An Improved Commercially Feasible Process for Flecainide Acetate

Abstract

Commercially viable manufacturing process for Flecainide Acetate (I) conforming to regulatory specification and cost effective process is reported. Specifically, an improved process for the preparation of Flecainide Acetate allows isolation of anhydrous hydrochloride salt of Compound III, which facilitates the reduction of the pyridine ring with the only catalytic amount of platinum on carbon within 2 hours Therefore, simplifies the synthesis and isolation of Flecainide acetate on a commercial scale to a considerable extent.

Identification and Synthesis of Flecainide Acetate Impurities and Its Control to ICH Limit

“…of boric acid. Boric acid activates the carboxylic acid moiety by reducing the electron density at the carbonyl function, which makes the intermediate 1 more prone to amine nucleophilic substitution to facilitate the transformation in moderate to good yield" [1].…”

“…Varian 1HNMR spectra (400 MHz) and 13CNMR spectra (100 MHz) instrument were recorded inDMSO-d6, and mass spectra were determined on API-2000LCMS mass spectrometer, Applied Biosciences.IR spectrum was taken in potassium bromide and recorded on Shimadzu 8400S FTIR instrument. Differential scanning calorimetric (DSC) analysis was carried on Perkin Elmer DSC80000 instrument" [1].…”

“…After monitoring reaction progress by HPLC toluene was distilled off under vacuum, water (150L) was added and stirred for 2 hours at 25 to 30°C. Precipitated solid was filtered and washed with water (100mL), dried under vacuum for 4 hours to give free base" [1]. "Further Ethyl acetate in (225mL) and solid were added to a flask and added cooled 10% solution of ethyl acetate in HCl (100mL) were added to clear solution.…”

“…"Thus in the first step of the synthesis of compound-III, presence of a catalyst eliminated the need for chemical activation of 2aminomethyl pyridine and thus use of the hydroxybenzotriazole (HOBt) and N, N′dicyclohexylcarbodiimide (DCC) reagents was bypassed, since mole to mole ratio is used and lot of solid waste is generated during reaction workup. Therefore, these reagents were not suitable at commercial level" [1]. Compound -III was isolated as a hydrochloride salt with impurity profile found as per ICH limit with high purity (99.91 %) and satisfactory yield (85.8 %) (Fig.…”

“…This there by slows conduction of the electrical impulse within the heart. Other medication include in this class are encainide, propafenone and moricizine" [1].…”