# US 2019/0169227 A1 · Method for production of novel galeterone analogs and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169227 A1 - Document ID: US20190169227A1 - Status: Published application - Kind: A1 - Application number: 16/310,000 - Filed: 2017-06-22 - Published: 2019-06-06 - Earliest claimed: 2016-06-22 - Assignees: University of Maryland, Baltimore - Inventors: Vincent C.O. Njar; Puranik Purushottamachar; Francis Murigi - Web page: https://patentgrep.com/patent/US20190169227A1 ## CPC - C07J 43/003: {not condensed} - A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) - A61P 35/00: Antineoplastic agents - C07J: STEROIDS (seco-steroids C07C) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Galeterone and its C-3 analogs are of substantial interest because of their multi-target anticancer activities, including AR and Mnk degrading activities. Provided are novel procedures for gram-scale, high-yield synthesis of C-3 analogs of galeterone, including 3β-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (galeterone 3β-imidazole) and 3β-(pyridine-4-ylmethoxy)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (galeterone 3β-pyridine methoxylate). ## Claims ### Claim 1 A process for preparing 3-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (2, 5), the process comprising: a first reaction comprising reacting a compound having Formula 1 (1) to produce 3-azido-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (7, 8); and a second reaction comprising reacting the 3-azido-17-(1H-benzimidazole-1-ypandrosta-5,16-diene (7, 8) to produce 3-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (2, 5). ### Claim 2 (depends on 1) The process according to claim 1, wherein the first reaction comprises mesylation of the compound having Formula 1 (1) to produce a mesylate (4), and azidation of the mesylate (4) to produce the 3-azido-17-(1H-benziandazole-1-ybandrosta-5,16-diene (7, 8). ### Claim 3 (depends on 1) The process according to claim 1, wherein the second reaction comprises reduction of the 3-azido-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (7, 8) to produce an amine (9, 10), and cyclization of the amine (9, 10) to produce the 3-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (2, 5). ### Claim 4 (depends on 2) The process according to claim 2, wherein the azidation comprises contacting the mesylate (4) with an alkali metal azide or an organic azide, so as to perform the azidation in a stereo-selective manner to produce 3α-azido-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (7) or 3β-azido-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (8). ### Claim 5 (depends on 4) The process according to claim 4, wherein the azidation comprises contacting the mesylate (4) with trimethylsilyl azide in the presence of a suitable Lewis acid and a suitable solvent to produce the 3β-azido-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (8). ### Claim 6 (depends on 5) The process according to claim 5, wherein 15 equivalents of the trimethylsilyl azide and 27 equivalents of the suitable Lewis acid are added for 1 equivalent of the mesylate (4). ### Claim 7 (depends on 4) The process according to claim 4, wherein the azidation comprises contacting the mesylate (4) with sodium azide in the presence of a suitable catalyst and a suitable solvent to produce the 3α-azido-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (7). ### Claim 8 (depends on 3) The process according to claim 3, wherein the reduction and the cyclization are performed in a stereo-retentive manner. ### Claim 9 A process for preparing galeterone 3β-pyridine methoxylate (3), the process comprising contacting a compound having Formula 1 (1) with 4-(bromomethyl)pyridine hydrobromide in the presence of a suitable base, a suitable salt, and at least one suitable solvent to produce the galeterone 3β-pyridine methoxylate (3). ### Claim 10 (depends on 9) The process according to claim 9, wherein the solvent is a mixture of tetrahydrofuran (THF) and dimethylformamide (DMF), and a ratio of THF to DMF (THF:DMF) is less than 1:2. ### Claim 11 (depends on 10) The process according to claim 10, wherein the ratio of THF to DMF is 1:16. ### Claim 12 (depends on 9) The process according to claim 9, wherein the salt is one of lithium carbonate and cesium carbonate. ### Claim 13 (depends on 9) The process according to claim 9, wherein the salt is lithium carbonate. ### Claim 14 (depends on 9) The process according to claim 9, wherein the base is triethyl amine ### Claim 15 (depends on 9) The process according to claim 9, comprising: adding the compound having Formula 1 to a first solvent, treating the compound having Formula 1 in the first solvent with sodium hydride, adding the treated compound having Formula 1 in the first solvent to a second solvent, adding the suitable salt, and then adding the 4-(bromomethyl)pyridine hydrobromide, so as to produce the galeterone 3β-pyridine methoxylate (3). ### Claim 16 A process for preparing an androgen receptor degrading agent or a MAPK-interacting kinase degrading agent, the process comprising preparing a compound having Formula 2 (7) or a compound having Formula 3 (8): ### Claim 17 (depends on 16) The process according to claim 16, wherein the preparing of the compound having Formula 2 (7) or the compound having Formula 3 (8) comprises: mesylation of a compound having Formula 1 (1) to produce a mesylate (4); and azidation of the mesylate (4). ### Claim 18 (depends on 17) The process according to claim 17, wherein the azidation comprises contacting the mesylate (4) with an alkali metal azide or an organic azide, so as to perform the azidation in a stereo-selective manner to produce the compound having Formula 2 (7) or the compound having Formula 3 (8). ### Claim 19 (depends on 17) The process according to claim 17, wherein the azidation comprises contacting the mesylate (4) with trimethylsilyl azide in the presence of a suitable Lewis acid and a suitable solvent to produce the compound having Formula 3 (8). ### Claim 20 (depends on 19) The process according to claim 19, wherein 15 equivalents of the trimethylsilyl azide and 27 equivalents of the suitable Lewis acid are added for 1 equivalent of the mesylate (4).