8-Hydroxyquinoline → tert-Butyl 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-10-methyl-7,8,9,10-tetrahydropyrido[3',2':4,5]pyrrolo[3,2-c]azepine-6(5H)-carboxylate

HRID 474989ノート

反応式

HRID 474989 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH2:10][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12][CH2:13][CH2:14][C:8]=3[N:7]([CH3:22])[C:6]=2[N:23]=1.[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][NH:35][C:34](=[O:38])[CH:33]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CS(C)=O.[Cu](I)I>[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][N:35]([C:2]2[CH:3]=[CH:4][C:5]3[C:9]4[CH2:10][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12][CH2:13][CH2:14][C:8]=4[N:7]([CH3:22])[C:6]=3[N:23]=2)[C:34](=[O:38])[CH:33]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

参加物

7

反応物 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 86649551tert-butyl 2-bromo-10-methyl-7,8,9,10-tetrahydropyrido[3',2':4,5]pyrrolo[3,2-c]azepine-6(5H)-carboxylate

生成物 1

HCID 66869329tert-Butyl 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-10-methyl-7,8,9,10-tetrahydropyrido[3',2':4,5]pyrrolo[3,2-c]azepine-6(5H)-carboxylate収率 70.4%

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

A suspension of tert-butyl 2-bromo-10-methyl-7,8,9,10-tetrahydropyrido[3′,2′:4,5]pyrrolo[3,2-c]azepine-6(5H)-carboxylate (0.15 g, 0.40 mmol), 4-benzyloxypyridinone (80 mg, 0.40 mmol), and Cs2CO3 (0.14 g, 0.44 mmol) in DMSO (2.3 mL) was placed under vacuum for 15 min. The system was flushed with Ar, and 8-hydroxyquinoline (17 mg, 0.12 mmol) and copper iodide (91 mg, 0.48 mmol) were added to the suspension. The evacuation/Ar flushing process was repeated twice more, and the reaction mixture was heated at 130° C. for 18 h under N2. The mixture was cooled, diluted with 5.0:3.5:1.5 NH4Cl (aq.)/NH4OH/H2O (30 mL), and the resulting suspension was stirred at ambient temperature for 30 min. The resulting solids were collected by filtration, dissolved in CH2Cl2 (40 mL) and washed with 5.0:3.5:1.5 NH4Cl (aq.)/NH4OH/H2O (2×30 mL). The resulting organic solution was dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 50:50 over 20 column volumes and held for 4 column volumes; increased to 0:100 over 10 column volumes) gave the title compound (141 mg, 70%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.98-7.95 (m, 1H), 7.81-7.79 (m, 1H), 7.49-7.37 (m, 5H), 7.30-7.27 (m, 1H), 6.15 (dd, J=7.8, 2.7 Hz, 1H), 5.98 (d, J=2.7 Hz, 1H), 5.16 (s, 2H), 4.58 (br s, 2H), 3.71 (s, 3H), 3.66 (t, J=5.4 Hz, 2H), 3.03-3.01 (m, 2H), 1.98-1.93 (m, 2H), 1.35-1.27 (m, 9H); ESI MS m/z 501 [M+H]+.

後処理

  1. additionwere added to the suspension
  2. customThe evacuation/Ar flushing process
  3. temperatureThe mixture was cooled
  4. additiondiluted with 5.0:3.5:1.5 NH4Cl (aq.)/NH4OH/H2O (30 mL)
  5. filtrationThe resulting solids were collected by filtration
  6. dissolutiondissolved in CH2Cl2 (40 mL)
  7. washwashed with 5.0:3.5:1.5 NH4Cl (aq.)/NH4OH/H2O (2×30 mL)
  8. dry with materialThe resulting organic solution was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure
  11. temperatureFlash chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 50:50 over 20 column volumes and held for 4 column volumes; increased to 0:100 over 10 column volumes)

出典と根拠

ORDレコード
ord-dc447051524741b18430cccc6e6680b1
出典データセット
uspto-grants-2014_01
特許番号
US08637501B2

反応ノート

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