Cesium carbonate → 6-bromo-3-(2-ethylmorpholino)-N-(4-methoxybenzyl)quinolin-2-amine

HRID 1028972Notes

Reaction equation

HRID 1028972 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:6](I)=[CH:5]2.[CH2:23]([CH:25]1[O:30][CH2:29][CH2:28][NH:27][CH2:26]1)[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+].C(C1CCCCC1=O)(=O)C(C)C>CN(C=O)C.[Cu]I>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:6]([N:27]1[CH2:28][CH2:29][O:30][CH:25]([CH2:23][CH3:24])[CH2:26]1)=[CH:5]2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-oneHCID 149332062-EthylmorpholineHCID 673456526-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine

Product 1

HCID 712532616-bromo-3-(2-ethylmorpholino)-N-(4-methoxybenzyl)quinolin-2-amine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 6-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine (0.30 g, 0.640 mmol, prepared as in Example 1, Step 1-2), 2-ethylmorpholine (1.105 g, 9.59 mmol), copper(I) iodide (6.09 mg, 0.032 mmol), cesium carbonate (0.417 g, 1.279 mmol), and 2-isobutyrylcyclohexanone (0.021 mL, 0.128 mmol) in DMF (3 mL) was heated at 125° C. for 10 min. Some product was observed but mostly starting material. The mixture was heated again at 125° C. for 10 min more. This process was repeated 3× until the starting material was completely consumed. The reaction was brought to RT, poured into water (20 mL) and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated, and chromatographed on silica gel using gradient 2:1 hexanes/EtOAc to afford a brown oil as 6-bromo-3-(2-ethylmorpholino)-N-(4-methoxybenzyl)quinolin-2-amine.

Workup

  1. temperatureThe mixture was heated again at 125° C. for 10 min more
  2. customwas completely consumed
  3. customwas brought to RT
  4. additionpoured into water (20 mL)
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed on silica gel using gradient 2:1 hexanes/EtOAc

Sources & evidence

ORD record
ord-25fb7f4caf964db3946e1685e7ddeeb0
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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