Dimethyl Sulfoxide → Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzyl ester

HRID 41900

反応式

HRID 41900 の反応式
[CH3:1][N:2]([CH3:14])[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[NH:8][CH2:7][CH2:6]2.[Br:15][C:16]1[CH:26]=[CH:25][CH:24]=[C:23](Br)[C:17]=1[CH2:18][O:19][C:20](=[O:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+].CS(C)=O>ClCCl>[Br:15][C:16]1[CH:26]=[CH:25][CH:24]=[C:23]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([N:2]([CH3:14])[CH3:1])[CH:4]=3)[C:9]2=[O:13])[C:17]=1[CH2:18][O:19][C:20](=[O:22])[CH3:21]

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 574241216-(Dimethylamino)-3,4-dihydroisoquinolin-1(2H)-oneHCID 592164132,6-Dibromobenzyl acetate

生成物 1

HCID 59216405Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzyl ester収率 27.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
150 °C

実験手順

6-Dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (150 mg, 0.789 mmol), Acetic acid 2,6-dibromo-benzyl ester (487 mg, 1.58 mmol), cuprous iodide (30 mg, 0.16 mmol) and potassium carbonate (109 mg, 0.789 mmol) were deposited in a sealed vessel. 3 mL DMSO was added. Argon was bubbled through the mixture for 2 minutes and the lid was tightly closed. This was heated at 150° C. for 24 hours. Cuprous iodide (30 mg, 0.16 mmol) was added and the mixture was heated at 150° C. for an additional 24 hours. This was diluted with dichoromethane and filtered through a pad of celite. The filtrate was partitioned between dichloromethane and 5% aq. ammonium hydroxide. The dichloromethane layer was dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes) to yield Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzyl ester (93 mg, 0.22 mmol). MS (ESI) 417.1 (M+H)+.

後処理

  1. customArgon was bubbled through the mixture for 2 minutes
  2. customthe lid was tightly closed
  3. temperaturethe mixture was heated at 150° C. for an additional 24 hours
  4. filtrationfiltered through a pad of celite
  5. customThe filtrate was partitioned between dichloromethane and 5% aq. ammonium hydroxide
  6. dry with materialThe dichloromethane layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-65514fe38a97442f91fd1f3d419883e9
出典データセット
uspto-grants-2013_09
特許番号
US08536166B2

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