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

HRID 1020654Notes

Reaction equation

HRID 1020654 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20][CH2:19][C:7]=3[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si](C)(C)C)[C:9]=2[CH:10]=1.[CH2:30]([O:37][C:38]1[CH:43]=[CH:42][NH:41][C:40](=[O:44])[CH:39]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[CH2:30]([O:37][C:38]1[CH:43]=[CH:42][N:41]([C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20][CH2:19][C:7]=4[N:8]([CH2:11][O:12][CH2:13][CH3:14])[C:9]=3[CH:10]=2)[C:40](=[O:44])[CH:39]=1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 68658007tert-butyl 7-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Product 1

HCID 57950438tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-(ethoxymethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylateYield 14.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of tert-butyl 7-bromo-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.66 g, 1.9 mmol) in DMF (8 mL) was added NaH (60% weight dispersion in mineral oil, 113 mg, 2.82 mmol) followed by SEMCl (0.50 mL, 2.8 mmol). The reaction was stirred at room temperature until complete. The reaction was quenched with H2O, and the aqueous mixture was extracted with CH2Cl2. The organic phase was washed with H2O and brine and dried over Na2SO4. After filtration and concentration, the residue was dried under vacuum to give tert-butyl 7-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate, which and used directly in the next step. To a mixture of tert-butyl 7-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.75 g, 1.6 mmol), 4-benzyloxypyridone (0.31 g, 1.6 mmol), 8-hydroxyquilinine (34 mg, 0.23 mmol), K2CO3 (0.26 g, 1.9 mmol) and CuI (45 mg, 0.23 mmol) was added DMSO (6 mL). The reaction mixture was degassed and back-filled with N2. The reaction was stirred at 130° C. overnight. The mixture was cooled and filtered through a layer of Celite. The filtrate was diluted with CH2Cl2, washed with H2O and 5% aqueous LiCl and dried over Na2SO4. The organic solution was filtered and concentrated, and the residue was purified by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2) to give the title compound as a yellow oil (0.12 g, 13%): 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J=8.5 Hz, 1H), 7.44-7.37 (m, 6H), 7.31 (d, J=7.5 Hz, 1H), 7.09 (m, 1H), 6.12 (s, 1H), 6.07 (d, J=6.5 Hz, 1H), 5.40 (s, 2H), 5.07 (s, 2H), 4.65 (m, 2H), 3.86 (m, 2H), 3.51 (t, J=8.0 Hz, 2H), 2.73 (m, 2H), 1.53 (s, 9H), 0.89 (t, J=8.0 Hz, 2H), −0.04 (s, 9H); ESI MS m/z 602 [M+H]+.

Workup

  1. customThe reaction mixture was degassed
  2. additionback-filled with N2
  3. temperatureThe mixture was cooled
  4. filtrationfiltered through a layer of Celite
  5. additionThe filtrate was diluted with CH2Cl2
  6. washwashed with H2O and 5% aqueous LiCl
  7. dry with materialdried over Na2SO4
  8. filtrationThe organic solution was filtered
  9. concentrationconcentrated
  10. customthe residue was purified by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-960ec4c1951e456ebd5c5eb80a3c41f0
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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