Methyl iodide → 4-(4-Bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methyl N-methylsulphonylamino)propoxy)quinazoline

HRID 454126Notes

Reaction equation

HRID 454126 reaction equation
[Br:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH2:22][NH:23][S:24]([CH3:27])(=[O:26])=[O:25])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:30])[CH:3]=1.[H-].[Na+].[CH3:33]I>CN(C=O)C>[Br:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH2:22][N:23]([CH3:33])[S:24]([CH3:27])(=[O:26])=[O:25])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:30])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 220307624-(4-bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methylsulphonylamino)propoxy)quinazoline

Product 1

HCID 220307614-(4-Bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methyl N-methylsulphonylamino)propoxy)quinazolineYield 83.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methylsulphonylamino)propoxy)quinazoline (1.0 g, 2 mmol) was taken up in DMF (10 ml), treated with sodium hydride (60% dispersion in mineral oil, 0.11 g, 2.7 mmol) and stirred, under nitrogen for 30 minutes. Methyl iodide (0.16 ml, 2.6 mmol) was added and the mixture stirred for 18 hours. The solvent was removed by evaporation and the residue taken up in water and extracted with dichloromethane (3×30 ml). The organic solution was then washed with water, brine, dried (MgSO4) and evaporated to dryness. The crude product was purified by silica column chromatography eluting with methanol (2.5 to 5%) in dichloromethane to give 4-(4-bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methyl N-methylsulphonylamino) propoxy)quinazoline (0.86 g, 83%).

Workup

  1. stirringthe mixture stirred for 18 hours
  2. customThe solvent was removed by evaporation
  3. extractionextracted with dichloromethane (3×30 ml)
  4. washThe organic solution was then washed with water, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to dryness
  7. customThe crude product was purified by silica column chromatography
  8. washeluting with methanol (2.5 to 5%) in dichloromethane

Sources & evidence

ORD record
ord-5e90d09b1b2e4adebb9d97df7fb5f0f6
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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