# US 12,759,981 B2 · Cholinate of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[([{1-[2-fluoro-4-(trifluoromethyl)-phenyl]cyclopropyl}carbonyl)amino]benzoic acid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,759,981 B2 - Document ID: US12759981B2 - Status: Granted - Kind: B2 - Application number: 18/572,042 - Filed: 2022-07-04 - Published: 2025-09-11 - Granted: 2026-10-13 - Earliest claimed: 2021-07-05 - Assignees: Bayer Aktiengesellschaft - Applicants: Bayer Aktiengesellschaft - Inventors: Stefan Bäurle; Hans-Georg Lerchen; Britta Olenik; Guillaume Levilain; Birgit Keil; Sylvia Dworacek; Antje Rottmann; Andrea Rotgeri; Robert Craig Melling - Web page: https://patentgrep.com/patent/US12759981B2 ## CPC - C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms - A61K 31/415: 1,2-Diazoles - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - 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) ## Abstract The present invention relates to the choline salt (cholinate) of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-4-(trifluoromethyl)-phenyl]cyclopropyl}carbonyl)amino]benzoic acid. In particular, the invention relates to the compound according to formula (II): or a tautomer, solvate or hydrate thereof, as well as to medical uses of the cholinate according to the invention. ## Claims ### Claim 1 A cholinate of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-4 (trifluoromethyl)phenyl]-cyclopropyl}carbonyl)amino]benzoic acid. ### Claim 2 (depends on 1) The cholinate according to claim 1, wherein the cholinate is according to formula (II): or a solvate, hydrate or tautomer thereof. ### Claim 3 (depends on 1) The cholinate according to claim 1, which is in crystalline form. ### Claim 4 (depends on 3) The crystalline cholinate according to claim 3, which is polymorphic form A. ### Claim 5 (depends on 3) The crystalline cholinate according to claim 3, characterized by the substantially same X-ray powder diffraction (XRPD) pattern as in FIG. 1. ### Claim 6 (depends on 3) The crystalline cholinate according to claim 3, characterized by a X-ray powder diffractogram measured at 25° C. and with Cu—K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Θ value±0.2°: 12.99°, 20.42°, and 20.64°. ### Claim 7 (depends on 3) The crystalline cholinate according to claim 3, characterized by a X-ray powder diffractogram measured at 25° C. and with Cu—K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Θ value±0.2°: 12.99°, 20.42°, 20.64°, 18.84°, and 22.32°. ### Claim 8 (depends on 3) The crystalline cholinate according to claim 3, characterized by a X-ray powder diffractogram measured at 25° C. and with Cu—K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Θ value: 12.99°, 20.42°, 20.64°, 18.84°, 22.32°, 15.74°, and 20.75°. ### Claim 9 (depends on 3) The crystalline cholinate according to claim 3, characterized by the substantially the same IR pattern as in FIG. 2. ### Claim 10 (depends on 3) The crystalline cholinate according to claim 3, characterized by an IR pattern displaying at least the following bands, quoted as peak maxima in cm−1: 1123, 1309, 1083. ### Claim 11 (depends on 3) The crystalline cholinate according to claim 3, characterized by an IR pattern displaying at least the following bands, quoted as peak maxima in cm−1: 1123, 1309, 1083, 1324, and 808. ### Claim 12 (depends on 3) The crystalline cholinate according to claim 3, characterized by an IR pattern displaying at least the following bands, quoted as peak maxima in cm−1: 1123, 1309, 1083, 1324, 808, 1091, and 874. ### Claim 13 (depends on 3) The crystalline cholinate according to claim 3, characterized by an IR pattern displaying at least the following bands, quoted as peak maxima in cm−1: 1123, 1309, 1083, 1324, 808, 1091, 874, 1530, 954, and 835. ### Claim 14 (depends on 1) A method of preparing the cholinate according to claim 1, said method comprising the step of adding to a compound of formula (I): a compound of formula (III): thereby forming said cholinate of formula (II): ### Claim 15 (depends on 14) The method according to claim 14, wherein the method further comprises the steps of: a) dissolving the cholinate of formula (II) in a solvent selected from the group consisting of acetonitrile, ethanol, methyl tert-butyl ether, ethyl acetate, heptane, toluene, tetrahydrofuran, butanol, acetone, water and mixtures thereof, to form a solution; b) cooling the solution to precipitate the crystalline cholinate; and, c) filtering the resulting crystalline cholinate from the solution. ### Claim 16 (depends on 1) A pharmaceutical composition comprising a cholinate according to claim 1, and a pharmaceutically acceptable diluent or carrier. ### Claim 17 (depends on 1) A method of treating a disease selected from the group consisting of diabetic neuropathic pain, interstitial cystitis/bladder-pain-syndrome, endometriosis, and endometriosis-associated pain, comprising the step of administering the cholinate of claim 1 in a pharmaceutical dosage form to a patient in need thereof. ### Claim 18 (depends on 17) The method of claim 17, wherein said pharmaceutical dosage form comprises the cholinate and a pharmaceutically acceptable diluent or a carrier.