Process for preparing {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate having high purity

A process for preparing {6-[(diethylamino) methyl]naphthalen-2-yl}methyl[4-(hydroxycarbamoyl) phenyl]carbamate and/or a pharmaceutically acceptable salt thereof, said process comprising the steps of:

• STEP 1
• reacting a halogenating agent with a compound of formula (I)
• in an aprotic dipolar solvent insensitive to acidity to produce a compound of formula (II)
• wherein X is halogen,
• STEP 2
• i) preparing a solution or a suspension of the compound of formula (II) in an organic solvent, wherein the organic solvent has a water content lower than 0.5% w/w;
• and
• ii) adding a 50% w/w hydroxylamine water solution to the solution or suspension obtained from step i),
• wherein the {6-[(diethylamino) methyl]naphthalen-2-yl}methyl[4-(hydroxycarbamoyl) phenyl]carbamate and/or a pharmaceutically acceptable salt thereof has 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 HPLC 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:
• Time
• Eluent A
• Eluent B
• (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.