Methanesulfonyl chloride → Dronedarone Hydrochloride

HRID 449174

Reaktionsgleichung

Reaktionsgleichung von HRID 449174
[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]>CC(C)=O.C(#N)C>[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

5

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 2

HCID 180AcetoneLösungsmittel2×HCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
12.5 °C

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 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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-eaf3a7f3583448dc9d6a86c68419374a
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481763B2

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