Methanesulfonyl chloride → Dronedarone Hydrochloride

HRID 449172

Reaktionsgleichung

Reaktionsgleichung von HRID 449172
[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]>ClCCl>[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]

Komponenten

4

Edukt 2

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

Produkt 1

HCID 219025Dronedarone Hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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 dichloromethane solvent to provide a crude dronedarone hydrochloride, wherein an amount of dichloromethane used is in the range of 0 to 30 parts by volume, preferably 10 to 25 parts by volume, more preferably 15 to 20 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 1 to 15 equivalents, and preferably 5 to 10 equivalents, and more preferably 6 to 9 equivalents relative to the compound A to obtain a reaction mixture. When the reaction is terminated, the reaction mixture is treated with alkaline reagent such as alkali metal hydroxides (such as sodium hydroxide), alkali metal carbonate or alkali metal bicarbonate such as sodium bicarbonate, preferably sodium bicarbonate. Then the obtained dronedarone is salified in the presence of hydrochloric acid in acetone solvent. Subsequently, the crude dronedarone hydrochloride is quickly crystallized. If desired, the crude dronedarone hydrochloride is purified to obtain highly pure dronedarone hydrochloride. Then the obtained dronedarone hydrochloride can be converted to highly pure dronedarone via alkaline solvent, or if desired, further converted to other pharmaceutically acceptable salts of dronedarone.

Aufarbeitung

  1. customto obtain a reaction mixture
  2. customWhen the reaction is terminated
  3. additionthe reaction mixture is treated with alkaline reagent such as alkali metal hydroxides (such as sodium hydroxide), alkali metal carbonate or alkali metal bicarbonate such as sodium bicarbonate, preferably sodium bicarbonate
  4. customSubsequently, the crude dronedarone hydrochloride is quickly crystallized
  5. customthe crude dronedarone hydrochloride is purified

Quellen und Nachweise

ORD-Eintrag
ord-f621a42165a44c4581addd8250066069
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481763B2

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