8-Hydroxyquinoline → tert-Butyl 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate

HRID 882015노트

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HRID 882015 반응식
Br[C:2]1[N:7]=[C:6]2[N:8]([CH3:22])[C:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:10]=3[C:5]2=[CH:4][CH:3]=1.[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][NH:34][C:33](=[O:37])[CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CS(C)=O.[Cu](I)I>[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][N:34]([C:2]2[N:7]=[C:6]3[N:8]([CH3:22])[C:9]4[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:10]=4[C:5]3=[CH:4][CH:3]=2)[C:33](=[O:37])[CH:32]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

참가 물질

7

반응물 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 71551310tert-Butyl 2-bromo-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate

생성물 1

HCID 67988826tert-Butyl 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate수율 52.4%

시약·촉매·용매 2

HCID 83717Copper iodide촉매HCID 679Dimethyl Sulfoxide용매

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온도
130 °C

실험 절차

tert-Butyl 2-bromo-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (0.73 g, 2.0 mmol), 4-benzyloxy pyridinone (0.44 g, 2.2 mmol), and Cs2CO3 (0.72 g, 2.2 mmol) were suspended in DMSO (12 mL), and the air was removed under vacuum for 15 min. The system was flushed with Ar, and 8-hydroxyquinoline (87 mg, 0.60 mmol) and copper iodide (0.49 g, 2.6 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 (70 mL), and the resulting suspension was stirred at ambient temperature for 30 min. The resulting solids were collected by filtration, dissolved in CH2Cl2 (30 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 (40 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 50:50 over 12 column volumes and held for 5 column volumes; increased to 0:100 over 10 column volumes and held for 5 column volumes) gave the title compound (0.51 g, 52%) as a yellow foam: 1H NMR (500 MHz, DMSO-d6) δ 8.00 (d, J=8.0 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.50-7.36 (m, 5H), 7.29 (d, J=8.0 Hz, 1H), 6.15 (dd, J=8.0, 2.5 Hz, 1H), 5.98 (d, J=2.5 Hz, 1H), 5.16 (s, 2H), 4.57 (s, 2H), 3.75 (t, J=5.5 Hz, 2H) 3.67 (s, 3H), 2.88 (t, J=5.5 Hz, 2H), 1.42 (s, 9H); ESI MS m/z 487 [M+H]+.

후처리

  1. customthe air was removed under vacuum for 15 min
  2. additionwere added to the suspension
  3. customThe evacuation/Ar flushing process
  4. temperatureThe mixture was cooled
  5. additiondiluted with 5.0:3.5:1.5 NH4Cl(aq.)/NH4OH/H2O (70 mL)
  6. filtrationThe resulting solids were collected by filtration
  7. dissolutiondissolved in CH2Cl2 (30 mL)
  8. washwashed with 5.0:3.5:1.5 NH4Cl(aq.)/NH4OH/H2O (2×30 mL)
  9. dry with materialThe resulting organic solution was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure
  12. temperatureFlash chromatography (40 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 50:50 over 12 column volumes and held for 5 column volumes; increased to 0:100 over 10 column volumes and held for 5 column volumes)

출처 및 근거

ORD 기록
ord-05690607def0486e98c63ea5479f7323
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993765B2

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