# US 6,723,734 B2 · Salt of naphthyridine carboxylic acid derivative > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,723,734 B2 - Document ID: US6723734B2 - Status: Granted - Kind: B2 - Application number: 10/223,850 - Filed: 2002-08-20 - Published: 2003-03-13 - Granted: 2004-04-20 - Earliest claimed: 1997-03-21 - Assignees: LG Life Sciences Ltd. - Inventors: Ae Ri Kim; Jin Hwa Lee; Ki Sook Park; Jong Ryoo Choi; Tae Hee Lee; Jay Hyok Chang; Do Hyun Nam; Hoon Choi - Web page: https://patentgrep.com/patent/US6723734B2 ## CPC - C07D 471/04: Ortho-condensed systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract 7-(3-Aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof, processes for their preparation, pharmaceutical compositions comprising them, and their use in antibacterial therapy. ## Claims ### Claim 1 A crystal form of 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate.nH2O, wherein n is in the range of from 1 to 4. ### Claim 2 (depends on 1) The compound according to claim 1 having peaks at 2θ=8.0, 12.2 and 14.7° in its X-ray diffraction pattern. ### Claim 3 (depends on 1) The compound according to claim 1 having an X-ray diffraction pattern substantially as shown in FIG. 7. ### Claim 4 (depends on 1) The compound according to claim 1 having peaks at 2θ=7.7 and 11.8° in its X-ray diffraction pattern. ### Claim 5 (depends on 1) The compound according to claim 1 having an X-ray diffraction pattern substantially as shown in FIG. 6. ### Claim 6 (depends on 1) A pharmaceutical composition comprising a compound according to claim 1, together with a pharmaceutically acceptable carrier or excipient. ### Claim 7 (depends on 1) A method of treating bacterial infections in humans and animals comprising administering a therapeutically effective amount of a compound according to claim 1. ### Claim 8 (depends on 1) A process for preparing a compound according to claim 1, comprising reacting 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid with methanesulfonic acid, crystallizing a resulting compound from a solution, and adjusting the hydration of the resulting compound. ### Claim 9 (depends on 1) A process for preparing a compound according to claim 1, comprising exposing 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate anhydrate, or a solvate thereof, to a relative humidity of at least 75%. ### Claim 10 (depends on 9) The process according to claim 9, wherein the solvate comprises at least one organic solvent which is C1-C4 haloalkane or C1-C8 alcohol. ### Claim 11 A solvate comprising a crystal form of 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and at least one organic solvent. ### Claim 12 (depends on 6) The pharmaceutical composition according to claim 6, wherein n is 1.5. ### Claim 13 (depends on 6) The pharmaceutical composition according to claim 6, wherein the compound has peaks at 2θ=8.0, 12.2 and 14.7° in its X-ray diffraction pattern. ### Claim 14 (depends on 6) The pharmaceutical composition according to claim 6, wherein the compound has an X-ray diffraction pattern substantially as shown in FIG. 7. ### Claim 15 (depends on 6) The pharmaceutical composition according to claim 6, wherein n is 3. ### Claim 16 (depends on 6) The pharmaceutical composition according to claim 6, wherein the compound has peaks at 2θ=7.7 and 11.8° in its X-ray diffraction pattern. ### Claim 17 (depends on 6) The pharmaceutical composition according to claim 6, wherein the compound has an X-ray diffraction pattern substantially as shown in FIG. 6. ### Claim 18 (depends on 6) The pharmaceutical composition according to claim 6, wherein the compound has a moisture content of from 4 to 6%. ### Claim 19 (depends on 6) The pharmaceutical composition according to claim 6, wherein the compound has a moisture content of from 9 to 11%. ### Claim 20 (depends on 8) The process according to claim 8, wherein the resulting compound is 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate.nH2O, wherein n is 1.5. ### Claim 21 (depends on 8) The process according to claim 8, wherein the resulting compound has peaks at 2θ=8.0, 12.2 and 14.7° in its X-ray diffraction pattern. ### Claim 22 (depends on 8) The process according to claim 8, wherein the resulting compound has an X-ray diffraction pattern substantially as shown in FIG. 7. ### Claim 23 (depends on 8) The process according to claim 8, wherein the solution comprises at least one of C1-C4 haloalkane, C1-C8 alcohol, and water. ### Claim 24 (depends on 23) The process according to claim 23, wherein the solution comprises at least one of dichloromethane, chloroform, 1,2-dichloroethane, methanol, ethanol, propanol, and water. ### Claim 25 (depends on 9) The process according to claim 9, wherein the compound prepared is 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate.nH2O, wherein n is 1.5. ### Claim 26 (depends on 9) The process according to claim 9, wherein the compound prepared is 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate.nH2O, wherein n is 3. ### Claim 27 (depends on 9) The process according to claim 9, wherein the compound prepared has peaks at 2θ=7.7 and 11.8° in its X-ray diffraction pattern. ### Claim 28 (depends on 9) The process according to claim 9, wherein the compound prepared has an X-ray diffraction pattern substantially as shown in FIG. 6. ### Claim 29 (depends on 10) The process according to claim 10, wherein the at least one organic solvent is ethanol, dichloromethane, isopropanol, or 2-methyl-2-propanol. ### Claim 30 (depends on 11) The solvate according to claim 11, wherein the at least one organic solvent is C1-C4 haloalkane or C1-C8 alcohol. ### Claim 31 (depends on 11) The solvate according to claim 11, wherein the at least one organic solvent is ethanol, dichloromethane, isopropanol, or 2-methyl-2-propanol. ### Claim 32 A process for preparing a solvate of 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate with at least one organic solvent, comprising: dissolving 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate anhydrate in a mixture of ethanol and water to form a solution; heating the solution to 50° C.; cooling the solution to −3° C.; allowing the solution to stand at −3° C., wherein a solid solvate forms; filtering the solid solvate; and washing the solid solvate with a mixture of ethanol and water. ### Claim 33 (depends on 1) A method for manufacturing a pharmaceutical composition comprising mixing a compound according to claim 1, and a pharmaceutically acceptable carrier or excipient.