 B2 - Document ID: US11306080B2 - Status: Granted - Kind: B2 - Application number: 16/622,323 - Filed: 2018-06-08 - Published: 2020-06-25 - Granted: 2022-04-19 - Earliest claimed: 2017-06-13 - Assignees: Merck Sharp & Dohme Corp. - Applicants: Merck Sharp & Dohme Corp.; Laura M. Artino; William Morris; Eric Sirota; Richard J. Varsolona - Inventors: Laura M. Artino; William Morris; Eric Sirota; Richard J. Varsolona - Web page: https://patentgrep.com/patent/US11306080B2 ## CPC - C07D 417/12: linked by a chain containing hetero atoms as chain links - C07C 309/30: of six-membered aromatic rings substituted by alkyl groups - C07B 2200/13: Crystalline forms, e.g. polymorphs - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract The present invention provides a novel crystalline form of verubecestat (Crystalline Form II of Verubecestat) and pharmaceutically acceptable compositions thereof, each of which may be useful in treating, preventing, ameliorating, and/or delaying the onset of an Aβ pathology and/or a symptom or symptoms thereof. Non-limiting examples of such Aβ pathologies, including Alzheimer's disease and mild cognitive impairment, are disclosed herein. ## Claims ### Claim 1 A crystalline form of verubecestat characterized by a powder x-ray diffraction pattern with at least peaks at diffraction angles degrees 2 theta (+/−0.2°) of 10.94 and 14.98 in a powder x-ray diffraction obtained using Cu K alpha radiation. ### Claim 2 (depends on 1) The crystalline form of verubecestat according to claim 1, characterized by a powder x-ray diffraction pattern with at least peaks at diffraction angles degrees 2 theta (+/−0.2°) of 10.94, 14.53, 14.98, 16.23, 16.63, and 26.18. ### Claim 3 (depends on 2) The crystalline form of verubecestat according to claim 2, characterized by a powder x-ray diffraction pattern with at least peaks at diffraction angles degrees 2 theta (+/−0.2°) of 10.94, 14.53, 14.98, 16.23, 16.63, 17.77, 21.77, 23.24, and 26.18. ### Claim 4 (depends on 3) The crystalline form of verubecestat according to claim 3, characterized by a powder x-ray diffraction pattern with at least peaks at diffraction angles degrees 2 theta (+/−0.2°) of 10.94, 14.53, 14.98, 16.23, 16.63, 17.77, 20.84, 21.77, 23.24, 26.18, 30.88, and 33.39. ### Claim 5 (depends on 4) The crystalline form of verubecestat according to claim 4 characterized by substantially the same powder x-ray diffraction pattern as shown in FIG. 1. ### Claim 6 (depends on 1) The crystalline form of verubecestat of claim 1 exhibiting a melting endotherm with a peak temperature at 183.5° C. (+/−1° C.), measured by differential scanning calorimetry. ### Claim 7 (depends on 6) A crystalline form of verubecestat according to claim 6 exhibiting a melting endotherm with an extrapolated onset temperature of 181.7° C. (+/−1° C.) and a peak temperature at 183.5° C. (+/−1° C.), measured by differential scanning calorimetry. ### Claim 8 (depends on 6) The crystalline form of verubecestat according to claim 6 that exhibits a melting point substantially the same as shown in the differential scanning calorimetry scan of FIG. 2. ### Claim 9 (depends on 1) The crystalline form of verubecestat of claim 1 having a solid state 13C NMR spectrum exhibiting any two of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 10 (depends on 9) The crystalline form of verubecestat according to claim 9 having a solid state 13C NMR spectrum exhibiting any three of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 11 (depends on 9) The crystalline form of verubecestat according to claim 9 having a solid state 13C NMR spectrum exhibiting any four of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 12 (depends on 9) The crystalline form of verubecestat according to claim 9 having a solid state 13C NMR spectrum exhibiting any five of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 13 (depends on 9) The crystalline form of verubecestat according to claim 9 having a solid state 13C NMR spectrum exhibiting the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 14 (depends on 9) The crystalline form of verubecestat according to claim 9 having a solid state 13C NMR substantially as shown in FIG. 4. ### Claim 15 (depends on 1) The crystalline form of verubecestat of claim 1 having an ORTEP representation as shown in FIG. 5. ### Claim 16 (depends on 1) The crystalline form of verubecestat according to claim 1 further characterized as exhibiting a peak temperature at 183.5° C. (+/−1° C.), measured by differential scanning calorimetry. ### Claim 17 (depends on 16) The crystalline form of verubecestat according to claim 16, further characterized as exhibiting a melting endotherm with an extrapolated onset temperature of 181.7° C. (+/−1° C.) and a peak temperature at 183.5° C. (+/−1° C.), measured by differential scanning calorimetry. ### Claim 18 (depends on 1) The crystalline form of verubecestat according to claim 1, further characterized by a solid state 13C NMR spectrum exhibiting any two of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 19 (depends on 16) The crystalline form of verubecestat according to claim 16, further characterized by a solid state 13C NMR spectrum exhibiting any two of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 20 (depends on 17) The crystalline form of verubecestat according to claim 17, further characterized by a solid state 13C NMR spectrum exhibiting any two of the following peaks: 162.98, 160.46, 158.65, 156.39, 151.47, 145.63, 139.21, 133.72, 132.28, 125.50, 124.38, 122.10, 114.93, 57.11, 55.82, 29.22 and 25.66 ppm. ### Claim 21 (depends on 1) The crystalline form of verubecestat according to claim 1, further having a ORTEP representation as shown in FIG. 5.