# US 2025/0368606 A1 · Crystalline forms and salt forms of a kinase inhibitor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0368606 A1 - Document ID: US20250368606A1 - Status: Published application - Kind: A1 - Application number: 18/723,013 - Filed: 2022-12-22 - Published: 2025-12-04 - Earliest claimed: 2021-12-22 - Assignees: Exelixis, Inc. - Applicants: Exelixis, Inc. - Inventors: Kirsten PHIZACKERLEY; Yizheng CAO; Dominika PCION - Web page: https://patentgrep.com/patent/US20250368606A1 ## CPC - C07D 215/48: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen - A61P 35/00: Antineoplastic agents - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to crystalline free base of the tyrosine kinase inhibitor, Compound 1. The invention also relates to crystalline salts of Compound 1. The invention also relates to pharmaceutical compositions comprising the solid polymorphs of the free base and salts of Compound 1. The invention further relates to methods of treating a disease, disorder, or syndrome mediated at least in part by modulating in vivo activity of a protein kinase. ## Claims ### Claim 1 A crystalline solid of Compound 1 wherein the crystalline solid of Compound 1 is selected from Compound 1 Form R, Compound 1 Form S, Compound 1 Form T, Compound 1 Form U, Compound 1 Form V, Compound 1 Form W, Compound 1 Form X, Compound 1 Form Y, and mixtures thereof. ### Claim 2 (canceled) ### Claim 3 (depends on 1) The crystalline solid of claim 1, wherein Compound 1 Form R is characterized by an XRPD pattern comprising one or more peaks selected from 4.65, 5.33, 6.55, 7.56, 9.31, 10.69, 11.38, 14.63, 15.17, 15.74, 16.09, 16.41, 16.51, 17.05, 17.39, 17.93, 18.24, 18.78, 19.24, 19.93, 20.15, 20.71, 21.44, 22.22, 22.66, 22.99, 23.39, 24.06, 24.38, 24.70, 25.75, 26.15, 26.48, 27.05, 27.24, 27.54, 27.88, and 28.71 degrees 2θ (±0.2 degrees); Form S is characterized by an XRPD pattern comprising one or more peaks selected from 5.56, 8.37, 11.22, 12.49, 12.83, 13.69, 16.85, 17.60, 17.98, 18.69, 19.62, 20.11, 20.70, 21.03, 21.65, 21.89, 22.90, 23.79, 24.58, 25.12, 25.89, 26.20, 26.94, 27.43, 28.15, 29.73, and 30.22 degrees 2θ (±0.2 degrees); Form T is characterized by an XRPD pattern comprising one or more peaks selected from 7.15, 8.92, 9.59, 10.56, 11.20, 12.29, 13.44, 13.87, 14.31, 15.72, 16.85, 17.48, 17.95, 18.27, 18.48, 19.36, 21.16, 21.58, 22.02, 22.52, 23.34, 24.74, 25.97, 26.41, 27.01, 27.47, 28.66, 29.07, 29.43, and 30.25 degrees 2θ (±0.2 degrees); Compound 1 Form U is characterized by an XRPD pattern comprising one or more peaks selected from 6.12, 8.64, 9.24, 9.66, 10.62, 11.48, 12.27, 13.06, 13.70, 14.34, 14.70, 16.05, 17.04, 17.34, 17.72, 18.61, 18.96, 19.43, 19.57, 20.08, 20.25, 20.98, 21.25, 21.43, 22.23, 22.39, 22.83, 23.23, 23.62, 23.97, 24.89, 25.70, 26.21, 26.48, 27.35, 27.94, 28.22, 28.55, 28.93, 29.27, 29.45, 29.85, 29.98, and 30.24 degrees 2θ (±0.2 degrees); Compound 1 Form V is characterized by an XRPD pattern comprising one or more peaks selected from 6.05, 9.21, 9.66, 10.45, 11.45, 11.58, 12.14, 12.29, 12.86, 13.62, 14.32, 16.08, 16.86, 17.40, 17.66, 18.26, 18.45, 18.79, 19.31, 19.41, 20.28, 20.98, 21.36, 21.54, 21.85, 22.23, 22.45, 22.78, 23.00, 23.34, 23.96, 24.90, 25.69, 25.90, 26.38, 27.18, 28.02, 28.25, 28.54, 29.24, and 29.89 degrees 2θ (±0.2 degrees); Compound 1 Form W is characterized by an XRPD pattern comprising one or more peaks selected from 8.82, 9.58, 10.50, 10.85, 11.21, 11.44, 11.57, 13.16, 13.22, 14.22, 14.40, 14.91, 15.81, 16.74, 17.10, 17.55, 17.95, 18.13, 18.35, 18.73, 19.16, 19.37, 19.56, 19.91, 20.65, 21.02, 21.30, 21.54, 21.84, 22.34, 22.62, 22.98, 23.27, 23.53, 24.10, 24.66, 25.08, 25.36, 25.62, 25.90, 26.41, 26.85, 27.07, 27.24, 27.70, 28.27, 28.73, 28.94, 29.25, 29.54, 30.11, and 30.53 degrees 2θ (±0.2 degrees); Compound 1 Form X is characterized by an XRPD pattern comprising one or more peaks selected from 5.34, 5.88, 9.45, 10.71, 11.84, 13.36, 15.06, 16.55, 17.99, 18.80, 21.69, 22.60, 23.59, 25.54, and 26.98 degrees 2θ (±0.2 degrees); and Compound 1 Form Y is characterized by an XRPD pattern comprising one or more peaks selected from 9.77, 10.22, 11.09, 11.60, 12.83, 13.20, 13.71, 14.57, 14.99, 16.06, 16.55, 17.43, 18.12, 18.45, 18.98, 19.17, 19.62, 19.85, 20.56, 20.78, 20.89, 21.13, 21.41, 21.59, 22.02, 22.28, 22.72, 22.93, 23.47, 24.06, 24.22, 24.54, 24.73, 25.34, 25.68, 26.01, 26.41, 27.04, 27.47, 27.78, 28.12, 28.32, 28.77, 29.41, 30.31, 31.01, 31.24, 31.54, and 32.18 degrees 2θ (±0.2 degrees). ### Claim 4 (depends on 1) The crystalline solid of claim 1, wherein the Compound 1 Form R is characterized by an XRPD pattern comprising one or more peaks selected from 10.69, 16.09, 16.41, 16.51, 17.39, 18.78, 19.24, 19.93, 21.44, 22.66, 22.99, and 26.48 degrees 2θ (±0.2 degrees); Compound 1 Form T is characterized by an XRPD pattern comprising one or more peaks selected from 10.56, 12.29, 14.31, 18.27, 19.36, 21.16, 21.58, 22.52, 24.74, 27.47, and 28.66 degrees 2θ (±0.2 degrees); Compound 1 Form U is characterized by an XRPD pattern comprising one or more peaks selected from 9.24, 10.62, 14.34, 17.04, 17.34, 17.72, 19.43, 19.57, 20.08, 20.25, 21.25, 23.23, 23.62, 23.97, and 24.89 degrees 2θ (±0.2 degrees); Compound 1 Form V is characterized by an XRPD pattern comprising one or more peaks selected from 9.21, 10.45, 14.32, 16.86, 19.31, 19.41, 20.28, 21.36, 21.54, 23.34, 23.96, 24.90, and 28.25 degrees 2θ (±0.2 degrees); Compound 1 Form W is characterized by an XRPD pattern comprising one or more peaks selected from 8.82, 11.21, 11.44, 11.57, 13.16, 13.22, 14.40, 16.74, 17.95, 18.13, 19.16, 19.37, 19.56, 19.91, 21.84, 22.98, and 24.10 degrees 2θ (±0.2 degrees); Compound 1 Form X is characterized by an XRPD pattern comprising one or more peaks selected from 5.34, 5.88, 9.45, and 10.71 degrees 2θ (±0.2 degrees); and Compound 1 Form Y is characterized by an XRPD pattern comprising one or more peaks selected from 10.22, 11.09, 11.60, 13.71, 14.57, 18.12, 19.17, 19.85, 21.41, 21.59, 23.47, 24.54, 24.73, 25.34, 28.32, and 28.77 degrees 2θ (±0.2 degrees). ### Claim 5 (depends on 1) The crystalline solid of claim 1, wherein Compound 1 Form R is characterized an XRPD pattern comprising all of the following peaks 10.69, 16.09, 16.41, 16.51, 17.39, 18.78, 19.24, 19.93, 21.44, 22.66, 22.99, and 26.48 degrees 2θ (±0.2 degrees); Compound 1 Form S is characterized by an XRPD pattern comprising all of the following peaks 8.37, 12.49, 12.83, 13.69, 16.85, 18.69, 19.62, 20.11, 20.70, 21.65, 23.79, 24.58, 25.12, and 25.89 degrees 2θ (±0.2 degrees); Compound 1 Form T is characterized by an XRPD pattern comprising all of the following peaks 10.56, 12.29, 14.31, 18.27, 19.36, 21.16, 21.58, 22.52, 24.74, 27.47, and 28.66 degrees 2θ (±0.2 degrees); Compound 1 Form U is characterized by an XRPD pattern comprising all of the following peaks 9.24, 10.62, 14.34, 17.04, 17.34, 17.72, 19.43, 19.57, 20.08, 20.25, 21.25, 23.23, 23.62, 23.97, and 24.89; Compound 1 Form V is characterized by an XRPD pattern comprising all of the following peaks 9.21, 10.45, 14.32, 16.86, 19.31, 19.41, 20.28, 21.36, 21.54, 23.34, 23.96, 24.90, and 28.25 degrees 2θ (±0.2 degrees); Compound 1 Form W is characterized by an XRPD pattern comprising all of the following peaks 8.82, 11.21, 11.44, 11.57, 13.16, 13.22, 14.40, 16.74, 17.95, 18.13, 19.16, 19.37, 19.56, 19.91, 21.84, 22.98, and 24.10 degrees 2θ (±0.2 degrees); Compound 1 Form X is characterized by an XRPD pattern comprising all of the following peaks 5.34, 5.88, 9.45, and 10.71 degrees 2θ (±0.2 degrees); and Compound 1 Form Y is characterized by an XRPD pattern comprising all of the following peaks 10.22, 11.09, 11.60, 13.71, 14.57, 18.12, 19.17, 19.85, 21.41, 21.59, 23.47, 24.54, 24.73, 25.34, 28.32, and 28.77 degrees 2θ (±0.2 degrees). ### Claim 6 (depends on 1) The crystalline solid of claim 1, wherein Compound 1 Form R is characterized an XRPD pattern comprising all of the following peaks 4.65, 5.33, 6.55, 7.56, 9.31, 10.69, 11.38, 14.63, 15.17, 15.74, 16.09, 16.41, 16.51, 17.05, 17.39, 17.93, 18.24, 18.78, 19.24, 19.93, 20.15, 20.71, 21.44, 22.22, 22.66, 22.99, 23.39, 24.06, 24.38, 24.70, 25.75, 26.15, 26.48, 27.05, 27.24, 27.54, 27.88, and 28.71 degrees 2θ (±0.2 degrees); Compound 1 Form S is characterized by an XRPD pattern comprising all of the following peaks 5.56, 8.37, 11.22, 12.49, 12.83, 13.69, 16.85, 17.60, 17.98, 18.69, 19.62, 20.11, 20.70, 21.03, 21.65, 21.89, 22.90, 23.79, 24.58, 25.12, 25.89, 26.20, 26.94, 27.43, 28.15, 29.73, and 30.22 degrees 2θ (±0.2 degrees); Compound 1 Form T is characterized by an XRPD pattern comprising all of the following peaks 7.15, 8.92, 9.59, 10.56, 11.20, 12.29, 13.44, 13.87, 14.31, 15.72, 16.85, 17.48, 17.95, 18.27, 18.48, 19.36, 21.16, 21.58, 22.02, 22.52, 23.34, 24.74, 25.97, 26.41, 27.01, 27.47, 28.66, 29.07, 29.43, and 30.25 degrees 2θ (±0.2 degrees); Compound 1 Form U is characterized by an XRPD pattern comprising all of the following peaks 6.12, 8.64, 9.24, 9.66, 10.62, 11.48, 12.27, 13.06, 13.70, 14.34, 14.70, 16.05, 17.04, 17.34, 17.72, 18.61, 18.96, 19.43, 19.57, 20.08, 20.25, 20.98, 21.25, 21.43, 22.23, 22.39, 22.83, 23.23, 23.62, 23.97, 24.89, 25.70, 26.21, 26.48, 27.35, 27.94, 28.22, 28.55, 28.93, 29.27, 29.45, 29.85, 29.98, and 30.24 degrees 2θ (±0.2 degrees); Compound 1 Form V is characterized by an XRPD pattern comprising all of the following peaks 6.05, 9.21, 9.66, 10.45, 11.45, 11.58, 12.14, 12.29, 12.86, 13.62, 14.32, 16.08, 16.86, 17.40, 17.66, 18.26, 18.45, 18.79, 19.31, 19.41, 20.28, 20.98, 21.36, 21.54, 21.85, 22.23, 22.45, 22.78, 23.00, 23.34, 23.96, 24.90, 25.69, 25.90, 26.38, 27.18, 28.02, 28.25, 28.54, 29.24, and 29.89 degrees 2θ (±0.2 degrees); Compound 1 Form W is characterized by an XRPD pattern comprising all of the following peaks 8.82, 9.58, 10.50, 10.85, 11.21, 11.44, 11.57, 13.16, 13.22, 14.22, 14.40, 14.91, 15.81, 16.74, 17.10, 17.55, 17.95, 18.13, 18.35, 18.73, 19.16, 19.37, 19.56, 19.91, 20.65, 21.02, 21.30, 21.54, 21.84, 22.34, 22.62, 22.98, 23.27, 23.53, 24.10, 24.66, 25.08, 25.36, 25.62, 25.90, 26.41, 26.85, 27.07, 27.24, 27.70, 28.27, 28.73, 28.94, 29.25, 29.54, 30.11, and 30.53 degrees 2θ (±0.2 degrees); Compound 1 Form X is characterized by an XRPD pattern comprising all of the following peaks 5.34, 5.88, 9.45, 10.71, 11.84, 13.36, 15.06, 16.55, 17.99, 18.80, 21.69, 22.60, 23.59, 25.54, and 26.98 degrees 2θ (±0.2 degrees) degrees 2θ (±0.2 degrees); and Compound 1 Form Y is characterized by an XRPD pattern comprising all of the following peaks 9.77, 10.22, 11.09, 11.60, 12.83, 13.20, 13.71, 14.57, 14.99, 16.06, 16.55, 17.43, 18.12, 18.45, 18.98, 19.17, 19.62, 19.85, 20.56, 20.78, 20.89, 21.13, 21.41, 21.59, 22.02, 22.28, 22.72, 22.93, 23.47, 24.06, 24.22, 24.54, 24.73, 25.34, 25.68, 26.01, 26.41, 27.04, 27.47, 27.78, 28.12, 28.32, 28.77, 29.41, 30.31, 31.01, 31.24, 31.54, and 32.18 degrees 2θ (±0.2 degrees). ### Claim 7 (depends on 3) The crystalline solid of claim 3, wherein Compound 1 Form R is characterized by an endotherm with a first onset temperature of about 110° C. and a second onset temperature of about 226° C. in a DSC thermogram, or is characterized by a weight loss of about 27.5 wt % between the temperatures of 46-177° C. in a TGA thermogram; and Compound 1 Form U is characterized by an endotherm with an onset temperature of about 199° C. in a DSC thermogram. ### Claim at position 8 8-43. (canceled) ### Claim 44 A crystalline salt of Compound 1 having the structure wherein the crystalline salt of Compound 1 is selected from Compound 1 Hemi-edisylate Form A, Compound 1 Heminapadisylate Form A, Compound 1 Napsylate Form A, Compound 1 Napsylate Form B, Compound 1 Napsylate Form C, and mixtures thereof. ### Claim 45 (canceled) ### Claim 46 (depends on 44) The crystalline salt of claim 44, wherein Compound 1 Hemi-edisylate Form A is characterized by an XRPD pattern comprising one or more peaks selected from 4.99, 5.99, 10.05, 10.37, 12.11, 13.49, 15.30, 16.20, 17.62, 18.64, 20.09, 21.00, 22.30, 23.44, 24.53, 25.23, 27.28, 27.96, and 28.70 degrees 2θ (±0.2 degrees); Compound 1 Heminapadisylate Form A is characterized by an XRPD pattern comprising one or more peaks selected from 4.74, 8.03, 10.50, 12.27, 12.72, 14.37, 15.38, 15.92, 16.33, 16.96, 18.16, 18.72, 19.13, 20.01, 21.11, 22.96, 23.83, 24.89, 25.68, 26.69, 27.53, and 28.24 degrees 2θ (±0.2 degrees); and Compound 1 Napsylate Form A is characterized by an XRPD pattern comprising one or more peaks selected from 4.74, 6.88, 8.12, 8.60, 9.52, 10.65, 10.91, 11.42, 12.36, 13.39, 13.80, 14.32, 15.08, 16.32, 16.85, 17.29, 17.68, 18.40, 18.54, 19.26, 19.51, 19.72, 20.01, 20.31, 20.55, 21.25, 21.42, 21.95, 22.23, 22.91, 23.26, 24.12, 24.36, 25.13, 25.57, 26.07, 26.25, 26.99, 27.48, 27.84, 28.17, 28.95, and 30.05 degrees 2θ (±0.2 degrees). ### Claim 47 (depends on 44) The crystalline salt of claim 44, wherein Compound 1 Hemi-edisylate Form A is characterized by an XRPD pattern comprising one or more peaks selected from 4.99, 5.99, 12.11, 13.49, 18.64, 20.09, 21.00, 22.30, 24.53, and 27.28 degrees 2θ (±0.2 degrees); Compound 1 Heminapadisylate Form A is characterized by an XRPD pattern comprising one or more peaks selected from 4.74, 8.03, 10.50, 12.27, 16.33, 16.96, 18.72, 19.13, 21.11, 22.96, 23.83, 24.89, and 25.68 degrees 2θ (±0.2 degrees); and Compound 1 Napsylate Form A is characterized by an XRPD pattern comprising one or more peaks selected from 4.74, 8.12, 8.60, 13.39, 13.80, 15.08, 16.32, 16.85, 18.40, 21.25, 21.42, 22.91, 24.12, 24.36, 26.99, and 28.95 degrees 2θ (±0.2 degrees). ### Claim 48 (depends on 44) The crystalline salt of claim 44, wherein Compound 1 Hemi-edisylate Form A is characterized by an XRPD pattern comprising all of the following peaks 4.99, 5.99, 12.11, 13.49, 18.64, 20.09, 21.00, 22.30, 24.53, and 27.28 degrees 2θ (±0.2 degrees); Compound 1 Heminapadisylate Form A is characterized by an XRPD pattern comprising all of the following peaks 4.74, 8.03, 10.50, 12.27, 16.33, 16.96, 18.72, 19.13, 21.11, 22.96, 23.83, 24.89, and 25.68 degrees 2θ (±0.2 degrees); and Compound 1 Napsylate Form A is characterized by an XRPD pattern comprising all of the following peaks 4.74, 8.12, 8.60, 13.39, 13.80, 15.08, 16.32, 16.85, 18.40, 21.25, 21.42, 22.91, 24.12, 24.36, 26.99, and 28.95 degrees 2θ (±0.2 degrees). ### Claim 49 (depends on 44) The crystalline salt of claim 44, wherein Compound 1 Hemi-edisylate Form A is characterized by an XRPD pattern comprising all of the following peaks 4.99, 5.99, 10.05, 10.37, 12.11, 13.49, 15.30, 16.20, 17.62, 18.64, 20.09, 21.00, 22.30, 23.44, 24.53, 25.23, 27.28, 27.96, and 28.70 degrees 2θ (±0.2 degrees); Compound 1 Heminapadisylate Form A is characterized by an XRPD pattern comprising all of the following peaks 4.74, 8.03, 10.50, 12.27, 12.72, 14.37, 15.38, 15.92, 16.33, 16.96, 18.16, 18.72, 19.13, 20.01, 21.11, 22.96, 23.83, 24.89, 25.68, 26.69, 27.53, and 28.24 degrees 2θ (±0.2 degrees); and Compound 1 Napsylate Form A is characterized by an XRPD pattern comprising all of the following peaks 4.74, 6.88, 8.12, 8.60, 9.52, 10.65, 10.91, 11.42, 12.36, 13.39, 13.80, 14.32, 15.08, 16.32, 16.85, 17.29, 17.68, 18.40, 18.54, 19.26, 19.51, 19.72, 20.01, 20.31, 20.55, 21.25, 21.42, 21.95, 22.23, 22.91, 23.26, 24.12, 24.36, 25.13, 25.57, 26.07, 26.25, 26.99, 27.48, 27.84, 28.17, 28.95, and 30.05 degrees 2θ (±0.2 degrees). ### Claim 50 (depends on 46) The crystalline salt of claim 46, wherein Compound 1 Hemi-edisylate Form A is characterized by an endotherm with an onset temperature of about 259° C. in a DSC thermogram, Compound 1 Heminapadisylate Form A is characterized by an endotherm with an onset temperature of about 205° C. in a DSC thermogram; and Compound 1 Napsylate Form A is characterized by an endotherm of about 63° C. in a DSC thermogram. ### Claim 51 (depends on 46) The crystalline salt of claim 46, wherein Compound 1 Hemi-edisylate Form A is characterized by a weight loss about 0.6 wt % up to a temperatures of 135° C. in a TGA thermogram, Compound 1 Heminapadisylate Form A is characterized by a weight loss about 1.5 wt % up to a temperatures of 144° C. in a TGA thermogram; and Compound 1 Napsylate Form A is characterized by a weight loss about 5.2 wt % up to a temperatures of 165° C. in a TGA thermogram. ### Claim at position 17 52-65. (canceled) ### Claim 66 A crystalline fumaric acid salt of Compound 1 wherein the crystalline fumaric acid salt of Compound 1 is selected from Compound 1 Hemifumarate Form C, Compound 1 Hemifumarate Form D, Compound 1 Hemifumarate Form E, Compound 1 Hemifumarate Form F, and mixtures thereof. ### Claim 67 (canceled) ### Claim 68 (depends on 66) Compound 1 Hemifumarate Form E according to claim 66, characterized by an XRPD pattern comprising one or more peaks selected from 5.17, 5.46, 7.07, 9.64, 10.37, 10.95, 11.44, 12.38, 13.86, 14.17, 14.71, 15.41, 15.57, 16.20, 16.47, 17.89, 18.09, 18.87, 19.54, 20.51, 21.34, 21.65, 22.18, 22.72, 23.17, 23.41, 23.81, 24.42, 25.23, 25.64, 26.14, 27.18, 27.64, 28.02, 28.90, 29.26, 29.72, 30.48, 30.96, 31.72, and 32.84 degrees 2θ (±0.2 degrees). ### Claim 69 (depends on 66) Compound 1 Hemifumarate Form E according to claim 66, characterized by an XRPD pattern comprising one or more peaks selected from 7.07, 9.64, 11.44, 15.41, 16.20, 16.47, 19.54, 20.51, 22.18, 22.72, 23.81, 26.14, and 27.18 degrees 2θ (±0.2 degrees). ### Claim 70 (depends on 66) Compound 1 Hemifumarate Form E according to claim 66, characterized by an XRPD pattern comprising all of the following peaks 7.07, 9.64, 11.44, 15.41, 16.20, 16.47, 19.54, 20.51, 22.18, 22.72, 23.81, 26.14, and 27.18 degrees 2θ (±0.2 degrees). ### Claim 71 (depends on 66) Compound 1 Hemifumarate Form E according to claim 66, characterized by XRPD pattern comprising all of the following peaks 5.17, 5.46, 7.07, 9.64, 10.37, 10.95, 11.44, 12.38, 13.86, 14.17, 14.71, 15.41, 15.57, 16.20, 16.47, 17.89, 18.09, 18.87, 19.54, 20.51, 21.34, 21.65, 22.18, 22.72, 23.17, 23.41, 23.81, 24.42, 25.23, 25.64, 26.14, 27.18, 27.64, 28.02, 28.90, 29.26, 29.72, 30.48, 30.96, 31.72, and 32.84 degrees 2θ (±0.2 degrees). ### Claim 72 (depends on 68) Compound 1 Hemifumarate Form E according to claim 68, characterized by a solid state 13C NMR spectrum with peaks at 171.3, 170.6, 167.1, 167.0, 165.5, 164.2, 164.0, 160.9, 160.0, 157.8, 149.9, 147.0, 138.2, 136.1, 129.5, 128.1, 125.3, 123.5, 121.2, 120.3, 120.0, 114.9, 114.0, 102.3, 64.2, 62.7, 61.4, 56.0, 55.5, 26.6, and 21.6±0.2 ppm, relative to the 170.6 ppm Chemical Shift. ### Claim 73 (depends on 68) Compound 1 Hemifumarate Form E according to claim 68, characterized by a solid state 19F NMR spectrum with peaks at 85.7, 84.8, 79.1, 44.9, 41.8, 5.0, 2.0, 1.3, −35.0, −38.0, −38.7, −43.0, −70.7, −72.6, −74.8, −77.6, −77.9, −78.5, −82.9, −114.8, −115.9, −117.8, −118.5, −122.9, −154.6, −155.8, −157.7, −158.4, −162.8, −194.5, −195.8, −197.6, −198.3, and −202.7±0.2 ppm, relative to the −118.5 ppm Chemical Shift from the Cross Polarization Experiment. ### Claim 74 (depends on 68) Compound 1 Hemifumarate Form E according to claim 68, characterized by a solid state 19F NMR spectrum with peaks at 45.1, 5.0, 2.1, −34.9, −38.1, −38.7, −74.3, −74.8, −77.7, −114.7, −115.9, −117.9, −118.8, −122.8, −154.6, −155.9, −157.8, −158.4, −162.8, −194.5, −197.7, and −198.5±0.2 ppm, relative to the −118.8 ppm Chemical Shift from the HPDEC Experiment. ### Claim 75 (depends on 66) A pharmaceutical composition comprising Compound 1 Hemifumarate Form E of claim 66 and a pharmaceutically acceptable excipient. ### Claim 76 (depends on 66) A method of treating cancer, comprising administering to a subject in need thereof. Compound 1 Hemifumarate Form E of claim 66. ### Claim at position 29 77-81. (canceled)