Claims for Patent: 12,606,519

Summary for Patent: 12,606,519

Title:	Process for preparing {6-[(diethylamino) methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl] carbamate having high purity
Abstract:	A process for obtaining {{6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate and/or pharmaceutically acceptable salts thereof having high purity is described. This process allows to obtain a product having an amount of any single unknown impurity equal to or less than 0.10%, as well as a product having a purity greater than 99.5%, preferably equal to or greater than 99.6%.An HPLC method for determining the purity of the product and possible impurities thereof is also described.
Inventor(s):	Stefano Turchetta, Maurizio Zenoni, Elio Ullucci, Stefania Cocciolo, Giorgio BERARDI, Nakia Maulucci
Assignee:	Italfarmaco SpA
Application Number:	US18/338,435
Patent Claims:	1. {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate, having an amount of any single unidentified impurity equal to or lower than 0.10 area % as determined by HPLC, wherein the unidentified impurity is selected from the group consisting of an unidentified impurity at a Relative Retention Time (RRT) of 0.93±0.02, an unidentified impurity at an RRT of 1.21±0.02, an unidentified impurity at an RRT of 1.51±0.02, and an unidentified impurity at an RRT of 1.75±0.02, wherein the RRT is determined using an HPLC method under the following operating conditions: Stationary phase: support based on silica particles containing C18 alkyl chains and having a carbon load lower than 9% by weight; Mobile phase A: Water buffered at pH 3.7-3.8 Mobile phase B: Methanol buffered at pH 3.7-3.8 using the following gradient elution method: Eluent A Eluent B Time % % (min) (v/v) (v/v) 0 75 25 5 75 25 35 10 90 40 10 90 40.1 75 25 50 (end run) 75 25 and subsequent detection of the {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate by means of a detector; or having an amount of any single impurity other than intermediate (I) or amide (la) equal to or lower than 0.15%. 2. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, having an amount of a single impurity other than intermediate (I) or amide (la) equal to or lower than 0.10%. 3. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, having a purity equal to or greater than 99.6%. 4. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, wherein the detector employed in the HPLC method is a detector of UV, MS or RID type. 5. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 4, wherein the detector employed in the HPLC method is a 263 nm UV detector. 6. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, wherein the buffer employed in the HPLC method is formate-formic acid buffer at pH 3.7-3.8. 7. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, wherein the temperature employed in the HPLC method is 25±1° C. 8. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, wherein the injection volume employed in the HPLC method is 5 μL. 9. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, wherein the flow rate employed in the HPLC method is 0.25 mL/min. 10. The {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate hydrochloride monohydrate according to claim 1, wherein DMSO is employed as a diluent for {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate or a pharmaceutically acceptable salt in the HPLC method.