Methanesulfonyl chloride → Dronedarone Hydrochloride

Participants

Reaction Conditions

Reaction Steps

Under a temperature range from room temperature to reflux temperature, preferably reflux temperature, 5-amino-2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)benzofuran is reacted with methanesulfonyl chloride in a mixture of acetone and acetonitrile solvent to provide a crude dronedarone hydrochloride, wherein an ratio of acetone and acetonitrile used is in the range of 0˜5:1 (v/v), preferably 0.2˜3:1 (v/v), more preferably 0.5˜1:1 (v/v), and an amount of methanesulfonyl chloride used is in the range of is 1 to 5 equivalents, and preferably 1.5 to 4 equivalents, and more preferably 2 to 3 equivalents relative to the compound A to obtain a reaction mixture. When the reaction is terminated, the reaction mixture is cooled to −40 to 50° C., preferably −15 to 40° C., more preferably −10 to 35° C. to obtain crude dronedarone hydrochloride. Then the crude dronedarone hydrochloride can be purified to obtain highly pure dronedarone hydrochloride. If desired, the obtained dronedarone hydrochloride can be converted to highly pure dronedarone via alkaline solvent, or further converted to other pharmaceutically acceptable salts of dronedarone.

Provenance & Evidence