Methanesulfonyl chloride → Dronedarone Hydrochloride

HRID 449174ノート

反応式

HRID 449174 の反応式
[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]

参加物

5

反応物 2

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

生成物 1

HCID 219025Dronedarone Hydrochloride

試薬・触媒・溶媒 2

HCID 180Acetone溶媒2 回HCID 6342Acetonitrile溶媒2 回

反応条件

温度
12.5 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-eaf3a7f3583448dc9d6a86c68419374a
出典データセット
uspto-grants-2013_07
特許番号
US08481763B2

反応ノート

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