Cesium carbonate → (R)-4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)-5-methylmorpholin-3-one

HRID 1028968Notes

Reaction equation

HRID 1028968 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.C(C1CCCCC1=O)(=O)C(C)C.[CH3:35][C@H:36]1[NH:41][C:40](=[O:42])[CH2:39][O:38][CH2:37]1.C(=O)([O-])[O-].[Cs+].[Cs+]>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:41]1[C@H:36]([CH3:35])[CH2:37][O:38][CH2:39][C:40]1=[O:42])=[CH:5]2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-oneHCID 12400352(5R)-5-methylmorpholin-3-oneHCID 673456526-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine

Product 1

HCID 67325496(R)-4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)-5-methylmorpholin-3-one

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 (0.25 g, 0.533 mmol, prepared as in Example 1, Step 1-2), 2-isobutyrylcyclohexanone (0.018 g, 0.107 mmol), (R)-5-methylmorpholin-3-one (0.92 g, 7.99 mmol), copper(I) iodide (5.07 mg, 0.027 mmol), and cesium carbonate (0.35 g, 1.066 mmol) in DMF (5 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 7× 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 light yellow solid as (R)-4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)-5-methylmorpholin-3-one.

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-79244ae5ae83428fbbc44821b2e448d8
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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