8-Hydroxyquinoline → tert-Butyl-7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

HRID 1020681ノート

反応式

HRID 1020681 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][C:14](Br)=[CH:15][CH:16]=3)[N:11]([CH3:22])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][NH:33][C:32](=[O:36])[CH:31]=2)=[C:26]([O:37][CH3:38])[CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CS(C)=O.[Cu](I)I>[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][C:14]([N:33]4[CH:34]=[CH:35][C:30]([C:27]5[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][C:26]=5[O:37][CH3:38])=[CH:31][C:32]4=[O:36])=[CH:15][CH:16]=3)[N:11]([CH3:22])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 532180124-(4-Chloro-2-methoxyphenyl)pyridin-2(1H)-oneHCID 57950468tert-butyl 7-bromo-9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate

生成物 1

HCID 57950380tert-Butyl-7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate収率 54.6%

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
130 °C

実験手順

tert-Butyl-7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (0.19 g, 0.81 mmol), 4-(4-chloro-2-methoxyphenyl)pyridin-2(1H)-one (0.30 g, 0.81 mmol), Cs2CO3 (0.29 g, 0.89 mmol) were diluted with DMSO (3.3 mL), and argon was bubbled through the suspension for 10 min. 8-Hydroxyquinoline (59 mg, 0.41 mmol) and copper iodide (0.18 g, 0.97 mmol) were added, and the resulting suspension was placed under vacuum for 15 min. The system was flushed with argon, and the degassing/argon flushing process was repeated a total of three times. The reaction mixture was heated at 130° C. for 18 h and stirred under argon. The suspension was cooled. A solution of 20% NH4OH in MeOH (40 mL) was added, and the resulting mixture was stirred for 1 h. The mixture was diluted with CH2Cl2 and filtered through celite. The filtrate was washed with brine (2×50 mL), dried over Na2SO4, and concentrated under reduced pressure. Flash chromatography (40 g ISCO (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 3 column volumnes then increase to 50:50 over 10 column volumnes and hold for 10 column volumes) gave the title compound (0.23 g, 54%) as an olive-green film: 1H NMR (500 MHz, DMSO-d6) δ 7.65 (d, J=7.0 Hz, 1H), 7.54 (d, J=2.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 7.25 (d, J=1.5 Hz, 1H), 7.13 (dd, J=8.0, 1.5 Hz, 1H), 7.02 (dd, J=8.0, 1.5 Hz, 1H), 6.55 (d, J=2.0 Hz, 1H), 6.54 (dd, J=7.0, 1.5 Hz, 1H), 4.64 (s, 2H), 3.87 (s, 3H), 3.68-3.66 (m, 5H), 2.74-2.72 (m, 2H), 1.46 (s, 9H).

後処理

  1. customwas bubbled through the suspension for 10 min
  2. customThe system was flushed with argon
  3. temperatureThe suspension was cooled
  4. additionA solution of 20% NH4OH in MeOH (40 mL) was added
  5. stirringthe resulting mixture was stirred for 1 h
  6. additionThe mixture was diluted with CH2Cl2
  7. filtrationfiltered through celite
  8. washThe filtrate was washed with brine (2×50 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. temperatureFlash chromatography (40 g ISCO (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 3 column volumnes then increase to 50:50 over 10 column volumnes

出典と根拠

ORDレコード
ord-8c47285438c94258a83cc8bdfe463925
出典データセット
uspto-grants-2014_05
特許番号
US08716308B2

反応ノート

読み込み中…