Nitrogen → tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

HRID 930609Notes

Reaction equation

HRID 930609 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12][C:7]=3[N:8]([CH3:11])[C:9]=2[CH:10]=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.[K+].[K+].OC1C=CC=C2C=1N=CC=C2.N#N>CS(C)=O.[Cu](I)I>[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][N:34]([C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12][C:7]=4[N:8]([CH3:11])[C:9]=3[CH:10]=2)[C:33](=[O:37])[CH:32]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 57950375tert-Butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Product 1

HCID 57950332tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylateYield 51.1%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

tert-Butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carbox-ylate (7.0 g, 19 mmol), 4-benzyloxypyridone (3.85 g, 19.2 mmol), K2CO3 (2.91 g, 21.1 mmol) and 8-hydroxyquinoline (418 mg, 2.88 mmol) were suspended in DMSO (50 mL) and the air removed under vacuum for 15 min. The system was then flushed with N2. This process was repeated and then copper iodide (547 mg, 2.88 mmol) was added. The evacuation/N2 flushing process was repeated twice more, and the reaction mixture was heated to 100-120° C. for 18 h. The mixture was cooled, partitioned between EtOAc and sat. NH4Cl and the organic phase removed, dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 100:0 to 98:2 to 95:5 to 92:8 then 90:10) gave the title compound (4.71 g, 51%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.50 (d, J=8.2 Hz, 1H), 7.43-7.35 (m, 5H), 7.32-7.29 (m, 2H), 7.01 (d, J=7.9 Hz, 1H), 6.10-6.03 (m, 2H), 5.06 (s, 2H), 4.64 (s, 2H), 3.89 (br t, 2H), 3.63 (s, 3H), 2.82 (br t, 2H), 1.50 (s, 9H).

Workup

  1. customthe air removed under vacuum for 15 min
  2. customThe system was then flushed with N2
  3. temperatureThe mixture was cooled
  4. custompartitioned between EtOAc and sat. NH4Cl
  5. customthe organic phase removed
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 100:0 to 98:2 to 95:5 to 92:8

Sources & evidence

ORD record
ord-d735b23d4792438c8861eb4db7172f52
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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