Methanesulfonyl chloride → Dronedarone Hydrochloride

HRID 449173Notes

Reaction equation

HRID 449173 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH2:10][CH2:11][CH2:12][CH3:13])=[C:7]([C:14](=[O:34])[C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][N:25]([CH2:30][CH2:31][CH2:32][CH3:33])[CH2:26][CH2:27][CH2:28][CH3:29])=[CH:17][CH:16]=3)[C:6]=2[CH:35]=1.[CH3:36][S:37]([Cl:40])(=[O:39])=[O:38]>O1CCCC1>[CH3:13][CH2:12][CH2:11][CH2:10][C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([NH:1][S:37]([CH3:36])(=[O:39])=[O:38])=[CH:35][C:6]=2[C:7]=1[C:14]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][N:25]([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:17][CH:16]=1)=[O:34].[ClH:40]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chloride2×HCID 11488441(5-Amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone

Product 1

HCID 219025Dronedarone Hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
12.5 °C

Procedure

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 tetrahydrofuran solvent to provide a crude dronedarone hydrochloride, wherein an amount of tetrahydrofuran used is in the range of 0 to 15 parts by volume, preferably 3 to 12 parts by volume, more preferably 5 to 10 parts by volume based on 1 part by weight of the compound A, and an amount of methanesulfonyl chloride used is in the range of is 1 to 8 equivalents, and preferably 1.5 to 5 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 −25 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.

Workup

  1. customto obtain a reaction mixture
  2. customWhen the reaction is terminated
  3. customto obtain crude dronedarone hydrochloride
  4. customThen the crude dronedarone hydrochloride can be purified

Sources & evidence

ORD record
ord-74a9d23c9c9d492c9881023300050010
Source dataset
uspto-grants-2013_07
Patent number
US08481763B2

Reaction notes

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